Embryology - User contributions [en-gb]

User:Z3254758

2012-10-16T23:09:13Z

Z3254758: /* Lab Attendance */

==Lab Attendance==

--[[User:Z3254758|Z3254758]] 10:04, 25 July 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:35, 1 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:09, 8 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:04, 15 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:15, 22 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:05, 29 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 11:08, 12 September 2012 (EST) arrived at 10:10am

--[[User:Z3254758|Z3254758]] 10:02, 19 September 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:07, 26 September 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:11, 3 October 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:04, 10 October 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:09, 17 October 2012 (EST)

==Lab 1==

<pubmed>22178154</pubmed>

This article reviews some important features of capacitation as well as presenting their findings regarding the role of PLD-dependent actin polymerization in sperm motility during capacitation. They demonstrated the importance of PLD-dependent actin polymerization for developing hyper-activated motility.

==Lab 2==

{|
|-
|'''Task 1'''

|-
|[[File:Paternal_chromatin_mouse_embryos.jpg|thumb|left]]

|-
|'''Task 2'''

|-
|Rac1 and RhoA are Rho GTPases that regulate the invasion of the human embryo through the endometrial stroma. Inhibition of Rac1 expression prevents embryo invasion of the stroma, whereas inhibition of RhoA promotes it. Rac1 also plays a role in human endometrial stromal cell migration.

<pubmed>PMC2562412</pubmed>
|}

==Lab 3==

1. Gestational age refers to the time period between the first day of the mothers last period and birth. Fertilisation age is the time between conception and birth. <ref><pubmed>15520122</pubmed></ref>.

==Lab 4==

1.

Amniocentesis- involves using a needle to take a sample of amnitoic fluid. It can be used to detect down syndrome and turner syndrome among other abnormalities.

Chorionic villus sampling- a needle is used to take a sample of chorionic villus (placental tissue). It is helpful in detecting down syndrome and cystic fibrosis.

2.

<pubmed>3240835</pubmed>

This paper demonstrates the successful use of intrathecally injected mesenchymal cells derived from human umbilical cord blood to partially recanalise a dissected basilar artery. The patient was a 17 year old Korean man with infarction of the bilateral pons, midbrain and right superior cerebellum as a result of the basilar artery dissection.

The paper identifies that human umbilical cord blood contains hematopoietic stem cells, as well as mesenchymal stem cells which express neural makers Tuj1, TrkA, glial fibrillary acidic protein and cyclic nucleotide phosphodiesterases.

As a result of his condition the patient became quadriplegic, was unable to speak, and was unable to move his eyes, as well as a number of other symptoms. His clinical symptoms were visibly improved 5 days after the initial treatment with the mesenchymal cells. After the 27th day of treatment he regained his gag reflex, was able to swallow, had pupil dilation and was able to move his eyes, his soft palate stopped sagging, and the rigidity of his muscle tone reduced enough to allow him to sit in a wheelchair.

==Lab 7==

1.Provide a one sentence definition of a muscle satellite cell (b) In one paragraph, briefly discuss two examples of when satellite cells are activated ?

Satelite cells are stem cells that are located under the basal laminar of each muscle. When muscle is damaged satelite cells infiltrate the muscle and repair or replace it. They are normally quiescent.

2.In one brief paragraph, describe what happens to skeletal muscle fibre type and size when the innervating motor nerve sustains long term damage such as in spinal cord injury?

==Lab 8- Peer Review==

'''Group 2- Somatosensory'''

-Great introduction. Really puts the project in context and justifies the importance of your research. Citations need to be formatted like the rest of the page

-History of discoveries-very poor syntax, word repetition and no paragraphs. What is Weber's full name? This is entitled "history of discoveries" when it is actually just a very brief, nonspecific summary of "Weber". What about the other interesting discoveries from various scientists over decades?

-Adult Central Somatosensory systems- ascending in what? Position? Importance? Activity? Sensitivity? This needs a more informative opening sentence.

-Trigeminal system and Development of the Primary Somatosensory Cortex- are well explained and ideas are presented in a logical, flowing manner. Great picture with a good description and referencing (impressed you drew it).

-"making connections between...." what do the stages mean? Why does it start at stage 23 instead of stage 1?

-touch/touch receptors is good but where are the references?

-pain and pressure sections also good but needs paragraphs and the formatting of citations is incorrect

-bullet points in pressure section need a brief sentence introducing their purpose. Papers listed at bottom of section should be correctly cited instead of having hyperlinks

-interesting info in temperature

-current research- maybe you could put the name of the paper and authors and explain how they conducted their study? That would help with understanding the nice picture

-Glossary is incomplete

-Needs more pictures

-minor grammatical and spelling errors throughout but overall very good and well sequenced.

'''Group 3- Taste'''

Overall this is an excellent project. Well written, great informative photos, good use of tables, and comprehensive information that's well explained.

A few of the photos don't have the appropriate copyright information and some sections of text haven't been referenced, but in general this ticks all of the boxes

'''Group 4- olfaction'''

-numerous typos and syntax errors throughout. My favourite is "naval cavity"

-generally well explained and I like how you've used different formats for each section to keep it interesting

-this seems a bit random-

"SINUSES: A:
EFFECT OF AMNIOTIC FLUID ON THE DEVELOPMENT OF OLFACTION IN THE FETUS (current research in the field):"

-I think the anatomy section should come before the developmental timeline just to put the developmental stages in context

-abnormal function is very comprehensive :)

-current research is great, it appears some quality research went into this

-excellent use of resources throughout, including your external links. I think you've covered everything well

'''Group 5- abnormal vision'''

-content of introduction is good and immediately puts the page in context. Emphasises abnormal development. Perhaps reconsider the syntax of some of the sentences

-paragraphing throughout project needs review

-a picture near the beginning would make the page more engaging. Seeing you can't talk too much about normal eye development, it might help in conveying some information

-you frequently make use of the carnergie stages, which is great, but perhaps briefly describe what this system means

-it's good that you have contrasted normal and abnormal development for each structure, but make sure the information isn't repeated in the "normal development" section, or perhaps remove that section altogether

- info about what the different genes control is good. What does "the first embryonic days 8.5" mean?

-I assume the two separate sections in "ocular manifestations" are genetic and environmental, but because they're not stated in the intro of this section and there's so much information in-between, it's difficult to tell. The formatting of this section adds to the confusion. Keeping the information and formatting consistent for each abnormality will make this easier to follow. The appropriate heading, sub-heading etc formatting needs to be used as well

-I like your case study, it reminds us of how these problems effect real people

-no current research or external links section?

-excellent use of resources

'''Group 6-Hearing'''

-you had me at puppy

-good intro (a few typos) and history (I like your table)

-the start of adult anatomy and histology should have an opening sentence instead of just listing information. There is no histology?

-I'm guessing the heading for development is meant to be bigger instead of it appearing to be part of "adult anatomy and histology"? This section is very comprehensive!

-your "neural domain" drawing is a good way of explaining this concept

-the summary box is a great idea, but perhaps it should be entitled "Summary of inner ear development"

-I don't understand why this is present- "NOTE: DEFINITIONS OF SYNDROMIC AND NON SYNDROMIC HEARING LOSS". You have explained what non-syndromic hearing loss is in the 1 Mutation of GJB2 gene section, but as your note says, it might be good to have a brief section with these definitions

-your genetic and structural disease tables are nice but I feel that the formatting should be the same for all of the diseases, or you should explain why you've chosen to emphasise these abnormalities

-the PDF in the Toxoplasmosis section seems to have some good info, but should be formatted like the other references

-the references in the rubella, cytomegalovirus infection, drugs and technologies to detect sections need to be formatted properly. Some info in drugs section isn't referenced at all

-technologies to detect is not a very informative heading, you need to specify what you're detecting. The syntax in this section and "technologies to overcome the problems" is poor (including the headings)

-in text hyperlinks in current research section are good for making page more interactive

-you appear to have used a lot of great resources

==Lab 9 Assessment==

1. Identify and write a brief description of the findings of a recent research paper on development of one of the endocrine organs covered in today's practical.

<pubmed>21247964</pubmed>

The pituitary gland is derived from folds in the oral ectoderm and neural ectoderm. The homeodomain transcription factor, Vax1, is known to play a role in eye and optic chiasm development. This study showed that the absence of Vax1 causes an ectopic fold to form in the rostral oral ectoderm, eventually producing a second separate pituitary gland. This second gland has the same cell types and neuronal fibres as a normal pituitary gland.

The authors used Vax1 knockout mouse embryos in their experiment. Immunofluorescence, immunohistochemistry and in situ hybridization were utilised to obtain their results. Chromatin immunoprecipitation (ChIP) and reporter assays were used to process ventral forebrain tissue from the embryos.

2. Identify the embryonic layers and tissues that contribute to the developing teeth.

Ectoderm of the first pharyngeal arch and the ectomesenchyme from the neural crest.

== References ==
<references/>

User:Z3254758

2012-10-09T23:04:42Z

Z3254758: /* Lab Attendance */

==Lab Attendance==

--[[User:Z3254758|Z3254758]] 10:04, 25 July 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:35, 1 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:09, 8 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:04, 15 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:15, 22 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:05, 29 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 11:08, 12 September 2012 (EST) arrived at 10:10am

--[[User:Z3254758|Z3254758]] 10:02, 19 September 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:07, 26 September 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:11, 3 October 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:04, 10 October 2012 (EST)

==Lab 1==

<pubmed>22178154</pubmed>

This article reviews some important features of capacitation as well as presenting their findings regarding the role of PLD-dependent actin polymerization in sperm motility during capacitation. They demonstrated the importance of PLD-dependent actin polymerization for developing hyper-activated motility.

==Lab 2==

{|
|-
|'''Task 1'''

|-
|[[File:Paternal_chromatin_mouse_embryos.jpg|thumb|left]]

|-
|'''Task 2'''

|-
|Rac1 and RhoA are Rho GTPases that regulate the invasion of the human embryo through the endometrial stroma. Inhibition of Rac1 expression prevents embryo invasion of the stroma, whereas inhibition of RhoA promotes it. Rac1 also plays a role in human endometrial stromal cell migration.

<pubmed>PMC2562412</pubmed>
|}

==Lab 3==

1. Gestational age refers to the time period between the first day of the mothers last period and birth. Fertilisation age is the time between conception and birth. <ref><pubmed>15520122</pubmed></ref>.

==Lab 4==

1.

Amniocentesis- involves using a needle to take a sample of amnitoic fluid. It can be used to detect down syndrome and turner syndrome among other abnormalities.

Chorionic villus sampling- a needle is used to take a sample of chorionic villus (placental tissue). It is helpful in detecting down syndrome and cystic fibrosis.

2.

<pubmed>3240835</pubmed>

This paper demonstrates the successful use of intrathecally injected mesenchymal cells derived from human umbilical cord blood to partially recanalise a dissected basilar artery. The patient was a 17 year old Korean man with infarction of the bilateral pons, midbrain and right superior cerebellum as a result of the basilar artery dissection.

The paper identifies that human umbilical cord blood contains hematopoietic stem cells, as well as mesenchymal stem cells which express neural makers Tuj1, TrkA, glial fibrillary acidic protein and cyclic nucleotide phosphodiesterases.

As a result of his condition the patient became quadriplegic, was unable to speak, and was unable to move his eyes, as well as a number of other symptoms. His clinical symptoms were visibly improved 5 days after the initial treatment with the mesenchymal cells. After the 27th day of treatment he regained his gag reflex, was able to swallow, had pupil dilation and was able to move his eyes, his soft palate stopped sagging, and the rigidity of his muscle tone reduced enough to allow him to sit in a wheelchair.

==Lab 7==

1.Provide a one sentence definition of a muscle satellite cell (b) In one paragraph, briefly discuss two examples of when satellite cells are activated ?

Satelite cells are stem cells that are located under the basal laminar of each muscle. When muscle is damaged satelite cells infiltrate the muscle and repair or replace it. They are normally quiescent.

2.In one brief paragraph, describe what happens to skeletal muscle fibre type and size when the innervating motor nerve sustains long term damage such as in spinal cord injury?

==Lab 8- Peer Review==

'''Group 2- Somatosensory'''

-Great introduction. Really puts the project in context and justifies the importance of your research. Citations need to be formatted like the rest of the page

-History of discoveries-very poor syntax, word repetition and no paragraphs. What is Weber's full name? This is entitled "history of discoveries" when it is actually just a very brief, nonspecific summary of "Weber". What about the other interesting discoveries from various scientists over decades?

-Adult Central Somatosensory systems- ascending in what? Position? Importance? Activity? Sensitivity? This needs a more informative opening sentence.

-Trigeminal system and Development of the Primary Somatosensory Cortex- are well explained and ideas are presented in a logical, flowing manner. Great picture with a good description and referencing (impressed you drew it).

-"making connections between...." what do the stages mean? Why does it start at stage 23 instead of stage 1?

-touch/touch receptors is good but where are the references?

-pain and pressure sections also good but needs paragraphs and the formatting of citations is incorrect

-bullet points in pressure section need a brief sentence introducing their purpose. Papers listed at bottom of section should be correctly cited instead of having hyperlinks

-interesting info in temperature

-current research- maybe you could put the name of the paper and authors and explain how they conducted their study? That would help with understanding the nice picture

-Glossary is incomplete

-Needs more pictures

-minor grammatical and spelling errors throughout but overall very good and well sequenced.

'''Group 3- Taste'''

Overall this is an excellent project. Well written, great informative photos, good use of tables, and comprehensive information that's well explained.

A few of the photos don't have the appropriate copyright information and some sections of text haven't been referenced, but in general this ticks all of the boxes

'''Group 4- olfaction'''

-numerous typos and syntax errors throughout. My favourite is "naval cavity"

-generally well explained and I like how you've used different formats for each section to keep it interesting

-this seems a bit random-

"SINUSES: A:
EFFECT OF AMNIOTIC FLUID ON THE DEVELOPMENT OF OLFACTION IN THE FETUS (current research in the field):"

-I think the anatomy section should come before the developmental timeline just to put the developmental stages in context

-abnormal function is very comprehensive :)

-current research is great, it appears some quality research went into this

-excellent use of resources throughout, including your external links. I think you've covered everything well

'''Group 5- abnormal vision'''

-content of introduction is good and immediately puts the page in context. Emphasises abnormal development. Perhaps reconsider the syntax of some of the sentences

-paragraphing throughout project needs review

-a picture near the beginning would make the page more engaging. Seeing you can't talk too much about normal eye development, it might help in conveying some information

-you frequently make use of the carnergie stages, which is great, but perhaps briefly describe what this system means

-it's good that you have contrasted normal and abnormal development for each structure, but make sure the information isn't repeated in the "normal development" section, or perhaps remove that section altogether

- info about what the different genes control is good. What does "the first embryonic days 8.5" mean?

-I assume the two separate sections in "ocular manifestations" are genetic and environmental, but because they're not stated in the intro of this section and there's so much information in-between, it's difficult to tell. The formatting of this section adds to the confusion. Keeping the information and formatting consistent for each abnormality will make this easier to follow. The appropriate heading, sub-heading etc formatting needs to be used as well

-I like your case study, it reminds us of how these problems effect real people

-no current research or external links section?

-excellent use of resources

'''Group 6-Hearing'''

-you had me at puppy

-good intro (a few typos) and history (I like your table)

-the start of adult anatomy and histology should have an opening sentence instead of just listing information. There is no histology?

-I'm guessing the heading for development is meant to be bigger instead of it appearing to be part of "adult anatomy and histology"? This section is very comprehensive!

-your "neural domain" drawing is a good way of explaining this concept

-the summary box is a great idea, but perhaps it should be entitled "Summary of inner ear development"

-I don't understand why this is present- "NOTE: DEFINITIONS OF SYNDROMIC AND NON SYNDROMIC HEARING LOSS". You have explained what non-syndromic hearing loss is in the 1 Mutation of GJB2 gene section, but as your note says, it might be good to have a brief section with these definitions

-your genetic and structural disease tables are nice but I feel that the formatting should be the same for all of the diseases, or you should explain why you've chosen to emphasise these abnormalities

-the PDF in the Toxoplasmosis section seems to have some good info, but should be formatted like the other references

-the references in the rubella, cytomegalovirus infection, drugs and technologies to detect sections need to be formatted properly. Some info in drugs section isn't referenced at all

-technologies to detect is not a very informative heading, you need to specify what you're detecting. The syntax in this section and "technologies to overcome the problems" is poor (including the headings)

-in text hyperlinks in current research section are good for making page more interactive

-you appear to have used a lot of great resources

==Lab 9 Assessment==

1. Identify and write a brief description of the findings of a recent research paper on development of one of the endocrine organs covered in today's practical.

<pubmed>21247964</pubmed>

The pituitary gland is derived from folds in the oral ectoderm and neural ectoderm. The homeodomain transcription factor, Vax1, is known to play a role in eye and optic chiasm development. This study showed that the absence of Vax1 causes an ectopic fold to form in the rostral oral ectoderm, eventually producing a second separate pituitary gland. This second gland has the same cell types and neuronal fibres as a normal pituitary gland.

The authors used Vax1 knockout mouse embryos in their experiment. Immunofluorescence, immunohistochemistry and in situ hybridization were utilised to obtain their results. Chromatin immunoprecipitation (ChIP) and reporter assays were used to process ventral forebrain tissue from the embryos.

2. Identify the embryonic layers and tissues that contribute to the developing teeth.

Ectoderm of the first pharyngeal arch and the ectomesenchyme from the neural crest.

== References ==
<references/>

User:Z3254758

2012-10-09T22:22:13Z

Z3254758: /* Lab 9 Assessment */

==Lab Attendance==

--[[User:Z3254758|Z3254758]] 10:04, 25 July 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:35, 1 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:09, 8 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:04, 15 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:15, 22 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:05, 29 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 11:08, 12 September 2012 (EST) arrived at 10:10am

--[[User:Z3254758|Z3254758]] 10:02, 19 September 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:07, 26 September 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:11, 3 October 2012 (EST)

==Lab 1==

<pubmed>22178154</pubmed>

This article reviews some important features of capacitation as well as presenting their findings regarding the role of PLD-dependent actin polymerization in sperm motility during capacitation. They demonstrated the importance of PLD-dependent actin polymerization for developing hyper-activated motility.

==Lab 2==

{|
|-
|'''Task 1'''

|-
|[[File:Paternal_chromatin_mouse_embryos.jpg|thumb|left]]

|-
|'''Task 2'''

|-
|Rac1 and RhoA are Rho GTPases that regulate the invasion of the human embryo through the endometrial stroma. Inhibition of Rac1 expression prevents embryo invasion of the stroma, whereas inhibition of RhoA promotes it. Rac1 also plays a role in human endometrial stromal cell migration.

<pubmed>PMC2562412</pubmed>
|}

==Lab 3==

1. Gestational age refers to the time period between the first day of the mothers last period and birth. Fertilisation age is the time between conception and birth. <ref><pubmed>15520122</pubmed></ref>.

==Lab 4==

1.

Amniocentesis- involves using a needle to take a sample of amnitoic fluid. It can be used to detect down syndrome and turner syndrome among other abnormalities.

Chorionic villus sampling- a needle is used to take a sample of chorionic villus (placental tissue). It is helpful in detecting down syndrome and cystic fibrosis.

2.

<pubmed>3240835</pubmed>

This paper demonstrates the successful use of intrathecally injected mesenchymal cells derived from human umbilical cord blood to partially recanalise a dissected basilar artery. The patient was a 17 year old Korean man with infarction of the bilateral pons, midbrain and right superior cerebellum as a result of the basilar artery dissection.

The paper identifies that human umbilical cord blood contains hematopoietic stem cells, as well as mesenchymal stem cells which express neural makers Tuj1, TrkA, glial fibrillary acidic protein and cyclic nucleotide phosphodiesterases.

As a result of his condition the patient became quadriplegic, was unable to speak, and was unable to move his eyes, as well as a number of other symptoms. His clinical symptoms were visibly improved 5 days after the initial treatment with the mesenchymal cells. After the 27th day of treatment he regained his gag reflex, was able to swallow, had pupil dilation and was able to move his eyes, his soft palate stopped sagging, and the rigidity of his muscle tone reduced enough to allow him to sit in a wheelchair.

==Lab 7==

1.Provide a one sentence definition of a muscle satellite cell (b) In one paragraph, briefly discuss two examples of when satellite cells are activated ?

Satelite cells are stem cells that are located under the basal laminar of each muscle. When muscle is damaged satelite cells infiltrate the muscle and repair or replace it. They are normally quiescent.

2.In one brief paragraph, describe what happens to skeletal muscle fibre type and size when the innervating motor nerve sustains long term damage such as in spinal cord injury?

==Lab 8- Peer Review==

'''Group 2- Somatosensory'''

-Great introduction. Really puts the project in context and justifies the importance of your research. Citations need to be formatted like the rest of the page

-History of discoveries-very poor syntax, word repetition and no paragraphs. What is Weber's full name? This is entitled "history of discoveries" when it is actually just a very brief, nonspecific summary of "Weber". What about the other interesting discoveries from various scientists over decades?

-Adult Central Somatosensory systems- ascending in what? Position? Importance? Activity? Sensitivity? This needs a more informative opening sentence.

-Trigeminal system and Development of the Primary Somatosensory Cortex- are well explained and ideas are presented in a logical, flowing manner. Great picture with a good description and referencing (impressed you drew it).

-"making connections between...." what do the stages mean? Why does it start at stage 23 instead of stage 1?

-touch/touch receptors is good but where are the references?

-pain and pressure sections also good but needs paragraphs and the formatting of citations is incorrect

-bullet points in pressure section need a brief sentence introducing their purpose. Papers listed at bottom of section should be correctly cited instead of having hyperlinks

-interesting info in temperature

-current research- maybe you could put the name of the paper and authors and explain how they conducted their study? That would help with understanding the nice picture

-Glossary is incomplete

-Needs more pictures

-minor grammatical and spelling errors throughout but overall very good and well sequenced.

'''Group 3- Taste'''

Overall this is an excellent project. Well written, great informative photos, good use of tables, and comprehensive information that's well explained.

A few of the photos don't have the appropriate copyright information and some sections of text haven't been referenced, but in general this ticks all of the boxes

'''Group 4- olfaction'''

-numerous typos and syntax errors throughout. My favourite is "naval cavity"

-generally well explained and I like how you've used different formats for each section to keep it interesting

-this seems a bit random-

"SINUSES: A:
EFFECT OF AMNIOTIC FLUID ON THE DEVELOPMENT OF OLFACTION IN THE FETUS (current research in the field):"

-I think the anatomy section should come before the developmental timeline just to put the developmental stages in context

-abnormal function is very comprehensive :)

-current research is great, it appears some quality research went into this

-excellent use of resources throughout, including your external links. I think you've covered everything well

'''Group 5- abnormal vision'''

-content of introduction is good and immediately puts the page in context. Emphasises abnormal development. Perhaps reconsider the syntax of some of the sentences

-paragraphing throughout project needs review

-a picture near the beginning would make the page more engaging. Seeing you can't talk too much about normal eye development, it might help in conveying some information

-you frequently make use of the carnergie stages, which is great, but perhaps briefly describe what this system means

-it's good that you have contrasted normal and abnormal development for each structure, but make sure the information isn't repeated in the "normal development" section, or perhaps remove that section altogether

- info about what the different genes control is good. What does "the first embryonic days 8.5" mean?

-I assume the two separate sections in "ocular manifestations" are genetic and environmental, but because they're not stated in the intro of this section and there's so much information in-between, it's difficult to tell. The formatting of this section adds to the confusion. Keeping the information and formatting consistent for each abnormality will make this easier to follow. The appropriate heading, sub-heading etc formatting needs to be used as well

-I like your case study, it reminds us of how these problems effect real people

-no current research or external links section?

-excellent use of resources

'''Group 6-Hearing'''

-you had me at puppy

-good intro (a few typos) and history (I like your table)

-the start of adult anatomy and histology should have an opening sentence instead of just listing information. There is no histology?

-I'm guessing the heading for development is meant to be bigger instead of it appearing to be part of "adult anatomy and histology"? This section is very comprehensive!

-your "neural domain" drawing is a good way of explaining this concept

-the summary box is a great idea, but perhaps it should be entitled "Summary of inner ear development"

-I don't understand why this is present- "NOTE: DEFINITIONS OF SYNDROMIC AND NON SYNDROMIC HEARING LOSS". You have explained what non-syndromic hearing loss is in the 1 Mutation of GJB2 gene section, but as your note says, it might be good to have a brief section with these definitions

-your genetic and structural disease tables are nice but I feel that the formatting should be the same for all of the diseases, or you should explain why you've chosen to emphasise these abnormalities

-the PDF in the Toxoplasmosis section seems to have some good info, but should be formatted like the other references

-the references in the rubella, cytomegalovirus infection, drugs and technologies to detect sections need to be formatted properly. Some info in drugs section isn't referenced at all

-technologies to detect is not a very informative heading, you need to specify what you're detecting. The syntax in this section and "technologies to overcome the problems" is poor (including the headings)

-in text hyperlinks in current research section are good for making page more interactive

-you appear to have used a lot of great resources

==Lab 9 Assessment==

1. Identify and write a brief description of the findings of a recent research paper on development of one of the endocrine organs covered in today's practical.

<pubmed>21247964</pubmed>

The pituitary gland is derived from folds in the oral ectoderm and neural ectoderm. The homeodomain transcription factor, Vax1, is known to play a role in eye and optic chiasm development. This study showed that the absence of Vax1 causes an ectopic fold to form in the rostral oral ectoderm, eventually producing a second separate pituitary gland. This second gland has the same cell types and neuronal fibres as a normal pituitary gland.

The authors used Vax1 knockout mouse embryos in their experiment. Immunofluorescence, immunohistochemistry and in situ hybridization were utilised to obtain their results. Chromatin immunoprecipitation (ChIP) and reporter assays were used to process ventral forebrain tissue from the embryos.

2. Identify the embryonic layers and tissues that contribute to the developing teeth.

Ectoderm of the first pharyngeal arch and the ectomesenchyme from the neural crest.

== References ==
<references/>

User:Z3254758

2012-10-09T22:18:42Z

Z3254758: /* Lab 9 Assessment */

==Lab Attendance==

--[[User:Z3254758|Z3254758]] 10:04, 25 July 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:35, 1 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:09, 8 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:04, 15 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:15, 22 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:05, 29 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 11:08, 12 September 2012 (EST) arrived at 10:10am

--[[User:Z3254758|Z3254758]] 10:02, 19 September 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:07, 26 September 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:11, 3 October 2012 (EST)

==Lab 1==

<pubmed>22178154</pubmed>

This article reviews some important features of capacitation as well as presenting their findings regarding the role of PLD-dependent actin polymerization in sperm motility during capacitation. They demonstrated the importance of PLD-dependent actin polymerization for developing hyper-activated motility.

==Lab 2==

{|
|-
|'''Task 1'''

|-
|[[File:Paternal_chromatin_mouse_embryos.jpg|thumb|left]]

|-
|'''Task 2'''

|-
|Rac1 and RhoA are Rho GTPases that regulate the invasion of the human embryo through the endometrial stroma. Inhibition of Rac1 expression prevents embryo invasion of the stroma, whereas inhibition of RhoA promotes it. Rac1 also plays a role in human endometrial stromal cell migration.

<pubmed>PMC2562412</pubmed>
|}

==Lab 3==

1. Gestational age refers to the time period between the first day of the mothers last period and birth. Fertilisation age is the time between conception and birth. <ref><pubmed>15520122</pubmed></ref>.

==Lab 4==

1.

Amniocentesis- involves using a needle to take a sample of amnitoic fluid. It can be used to detect down syndrome and turner syndrome among other abnormalities.

Chorionic villus sampling- a needle is used to take a sample of chorionic villus (placental tissue). It is helpful in detecting down syndrome and cystic fibrosis.

2.

<pubmed>3240835</pubmed>

This paper demonstrates the successful use of intrathecally injected mesenchymal cells derived from human umbilical cord blood to partially recanalise a dissected basilar artery. The patient was a 17 year old Korean man with infarction of the bilateral pons, midbrain and right superior cerebellum as a result of the basilar artery dissection.

The paper identifies that human umbilical cord blood contains hematopoietic stem cells, as well as mesenchymal stem cells which express neural makers Tuj1, TrkA, glial fibrillary acidic protein and cyclic nucleotide phosphodiesterases.

As a result of his condition the patient became quadriplegic, was unable to speak, and was unable to move his eyes, as well as a number of other symptoms. His clinical symptoms were visibly improved 5 days after the initial treatment with the mesenchymal cells. After the 27th day of treatment he regained his gag reflex, was able to swallow, had pupil dilation and was able to move his eyes, his soft palate stopped sagging, and the rigidity of his muscle tone reduced enough to allow him to sit in a wheelchair.

==Lab 7==

1.Provide a one sentence definition of a muscle satellite cell (b) In one paragraph, briefly discuss two examples of when satellite cells are activated ?

Satelite cells are stem cells that are located under the basal laminar of each muscle. When muscle is damaged satelite cells infiltrate the muscle and repair or replace it. They are normally quiescent.

2.In one brief paragraph, describe what happens to skeletal muscle fibre type and size when the innervating motor nerve sustains long term damage such as in spinal cord injury?

==Lab 8- Peer Review==

'''Group 2- Somatosensory'''

-Great introduction. Really puts the project in context and justifies the importance of your research. Citations need to be formatted like the rest of the page

-History of discoveries-very poor syntax, word repetition and no paragraphs. What is Weber's full name? This is entitled "history of discoveries" when it is actually just a very brief, nonspecific summary of "Weber". What about the other interesting discoveries from various scientists over decades?

-Adult Central Somatosensory systems- ascending in what? Position? Importance? Activity? Sensitivity? This needs a more informative opening sentence.

-Trigeminal system and Development of the Primary Somatosensory Cortex- are well explained and ideas are presented in a logical, flowing manner. Great picture with a good description and referencing (impressed you drew it).

-"making connections between...." what do the stages mean? Why does it start at stage 23 instead of stage 1?

-touch/touch receptors is good but where are the references?

-pain and pressure sections also good but needs paragraphs and the formatting of citations is incorrect

-bullet points in pressure section need a brief sentence introducing their purpose. Papers listed at bottom of section should be correctly cited instead of having hyperlinks

-interesting info in temperature

-current research- maybe you could put the name of the paper and authors and explain how they conducted their study? That would help with understanding the nice picture

-Glossary is incomplete

-Needs more pictures

-minor grammatical and spelling errors throughout but overall very good and well sequenced.

'''Group 3- Taste'''

Overall this is an excellent project. Well written, great informative photos, good use of tables, and comprehensive information that's well explained.

A few of the photos don't have the appropriate copyright information and some sections of text haven't been referenced, but in general this ticks all of the boxes

'''Group 4- olfaction'''

-numerous typos and syntax errors throughout. My favourite is "naval cavity"

-generally well explained and I like how you've used different formats for each section to keep it interesting

-this seems a bit random-

"SINUSES: A:
EFFECT OF AMNIOTIC FLUID ON THE DEVELOPMENT OF OLFACTION IN THE FETUS (current research in the field):"

-I think the anatomy section should come before the developmental timeline just to put the developmental stages in context

-abnormal function is very comprehensive :)

-current research is great, it appears some quality research went into this

-excellent use of resources throughout, including your external links. I think you've covered everything well

'''Group 5- abnormal vision'''

-content of introduction is good and immediately puts the page in context. Emphasises abnormal development. Perhaps reconsider the syntax of some of the sentences

-paragraphing throughout project needs review

-a picture near the beginning would make the page more engaging. Seeing you can't talk too much about normal eye development, it might help in conveying some information

-you frequently make use of the carnergie stages, which is great, but perhaps briefly describe what this system means

-it's good that you have contrasted normal and abnormal development for each structure, but make sure the information isn't repeated in the "normal development" section, or perhaps remove that section altogether

- info about what the different genes control is good. What does "the first embryonic days 8.5" mean?

-I assume the two separate sections in "ocular manifestations" are genetic and environmental, but because they're not stated in the intro of this section and there's so much information in-between, it's difficult to tell. The formatting of this section adds to the confusion. Keeping the information and formatting consistent for each abnormality will make this easier to follow. The appropriate heading, sub-heading etc formatting needs to be used as well

-I like your case study, it reminds us of how these problems effect real people

-no current research or external links section?

-excellent use of resources

'''Group 6-Hearing'''

-you had me at puppy

-good intro (a few typos) and history (I like your table)

-the start of adult anatomy and histology should have an opening sentence instead of just listing information. There is no histology?

-I'm guessing the heading for development is meant to be bigger instead of it appearing to be part of "adult anatomy and histology"? This section is very comprehensive!

-your "neural domain" drawing is a good way of explaining this concept

-the summary box is a great idea, but perhaps it should be entitled "Summary of inner ear development"

-I don't understand why this is present- "NOTE: DEFINITIONS OF SYNDROMIC AND NON SYNDROMIC HEARING LOSS". You have explained what non-syndromic hearing loss is in the 1 Mutation of GJB2 gene section, but as your note says, it might be good to have a brief section with these definitions

-your genetic and structural disease tables are nice but I feel that the formatting should be the same for all of the diseases, or you should explain why you've chosen to emphasise these abnormalities

-the PDF in the Toxoplasmosis section seems to have some good info, but should be formatted like the other references

-the references in the rubella, cytomegalovirus infection, drugs and technologies to detect sections need to be formatted properly. Some info in drugs section isn't referenced at all

-technologies to detect is not a very informative heading, you need to specify what you're detecting. The syntax in this section and "technologies to overcome the problems" is poor (including the headings)

-in text hyperlinks in current research section are good for making page more interactive

-you appear to have used a lot of great resources

==Lab 9 Assessment==

1. Identify and write a brief description of the findings of a recent research paper on development of one of the endocrine organs covered in today's practical.

<pubmed>21247964</pubmed>

The pituitary gland is derived from folds in the oral ectoderm and neural ectoderm. The homeodomain transcription factor, Vax1, is known to play a role in eye and optic chiasm development. This study showed that the absence of Vax1 causes an ectopic fold to form in the rostral oral ectoderm, eventually producing a second separate pituitary gland. This second gland has the same cell types and neuronal fibres as a normal pituitary gland.

The authors used Vax1 knockout mouse embryos in their experiment. Immunofluorescence, immunohistochemistry and in situ hybridization were utilised to obtain their results. Chromatin immunoprecipitation (ChIP) and reporter assays were used to process ventral forebrain tissue from the embryos.

2. Identify the embryonic layers and tissues that contribute to the developing teeth.

== References ==
<references/>

User:Z3254758

2012-10-09T21:58:15Z

Z3254758: /* Lab 8- Peer Review */

==Lab Attendance==

--[[User:Z3254758|Z3254758]] 10:04, 25 July 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:35, 1 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:09, 8 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:04, 15 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:15, 22 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:05, 29 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 11:08, 12 September 2012 (EST) arrived at 10:10am

--[[User:Z3254758|Z3254758]] 10:02, 19 September 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:07, 26 September 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:11, 3 October 2012 (EST)

==Lab 1==

<pubmed>22178154</pubmed>

This article reviews some important features of capacitation as well as presenting their findings regarding the role of PLD-dependent actin polymerization in sperm motility during capacitation. They demonstrated the importance of PLD-dependent actin polymerization for developing hyper-activated motility.

==Lab 2==

{|
|-
|'''Task 1'''

|-
|[[File:Paternal_chromatin_mouse_embryos.jpg|thumb|left]]

|-
|'''Task 2'''

|-
|Rac1 and RhoA are Rho GTPases that regulate the invasion of the human embryo through the endometrial stroma. Inhibition of Rac1 expression prevents embryo invasion of the stroma, whereas inhibition of RhoA promotes it. Rac1 also plays a role in human endometrial stromal cell migration.

<pubmed>PMC2562412</pubmed>
|}

==Lab 3==

1. Gestational age refers to the time period between the first day of the mothers last period and birth. Fertilisation age is the time between conception and birth. <ref><pubmed>15520122</pubmed></ref>.

==Lab 4==

1.

Amniocentesis- involves using a needle to take a sample of amnitoic fluid. It can be used to detect down syndrome and turner syndrome among other abnormalities.

Chorionic villus sampling- a needle is used to take a sample of chorionic villus (placental tissue). It is helpful in detecting down syndrome and cystic fibrosis.

2.

<pubmed>3240835</pubmed>

This paper demonstrates the successful use of intrathecally injected mesenchymal cells derived from human umbilical cord blood to partially recanalise a dissected basilar artery. The patient was a 17 year old Korean man with infarction of the bilateral pons, midbrain and right superior cerebellum as a result of the basilar artery dissection.

The paper identifies that human umbilical cord blood contains hematopoietic stem cells, as well as mesenchymal stem cells which express neural makers Tuj1, TrkA, glial fibrillary acidic protein and cyclic nucleotide phosphodiesterases.

As a result of his condition the patient became quadriplegic, was unable to speak, and was unable to move his eyes, as well as a number of other symptoms. His clinical symptoms were visibly improved 5 days after the initial treatment with the mesenchymal cells. After the 27th day of treatment he regained his gag reflex, was able to swallow, had pupil dilation and was able to move his eyes, his soft palate stopped sagging, and the rigidity of his muscle tone reduced enough to allow him to sit in a wheelchair.

==Lab 7==

1.Provide a one sentence definition of a muscle satellite cell (b) In one paragraph, briefly discuss two examples of when satellite cells are activated ?

Satelite cells are stem cells that are located under the basal laminar of each muscle. When muscle is damaged satelite cells infiltrate the muscle and repair or replace it. They are normally quiescent.

2.In one brief paragraph, describe what happens to skeletal muscle fibre type and size when the innervating motor nerve sustains long term damage such as in spinal cord injury?

==Lab 8- Peer Review==

'''Group 2- Somatosensory'''

-Great introduction. Really puts the project in context and justifies the importance of your research. Citations need to be formatted like the rest of the page

-History of discoveries-very poor syntax, word repetition and no paragraphs. What is Weber's full name? This is entitled "history of discoveries" when it is actually just a very brief, nonspecific summary of "Weber". What about the other interesting discoveries from various scientists over decades?

-Adult Central Somatosensory systems- ascending in what? Position? Importance? Activity? Sensitivity? This needs a more informative opening sentence.

-Trigeminal system and Development of the Primary Somatosensory Cortex- are well explained and ideas are presented in a logical, flowing manner. Great picture with a good description and referencing (impressed you drew it).

-"making connections between...." what do the stages mean? Why does it start at stage 23 instead of stage 1?

-touch/touch receptors is good but where are the references?

-pain and pressure sections also good but needs paragraphs and the formatting of citations is incorrect

-bullet points in pressure section need a brief sentence introducing their purpose. Papers listed at bottom of section should be correctly cited instead of having hyperlinks

-interesting info in temperature

-current research- maybe you could put the name of the paper and authors and explain how they conducted their study? That would help with understanding the nice picture

-Glossary is incomplete

-Needs more pictures

-minor grammatical and spelling errors throughout but overall very good and well sequenced.

'''Group 3- Taste'''

Overall this is an excellent project. Well written, great informative photos, good use of tables, and comprehensive information that's well explained.

A few of the photos don't have the appropriate copyright information and some sections of text haven't been referenced, but in general this ticks all of the boxes

'''Group 4- olfaction'''

-numerous typos and syntax errors throughout. My favourite is "naval cavity"

-generally well explained and I like how you've used different formats for each section to keep it interesting

-this seems a bit random-

"SINUSES: A:
EFFECT OF AMNIOTIC FLUID ON THE DEVELOPMENT OF OLFACTION IN THE FETUS (current research in the field):"

-I think the anatomy section should come before the developmental timeline just to put the developmental stages in context

-abnormal function is very comprehensive :)

-current research is great, it appears some quality research went into this

-excellent use of resources throughout, including your external links. I think you've covered everything well

'''Group 5- abnormal vision'''

-content of introduction is good and immediately puts the page in context. Emphasises abnormal development. Perhaps reconsider the syntax of some of the sentences

-paragraphing throughout project needs review

-a picture near the beginning would make the page more engaging. Seeing you can't talk too much about normal eye development, it might help in conveying some information

-you frequently make use of the carnergie stages, which is great, but perhaps briefly describe what this system means

-it's good that you have contrasted normal and abnormal development for each structure, but make sure the information isn't repeated in the "normal development" section, or perhaps remove that section altogether

- info about what the different genes control is good. What does "the first embryonic days 8.5" mean?

-I assume the two separate sections in "ocular manifestations" are genetic and environmental, but because they're not stated in the intro of this section and there's so much information in-between, it's difficult to tell. The formatting of this section adds to the confusion. Keeping the information and formatting consistent for each abnormality will make this easier to follow. The appropriate heading, sub-heading etc formatting needs to be used as well

-I like your case study, it reminds us of how these problems effect real people

-no current research or external links section?

-excellent use of resources

'''Group 6-Hearing'''

-you had me at puppy

-good intro (a few typos) and history (I like your table)

-the start of adult anatomy and histology should have an opening sentence instead of just listing information. There is no histology?

-I'm guessing the heading for development is meant to be bigger instead of it appearing to be part of "adult anatomy and histology"? This section is very comprehensive!

-your "neural domain" drawing is a good way of explaining this concept

-the summary box is a great idea, but perhaps it should be entitled "Summary of inner ear development"

-I don't understand why this is present- "NOTE: DEFINITIONS OF SYNDROMIC AND NON SYNDROMIC HEARING LOSS". You have explained what non-syndromic hearing loss is in the 1 Mutation of GJB2 gene section, but as your note says, it might be good to have a brief section with these definitions

-your genetic and structural disease tables are nice but I feel that the formatting should be the same for all of the diseases, or you should explain why you've chosen to emphasise these abnormalities

-the PDF in the Toxoplasmosis section seems to have some good info, but should be formatted like the other references

-the references in the rubella, cytomegalovirus infection, drugs and technologies to detect sections need to be formatted properly. Some info in drugs section isn't referenced at all

-technologies to detect is not a very informative heading, you need to specify what you're detecting. The syntax in this section and "technologies to overcome the problems" is poor (including the headings)

-in text hyperlinks in current research section are good for making page more interactive

-you appear to have used a lot of great resources

==Lab 9 Assessment==

1. Identify and write a brief description of the findings of a recent research paper on development of one of the endocrine organs covered in today's practical.
2. Identify the embryonic layers and tissues that contribute to the developing teeth.

== References ==
<references/>

2012 Group Project 1

2012-10-03T01:54:35Z

Z3254758: /* Glossary */

[[File:Eye_collage_2.jpg|right|830px]]

=Vision Development=

==Introduction==

Eyes are an important sensory organ shared across many different species and allow organisms to gather useful visual information from their environment. The visual system uses light from the environment and processes this information in the brain for visual perception. The visual system is complex, and is made up of various structures that work together to form vision. Each of the structures in the eye have specific tasks which contribute to the visual system. Knowledge of how the eye develops extends as far back as Aristotle more than 2000 years ago, and current knowledge shows that most of the crucial events of eye development occur in the embryological stage. The eye is an interesting model for studying the development of tissues in organisms, as it consists of cells from several parts of the embryo including the head ectoderm, neural ectoderm and mesoderm. From its many origins the cells come together and differentiate to produce the complex organ that is the eye. During this period there are many examples of inductive signaling, as the tissues coordinate their development throughout this elegant process.

The main anatomical structures of the eye are as follows:
{|
|
* Cornea

* Sclera

* Choroid

* Iris

* Ciliary body

* Lens

* Anterior chamber

* Posterior chamber

* Retina

* Optic nerve

|[[File:eye_diagram_bandw.jpg|right|250px|thumb|Basic structure of the human eye.]]
|[[File:Eye-pupil-sclera-iris.jpg|thumbnail|200px|Illustration of the front of the eye, showing the sclera, iris and pupil.]]
|}
[[File:Eyediagramcolour1.JPG|550px]]

==Research History==

=== '''Brief Timeline of Historical Developments on the Eye and its Embryology''' ===

{| width=800px
|-bgcolor="CEDFF2"
| width=100px|'''Time'''
| width=700px|'''Discovery'''

|-bgcolor="F5FAFF"
| '''Ancient Egyptians'''
| First to document cataracts. It is described as being 'the white disease of the eye' or 'darkening of the pupil.' <ref>Edwards, D.D. (1996). Ophthalmology before Hippocrates. In the History of Ophthalmology, ed. D.M. Albert and D.D. Edwards. Cambridge, Mass.: Blackwell Science.</ref> The Egyptians had some knowledge of the eye, however it is not known how much of the anatomy of the eye was known in their era.

|-bgcolor="CEDFF2"
| '''535 BC'''

|
Ancient Greek philosopher Alcmaeon conducted dissection of humans for the first time in recorded history. This included dissection of the eye. However, not much is known about which anatomical features he discovered. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17.">Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17.</ref>

|-bgcolor="F5FAFF"
| '''384- 322 BC'''

| [[File:Aristotle-eye.jpg|200px|thumbnail|The eye according to Aristotle.<ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "> Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau </ref> Note the lens is missing, and there are three vessels drawn that was believed to transport fluid to and from the eye.<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
]]
Aristotle performed dissections of animal embryos.<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

When Aristotle described the embryo of a ten day old chicken, he wrote "The eyes about this time, if taken out, are larger than beans and black; if their skin is removed the fluid inside is white and cold, shining brightly in the light, but nothing solid." <ref name="Magnus, H. (1998). Ophthalmology of the ancients. In J. Hirschberg (Ed.), The History of Ophthalmology: The monographs, Vol. 4, Part 1 (F.C. Blodi, Trans.) Bonn: Wayenborgh.">Magnus, H. (1998). Ophthalmology of the ancients. In J. Hirschberg (Ed.), The History of Ophthalmology: The monographs, Vol. 4, Part 1 (F.C. Blodi, Trans.) Bonn: Wayenborgh.</ref>

Aristotle believed that the eyes started forming during early embryogenesis, however, he also believed that the eyes are the last organs to form completely, and he incorrectly thought that the eyes shrink in later embryonic development. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press.">Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press.</ref> .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"

| '''340 BC'''

| Lens is thought to have been discovered by Hippocrates, due to his descriptions of the contents of the internal eye There has been studies in chick development later on by followers of Hippocrates. They claimed that eyes were visible in early embryogenesis. .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
|-bgcolor="F5FAFF"
|'''25 BC - 50 AD'''

| [[File:Celsus-eye.jpg|150px|thumb|The eye according to Celsus. <ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "/>
Note the lens is placed in the centre of the eye, in the vitreous.<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> ]]

Aulus Cornelius Celsus wrote a Roman medical text called 'De Medicina' in which he wrote that the lens was the part of the eye from which vision originated. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.">Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.</ref> Celsus also incorrectly drew the lens in the center of the globe in his diagram of the eye. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

|-bgcolor="CEDFF2"
| '''23-79 AD '''
|
Pliny the Elder said that the eye is the last of the organs to develop in the womb <ref name="Magnus, H. (1998). Ophthalmology of the ancients. In J. Hirschberg (Ed.), The History of Ophthalmology: The monographs, Vol. 4, Part 1 (F.C. Blodi, Trans.) Bonn: Wayenborgh."/>
|-bgcolor="F5FAFF"
| '''98-117 AD'''

| [[File:Rufus-eye.jpg|150px|thumb|The eye according to Rufus of Ephesus. <ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "/>
Note the lens is placed in the correct position, behind the iris of the eye <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> ]]

Rufus of Ephesus identified the lens as being located in the anterior part of the eye, close to the pupil. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

His diagram illustrates that he knew the correct position of the lens as being directly behind the iris, in the anterior part of the eye, and not in the centre as was previously depicted by others before him.

|-bgcolor="CEDFF2"
| '''130-200 AD'''

| [[File:Galen-eye1.jpg|150px|thumb|The eye according to Galen. <ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "/> ]]

Claudius Galen practised medicine in Rome. He wrote:

"1. Within the eye the principal orgran of sensation is the crystalline lens.

2. The sensation potential comes from the brain and is conducted via the optic nerves.

3. All other parts of the eyeball are supporting structures." <ref> Hirschberge, J. (1982). Antiquity, Vol. X in the History of Ophthalmology (F.C. Blodi, Trans.) Bonn: Wayenborgh. pp. 280 </ref>

Galen thought that the lens was produced from the vitreous. He also believed that the retina’s function was to give nourishment to the lens and vitreous, and to carry visual information to the brain from the lens. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

|-bgcolor="F5FAFF"

| '''1514-1564'''

| Andreas Vesalius published his anatomy book "De Humani Corporis Fabrica in 1543. He had the misconception that the lens was located in the centre of the eyeball. .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> He also wrote that the lens functioned "like a convex lens made of glass" <ref name="Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.">Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.</ref> pp. 48
|-bgcolor="CEDFF2"
| '''1535-1606'''

| Georg Bartisch correctly drew a diagram of the lens placed behind the iris in his book 'Ophthalmodouleia: das ist Augendienst'. <ref name="Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>
|-bgcolor="F5FAFF"

| '''1537-1619'''

| Fallopio Hieronymus Fabricius ab Aquapendente studied anatomy and embryology. He studied chicken embryos, and thought that chalazae (which comes from egg white) gives rise to the eyes. He also drew the lens directly behind the iris in a diagram in is book 'Tractatus de Oculo Visuque Organo. <ref name="Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

|-bgcolor="CEDFF2"
| '''1583'''

| Felix Platter published his book 'De corporis Humani Structura et Usu, after he performed dissections of human bodies. He believed that the retina is the primary visual organ in the eye. .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="F5FAFF"
| '''1619'''
| Scheiner is given credit to be the first person to correctly draw the diagram of the anatomy of the eye. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
|-bgcolor="CEDFF2"
| '''1672'''
| Marcello Malpighi described the embryonic development of the chicken. He drew many detailed diagrams of the chick eye. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1665'''
| Nicolaus Steno identified the choroid fissure in his study of a developing embryo of a chicken. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="CEDFF2"
| '''1754'''

| Albrecht von Haller studied the embryology of the eye. With help from his student Johann Gottfried Zinn, he contributed to the understanding of the development of the ciliary body, ciliary zonule, and their relationship with the lens and vitreous. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1817'''

| Christian Pander discovered the three embryonic germ layers, which he wrote about in his book. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/> Pander was the first to think of 'the optic vesicles as lateral evaginations' of the 'prosencephalon'; however, he was incorrect about the details regarding how 'the eye develops from these evaginations'. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="CEDFF2"
| '''1828-1837'''

| Karl Ernst von Baer studied embryology. He discovered that the optic vesicles were 'outgrowths of the embryonic forebrain' <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> which he believed was caused by pressure from fluids in the central nervous system. Von Baer also believed that the optic vesicle opens to form the pupil, and that fluid in the optic vesicle coagulates to form the vitreous body and lens. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1830'''

| Emil Huschke discovered that the lens forms from the invagination of the surface ectoderm. He concluded that the lens hence does not form ‘from the fluid of the optic vesicle’ <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> as previously thought.
|-bgcolor="CEDFF2"
| '''1832'''

| Emil Huschke wrote in his manuscript ‘Ueber die erste Entwinkenlung des Auges und die damit zusammenhängende Cyklopie’ that the lens capsule forms from the outer surface ectoderm, which detaches and moves back inward, which is later enclosed again by several membranes, such as by the cornea. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

Huschke also described how the optic cup and choroid fissure forms. He discovered that the optic vesicles are produced from the two-layered optic cup. However, he incorrectly described the destiny of the ‘individual optic cup layers’. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

|-bgcolor="F5FAFF"
| '''1838'''
| Matthias Jakob Schleiden and Theodor Schwann formulated the ‘cell theory’: “All living things are formed from cells, the cell is the smallest unit of life, and cells arise from pre-existing cells.” <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
|-bgcolor="CEDFF2"
| '''1839'''

| Theodor Schwann contributed a better understanding of the development of the lens through studying the foetus of a pig, which he wrote about in his book ‘Mikroskopische Untersuchungen Über Die Uebereinstimmung in Der Struktur Und Dem Wachsthum Der Thiere Und Pflanzen’. He wrote that the lens is made of ‘concentric layers’ of fibres which proceeds from an anterior to posterior direction. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1842'''
| Robert Remak gave the current names to the three embryonic germ layers: ectoderm, mesoderm and endoderm. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"
| '''1843'''
| Wilhelm Werneck published his book ‘Beiträge zur Gewebelehre des Kristallkörpers’. He wrote that the contents inside of the lens is not made of fluids, as was previously believed. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/> Werneck also discovered that the fibers of the lens continues to grow from the outside to the centre during embryogenesis. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

|-bgcolor="F5FAFF"
| '''1855'''

| Robert Remak wrote his book ‘Untersuchungen über die Entwickelung der Wirbelthiere’. He wrote about what he discovered in his studies of the development of the eye in the embryos of chickens, frogs, and rabbits. He wrote very descriptively about the embryology of lens formation, amongst other topics. He discovered that the ectoderm gives rise to the lens placode. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

|-bgcolor="CEDFF2"
| '''1858'''
| Henry Gray published his book 'Anatomy, Descriptive and Surgical'. He had also previously studied the embryonic development of the optic nerve and retina of chickens.
|-bgcolor="F5FAFF"
| '''1877'''
| Paul Leonhard Kessler wrote about the embryonic development of the lens in mice in his book ‘Zur Entwickelung des Auges der Wirbelthiere. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"
| '''1891'''
| Vincenzo Colucci studied newts and discovered their ability to regenerate the lens.<ref> Tsonis, P. A. (2001). Regeneration of the Vertebrate Lens and Other Eye Structures. eLS. (Online Publication). DOI: 10.1038/npg.els.0001102 </ref>
|-bgcolor="F5FAFF"
| '''1892'''
| Dr. Oscar Hertwig published his book ‘Text-Book of the Embryology of Man and Mammals. <ref> Hertwig, O. Text-book of the embryology of man and mammals. S. Sonnenschein 1901. (Translated from the 3d German ed. by Edward L. Mark.) </ref> It contains a very detailed description of the development of the eye, according to the findings at that time. [http://embryology.med.unsw.edu.au/embryology/index.php?title=Book_-_Text-Book_of_the_Embryology_of_Man_and_Mammals_16-2#The_Development_of_the_Eye]
|-bgcolor="CEDFF2"
| '''1895'''
| Gustav Wolff also independently studied newts and discovered their ability to regenerate the lens. .<ref> Tsonis, P. A. (2001). Regeneration of the Vertebrate Lens and Other Eye Structures. eLS. (Online Publication). DOI: 10.1038/npg.els.0001102 </ref>

|-bgcolor="F5FAFF"

| '''1900'''
| Carl Rabl published his book ‘Uber den Bau und die Entwicklung der Linse’. He wrote about the development of the lens in mammals, fish, birds, reptiles, and amphibians. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"
| '''1901'''
| Hans Spemann published his findings from his experimental studies about the formation of the lens in the frog. He found that the optic cup needed to be in contact with the ectoderm for normal development of the eye. <ref> Spemann, H. (1901). Über Correlationen in der Entwicklung des Auges. Verhand. Anat. Ges. 15: 61-79. </ref> <ref> Saha, M. (1991). Spemann seen through a lens. In Gilbert, S. F. (ed.). A Conceptual History of Modern Embryology. Plenum Press, NY. pp. 91-108.</ref>
|-bgcolor="F5FAFF"
| '''1906'''
| Brown ‘s book “The Embryology Anatomy and Histology of the Eye” was published. It contained detailed descriptions of the embryonic development of the eye according to the knowledge current at that time, mainly based on observations from embryos of rabbits and chickens. <ref> Brown, E.J. (1906). The Embryology Anatomy and Histology of the Eye. Chicago: Hazlitt & Walker. 1906 </ref>

|-bgcolor="CEDFF2"
| '''1907'''

| John Clement Heisler published his book ‘A Text-book of embryology’. It contains a chapter detailing the embryonic development of the eye, according to the knowledge current at that time. The book’s copyright has expired, so it can be viewed free online: [http://archive.org/details/atextbookembryo01heisgoog]

Julius Kollman also published his book 'Atlas of the Development of Man'. It contained very detailed description and illustrations showing the embryonic development of the human according to the knowledge current at that time. His illustrations were reused by many others after his time and built upon for further refined understanding of the embryology of the human.

Here are examples of Julius Kollman's excellent illustrations showing eye development in various stages:

'''Formation of Primary Optic Vesicle:'''
<gallery>
File:Kollmann691.jpg|The blue part at the bottom is the endoderm. The pink middle layer is the mesoderm. The top yellow layer is the ectoderm. The fold labelled as 'augenfeld' is the place where the optic vesicle will form.
File:Kollmann692.jpg|The eye area (augenfeld) is a bowl shaped bulge still located on the side walls.
File:Kollmann693.jpg| The neural tube is shown after removal of all of the ectoderm and ventral organs, such as heart, gut tube, etc. The primary optic vesicle forms a slightly flattened hollow protrusion on the forebrain.
File:Kollmann694.jpg|The lateral surface of the primary optic vesicle is slightly depressed, showing the first sign of the emergence of the secondary optic vesicle
</gallery>

'''Development of Lens:'''

<gallery>
File:Kollmann695.jpg|The bulging lateral wall of the primary optic vesicle is covered by a fairly well demarcated lens plate, a direct continuation of the ectoderm. Between the optic vesicle and the lens pit are some flattened spindle-shaped cells. In the adjoining mesoderm are cross-sections of capillaries.
File:Kollmann697.jpg|The lens still hangs together with the ectoderm. The primary eye vesicle is indented with respect to the lens. Between the lens and the lateral plate of the optic vesicle is a narrow space, which allows area to further develop later.
File:Kollmann698.jpg|4th Week of development. The internal organisation shows the secondary optic vesicle. A: The rear wall of lens is noticeable and is enveloped by mesoderm. B: The edges of the lens pit is already grown and the lens vesicles are formed, which is still related to the remaining ectoderm.
File:Kollmann699.jpg|The lens has now cut off from the ectoderm, but is still very superficial. Between it and the lateral lamina of the optic cup, there is a considerable space. The eye stalk has become longer and is enclosed together with the optic cup and lens of the mesoderm. The cornea, sclera and choroid make gradual development.
</gallery>

|-bgcolor="F5FAFF"

| '''1921'''
| Bailey and Miller published their textbook “Text-Book of Embryology “. <ref> Bailey, F.R. and Miller, A.M. (1921). Text-Book of Embryology. New York: William Wood and Co. (Note- This book is only at an early edited stage)</ref> It contains detailed description of the development of the embryonic eye according to the knowledge current at that time. [http://embryology.med.unsw.edu.au/embryology/index.php?title=Book_-_Text-Book_of_Embryology_18]

|-bgcolor="CEDFF2"
| '''1925'''

| Mann published his research article, in which he gives a detailed account of the development of the human iris. He divided the development of the iris into four stages: weeks 4-7 (before the ectodermal iris forms or before the anterior chamber forms); weeks 7-11 (anterior chamber appears, and mesodermal iris forms); weeks 11-12 (ectodermal iris forms); 3-8 months (muscles of the pupil forms from ectodermal iris, and the central portion of the mesodermal iris atrophies to make the pupil clear). <ref name="PMID18168466"><pubmed>18168466</pubmed></ref>
O Leser also published an article detailing the development of extraocular muscles in mammals he studied. <ref name="PMID18168498"><pubmed>18168498</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1939'''
| Holtfreter <ref> Holtfreter, J. (1939). Gewebeaffinitat, ein Mittel der embryonalen
Formbildung. Arch. Exp. Zellforsch. 23, 169-209. </ref> studied amphibians and observed that that the development of the eye stops at the ‘optic vesicle stage’ if there is no contact ‘with the epidermis and neural crest driven mesenchyme’. <ref name=”PMID11023863”><pubmed>11023863</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1955'''
| Barber published his book ‘Embryology of the human eye’. <ref> Barber AN: Embryology of the human eye. St. Louis. CV Mosby 1955</ref> In contains detailed descriptions of the embryological development of the human eye according to the knowledge current at that time. It contains many photographs of the eye at different stages of development.

|-bgcolor="F5FAFF"
| '''1957'''
| Coulombre studied a chicken embryo to find the role of intraocular pressure in the development of the chick’s eye, especially in regards to its control of the size of the eye structures. <ref name="PMID13469954"><pubmed>13469954</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1958'''
| Coulombre studied the development of the cornea and how it develops its transparency. <ref name="PMID13563560"><pubmed>13563560</pubmed></ref> He also studied the development of corneal curvature. <ref name="PMID 13519969"><pubmed> 13519969</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1962'''
| Coulombre studied the development of the conjunctival papillae and scleral ossicles. <ref name="PMID 14023393"><pubmed> 14023393</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1963'''
| Coulombre studied the development of lens fibers and their orientation. <ref name="PMID14077035"><pubmed>14077035</pubmed></ref> He also studied the development of pigmented epithelium. <ref name="PMID14023394"><pubmed>14023394</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1964'''

| Coulombre further studied the development of the lens to determine the role of the lens in eye growth. <ref name="PMID14189921"><pubmed>14189921</pubmed></ref> He also studied the role of thyroid in the development of the cornea and the development of corneal transparency. <ref name="PMID14211912"><pubmed>14211912</pubmed></ref> Mann also published his work called ‘The development of the human eye’, which contains detailed description of the embryonic development of the eye according to current knowledge at that time. <ref> Mann I. The development of the human eye. New York: Grune and Stratton 1964</ref>

|-bgcolor="CEDFF2"
| '''1965'''
| Coulombre published his findings regarding the regeneration of the neural retina from pigmented epithelium in the embryo of chickens. <ref name="PMID5833111"><pubmed>5833111</pubmed></ref> Smelser also published his findings on the embryological development and morphology of the lens. <ref name="PMID14340157"><pubmed>14340157</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1966'''

| Formation of the face and orbit occurs from the differentiation of neural crest cells. <ref name="PMID5969670"><pubmed>5969670</pubmed></ref> O’Rahilly also published findings of the development of the eye in the early stages of human embryos. <ref> O'Rahilly, R. 1966 The early development of the eye in staged human embryos. Contr. Embry. Carnegie Inst., Wash., 38: 1–42</ref>

|-bgcolor="CEDFF2"
| '''1968'''
| Findings of the postnatal development of the retina of rats was published. <ref name="PMID5640327"><pubmed>5640327</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1969'''

| Mann again published his work called ‘The development of the human eye’. He stated that that the lens in humans forms completely from the ectoderm. <ref name=”Mann I. The Development of the Human Eye. New York, USA: Grune & Stratton, Inc; 1969”> Mann I. The Development of the Human Eye. New York, USA: Grune & Stratton, Inc; 1969</ref> Coulombre also studied the development of the lens, and took note of its size, shape and orientation throughout its developmental stages. <ref name="PMID 5772716"><pubmed> 5772716</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1970'''
| Coulombre again further studied the regeneration of the neural retina from pigmented epithelium of embryos of chickens. <ref name="PMID 5472476"><pubmed> 5472476</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1971'''

| Coulombre further studied the development of the lens. This time he focused on analysing the histological mechanisms in the reconstitution of the lens from implanted lens epithelium. <ref name="PMID 4925671"><pubmed> 4925671</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1973'''
| A research article was published, detailing the embryonic development of the retina of humans. <ref name="PMID 6650859"><pubmed> 6650859</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1976'''

| Geeraets published his observations of the closure of the embryonic optic fissure in golden hamsters, using the electron microscope. <ref name="PMID 1266776"><pubmed> 1266776</pubmed></ref> Kornneef also published an article based on his studies of the development of connective tissue in the human orbit. <ref name="PMID 1020699"><pubmed> 1020699</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1981'''
| A research article was published detailing how myelin forms in the optic nerve of humans. <ref name="PMID 7224936"><pubmed> 7224936</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1983'''
| O’Rahilly’s further research developments was published, reporting the timing and sequence of events in the development of the embryonic human eye. <ref name="PMID 6650859"><pubmed> 6650859</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1990'''

| Van Driell et al. <ref>Driell, D. Van; Provis, J.M.; Billson, F.A.: Early differentiation of ganglion, amacrine, bipolar and Muller cells in the developing fovea of the human retina. J. Comp. Neurol. 291: 203-219.</ref> studied the manner in which amacrine, bipolar, retinal ganglion cells, and Muller cells differentiate in the developing fovea of the retina of a 15-week old human foetus. <ref name="PMID1628748"><pubmed>1628748</pubmed></ref> Tripathy also published an article providing evidence that the lacrimal glands in humans originates from the neuroectoderm. <ref name="PMID2406219"><pubmed>2406219</pubmed></ref>

|}

==Development, Structure and Function of Ocular Components==

The eye itself is formed from several components; notably the optic placode of the head ectoderm, the optic vesicle from the neural tube, and mesenchyme from the mesoderm and neural crest cells. The optic placode contributes the lens to the eye, the optic vesicle gives rise to layers of the retina, while the mesenchyme will produce the ciliary body, iris, choroid and sclera.<ref>http://www.vetmed.vt.edu/education/curriculum/vm8054/eye/EMBYEYE.HTM</ref> Cells from the neural tube will also produce the optic nerve, which receives nerve impulses from the retina of the eye. Eyes initially form as laterally paired structures and migrate medially in the human embryo. In other animals such as birds and lizards, the eyes do not migrate and develop laterally on the head. The optic placodes become prominent on the surface of the embryo at approximately Stage 14 of development.

[[File:Stage14 sem2b-limb.jpg|200px|thumb|left|A Stage 14 embryo showing the location of an otic placode.<ref name="http://embryology.med.unsw.edu.au/embryology/index.php?title=ANAT2341_Lab_6_-_Early_Embryo">http://embryology.med.unsw.edu.au/embryology/index.php?title=ANAT2341_Lab_6_-_Early_Embryo</ref>]] [[File:Stage 13 image 060.jpg|400px|thumb|center|A cross section showing the organisation of the developing brain, the optic vesicle and the lens (optic) placode.<ref name="http://embryology.med.unsw.edu.au/embryology/index.php?title=ANAT2341_Lab_6_-_Early_Embryo"/>]]

===Optic Nerve===

The optic nerve consists of nerve fibres that transmit information from the retinal photoreceptor cells to the brain. The optic nerve is formed from the optic stalk, which develops as the optic vesicle migrates from its origin in the neural tube to its destination - the surface ectoderm - where it will fuse with the optic placode (also known as the lens placode, which will contribute the lens to the eye).<ref name="PMID11687490"><pubmed>11687490</pubmed></ref>

[[File:Formation of the optic vesicle 1.jpg|400px|thumb|left|Fig. 1: Early formation of the optic vesicle from the neural groove.]] [[File:Formation of the optic vesicle 2.jpg|400px|thumb|center|Fig. 2: The optic vesicle at a later stage, showing the optic stalk.]]

As can be seen in Figure 1 above, the optic vesicle forms from the neural tube. However, note that the neural tube has not yet closed, and is still the neural groove at this point. Figure 2 then shows the optic vesicle at slightly later stage in the same simplified cross-section of the embryo, as it migrates from the neural tube to the surface ectoderm. Note the presence of the optic stalk which links the optic vesicle to the neural tube. Later in development, this primitive structure will become the optic nerve, which will link the eye to the brain.

The nerve fibres themselves will initially originate from the retinal ganglion cells in the eye during week 6.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008">Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008</ref> After two weeks, these fibers will have grown along the inner wall of the optic stalk and have reached the brain. They grow both in length and width, with the nerve fibres filling the hollow optic stalk to form the solid optic nerve. More than one million nerve fibers will eventually make up the optic nerve, along with glial cells which arise from the inner wall of the optic stalk itself.<ref><pubmed>1451666</pubmed></ref> Myelinisation of the optic nerve begins much later in development at around 7 months, beginning at the optic chiasm and moving towards the eye.<ref><pubmed>7224936</pubmed></ref> The optic chiasm forms just before the nerves reach the brain, and is where half the nerve fibres from each eye will cross over to the opposite side of the brain. This is demonstrated in Figure 3. Note the crossing over of the optic nerves just before they enter the brain, at the optic chiasm. This organisation is now much more familiar, with the eyes near the ectoderm and the optic nerve leading through the mesoderm to the brain buried deep in the embryo.

[[File:Formation of the optic nerve and chiasm 1.jpg|400px|thumb|center|Fig. 3: A recognisable brain and eye structure in later development.]]

===Retina===

The retinal component of the eye is formed when the optic vesicle folds in upon itself, forming the optic cup (see Figure 4). In doing so it creates two layers - an inner wall and an outer wall of the optic cup (Figure 5). These two layers of the optic cup will give rise to the two layers of the retina - the inner neural retina, and the outer pigmented epithelium.<ref name="PMID11687490"/> Note the existence of the space between the two layers of the retina. This is known as the intraretinal space and disappears by the 7th week of development, however the two layers never completely fuse and can become separated as a result of physical trauma to the head - leading to a detached retina and loss of vision.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/>

The inner wall of the optic cup, which will give rise to the neural retina, consists of a layer of pseudostratified cells (see Figure 6) that later differentiate into rod, cone, bipolar, ganglion, horizontal, amacrine and glial cells of the retina (Figure 7).<ref name="PMID18168748"><pubmed>18168748</pubmed></ref> The outer wall of the optic cup consists of a layer of cuboidal cells that contain melanin - the light absorbing pigment. The function of this layer is to absorb light and prevent internal reflection of light within the eye, which would impair our ability to form distinct images. Interestingly, in some animals such as cats, this layer actually reflects light intentionally to increase the amount of light available to the eye in low-light conditions. This is why cats seem to have eyes that glow in the dark.<ref>http://dialspace.dial.pipex.com/agarman/bco/fact4.htm</ref>

[[File:Formation of the optic cup 1.jpg|400px|thumb|left|Fig. 4: Mechanism of optic cup formation.]] [[File:Formation of the optic cup 2.jpg|400px|thumb|center|Fig. 5: Layers of the optic cup in retina development.]]

The inner wall itself is divided into two components - the inner neuroblastic layer and the outer neuroblastic layer (see Figure 6). The outer neuroblastic layer forms the rod and cone cells while the inner neuroblastic layer forms the remaining cell types found in the retina - the bipolar, ganglion, horizontal, amacrine and glial cells (Figure 7).<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/> The organisation of the retina is interesting in that incoming light passes through several layers of these neural retina cells before it is detected by rod and cone cells at the back of the retina, and then nerve signals are passed back through the layers of neural retina cells that the light just passed through moments before - a seemingly strange design that the eye does not share with man-made light-capturing devices such as a camera (imagine putting the wires in front of the image sensor!).

Differentiation of the neuroblastic layers into neural retina cells occurs in a pattern both within the layers and across the retina. Cells differentiate from the inner neuroblastic layer to the outer neuroblastic layer, and differentiate from the central retina to the peripheral retina.<ref name="PMID18168748"/> The macula is first identifiable in week 22 when ganglion cells start to form multiple rows, and the primitive fovea begins to form at approximately the same time as a depression in the macula.<ref><pubmed>6462623</pubmed></ref> It is not until 15-45 months after birth that this area becomes exclusively populated by cone cells and becomes the fovea centralis - the area of the retina with the highest visual acuity.

[[File:Formation of the retina 1.jpg|400px|thumb|left|Fig. 6: Cross-section of the primitive retina showing cell types and layers.]] [[File:Formation of the retina 2.jpg|400px|thumb|center|Fig. 7:Cross-section of a developed retina showing cell types and layers.]]

===Ciliary Body===

The ciliary body consists of ciliary processes and three portions of fibres that constitute the ciliary muscles. It functions to maintain normal eye physiology as well as playing a direct role in accommodation.

During development, the ciliary processes form slightly posterior to the iris, developing from part of the anterior rim of the optic cup. It is thought that the folded structure of the ciliary processes is brought about by intraocular pressure and specific signalling pathways.<ref name="PMID16959249"><pubmed>16959249</pubmed></ref> While the ciliary muscles and the endothelial cells of the ciliary blood vessels are chiefly formed by mesenchymal cells<ref><pubmed>16249499</pubmed></ref>, the neural crest and neuroectoderm also contribute to their development.<ref><pubmed>12127103</pubmed></ref> The normal development of the ciliary body is dependent on the correct expression of bone morphogenetic protein (BMP)-4, which is a member of the transforming growth factor-β superfamily.<ref><pubmed>1222340</pubmed></ref> Napier and Kidson (2007) summarised numerous genes that have been associated with ciliary body development, however their direct roles have not been well documented.<ref name="PMID16959249"/>

===Iris===

The iris is a thin layer that develops at the end of the third month of development and is derived from the anterior rim of the optic cup. The stroma of the iris develops from cells of neural crest cell origin.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/> The muscles that are responsible for the dilation and constriction of the pupil (dilator pupillae and sphincter pupillae muscles) form from the neuroectoderm of the optic cup. These cells are initially epithelial cells that then transform into smooth muscle cells. <ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"></ref>. The invagination of the optic vesicle which creates the optic cup, also causes the formation of the optic cup lip. This is the region of the where the epithelium doubles back, separating the outer pigmented layer and the inner nonpigmented layer. This is the edge of the iris that borders on the pupil<ref><pubmed> Retinal and anterior eye compartments derive from a common progenitor pool in the avian optic cup</pubmed></ref>.

The final colour of the iris is not evident until the postnatal period. It is determined by a number of genes including IRF4, SLC24A4 and MATP<ref><pubmed>19710684</pubmed></ref>. Other features such as crypt frequency, furrow contractions, presence of peripupillary pigmented ring, and number of nevi also become evident during development<ref><pubmed>21835309</pubmed></ref>. Mutations in Pax6 have been shown to cause partial or complete loss of the iris <ref><pubmed>12386935</pubmed></ref>.

===Cornea===

The cornea is the transparent, avascular, most anterior portion of the eye. It is responsible for conducting light into the eye and focusing it on to the retina, as well as maintaining the rigidity of the eyeball. It consists of 5 layers- the epithelium, Bowman’s layer, stroma, Descemet’s membrane and the endothelium.

The epithelium and endothelium of the cornea first appear during the 5th week of gestation. The epithelium of the external surface of the cornea is derived from surface ectoderm, while the mesenchyme is derived from the mesoderm<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"/>. The endothelium is a two-cell cuboidal layer which is made up of differentiated neural crest cells that were initially from the optic cup. By week 8 the endothelial cells begin to secrete a basement membrance which later forms Descemet’s membrane<ref><pubmed>6511224</pubmed></ref>. At approximately 16 weeks gestation the Bowman’s membrane begins to form from the thickening of the stroma that is located under the corneal epithelium<ref>Riordan-Eva P, Whitcher JP. Vaughn and Asbury's General Ophthalmology, Lange Medical Books/McGraw Hill. 2004:25–27</ref>. During the third month glycosaminoglycans secreted by fibroblasts form the ground substance of the cornea, with collagen fibrils and keratan sulphate also appearing around this time. Shortly after this tight junctions form between the endothelial cells<ref><pubmed>19481138</pubmed></ref>. Fibroblast growth factor causes the epithelial cells to proliferate<ref><pubmed>20105280</pubmed></ref>.

Towards the end of the gestational period the cornea becomes larger due to the production of aqueous humor<ref>Yanoff M, Duker JS. Ophthalmology. Mosby; St. Louis, MO: 2004</ref>. The final transparent structure develops because hyaluronidase removes hyaluronic acid, thyroxine causes dehydration of the stroma, and the entire structure becomes avascular<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/>. Numerous genes have been implicated in the development of the cornea, these include, but are not limited to, PAX6, PITX2, FOXC1, MAF, TMEM114, SOX2, OTX2 and BMP4<ref><pubmed>18637741</pubmed></ref>. Pax6 and Pax6(5a) isoforms are essential for the normal development of the eye. Over or under expression can both lead to major structural abnormalities<ref><pubmed>18386822</pubmed></ref>.

===Lens===

The lens has its origin from the optic placode, which develops on the ectodermic surface of the embryo and migrates both medially and inwards into the embryo. The lens allows accommodation of the eye, and adjusts its thickness in order to focus on near or far objects. The study of lens development was one of the first to highlight the importance of inductive signaling in development, with Spemann's pioneering work at the start of the 20th century, finding that the absence of retinal development resulted in the absence of lens formation.<ref name="PMID11687490"/> Indeed, it has been consistently shown that the interaction of the migrating optic vesicle with the surface ectoderm of the head is vital in producing differentiation of the lens.<ref name="PMID15558475"><pubmed>15558475</pubmed></ref> The mechanism of interaction is complex but basically involves upstream genes switching on downstream genes, with the genes eventually producing specialised proteins which constitute the lens. The whole process starts with the signaling molecules from the optic cup initiating a thickening of the surface ectoderm of the head (Figure 8). It is thought that this region of specific ectoderm is responsive to the signaling molecules, as lens formation is incomplete or absent when ectoderm from the lateral portion of the embryo (i.e. non-head ectoderm) is exposed to the same inductive signaling processes.<ref name="PMID9216064"><pubmed>9216064</pubmed></ref> Pax6 has been shown to be one of the major genes required for differentiation of the lens, which in turn switches on transcriptional genes such as Sox 1, 2 and 3 among others - producing water-soluble proteins called crystallins - responsible for giving the lens its transparency and refractive properties.<ref name="PMID9609835"><pubmed>9609835</pubmed></ref>

[[File:Formation of the lens 1.jpg|400px|thumb|left|Fig. 8: The importance of the optic cup in lens differentiation.]] [[File:Formation of the lens 2.jpg|400px|thumb|center|Fig. 9: The lens placode separates from the ectoderm and migrates into the mesoderm forming the lens vesicle.]]

The lens placode invaginates from the head ectoderm and migrates into the mesoderm (Figure 9). Once this structure (now known as the lens vesicle) is in place opposite the optic cup, the combined structure is referred to as the optic globe and resembles a recognisable eye structure. The lens continues to differentiate further, as mentioned above, through the formation of crystallin proteins, which give the lens its unique properties and allows for the fine control over the degree of refraction that takes place.

===Aqueous Chambers===

There are both anterior and posterior aqueous chambers of the eye which contain aqueous humour. A space develops in the mesenchyme situated between the lens and cornea to form the anterior aqueous chamber. The mesenchyme located superficially to this chamber forms the mesothelium as well as the transparent portion of the cornea.

The posterior chamber develops from a similar space in the mesenchyme, however it is located between the iris and the lens. The anterior and posterior chambers are able to communicate with one another once the papillary membrane vanishes and the pupil is formed. This channel is known as the scleral venous sinus.<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011">Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011</ref>

Contained within the aqueous chambers is aqueous humor. The production of aqueous humor is dependant on the development of the ciliary body. It is produced in the ciliary processes and it’s production is a metabolic process driven by the delivery of oxygen and the removal of wastes via the ciliary circulation<ref><pubmed>20801226</pubmed></ref>.

===Choroid and Sclera===

The choroid and sclera are adjacent layers that surround the eye and act to vascularise and protect the eye respectively. They are formed from neural crest and mesoderm-derived mesenchyme which condenses around the optic cup and lens vesicle between weeks 5 and 7 of development to form a primitive eyeball structure known as the optic globe.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/> Blood vessels first start to appear in the choroid layer at approximately week 15, and arteries and veins can be distinguished by week 23.<ref>Development of the Choroid and Related Structures, K. Sellheyer, Eye (1990) 4, 255-261</ref> Inductive processes are thought to play a vital role during formation of the choroid and sclera; with the retinal pigmented epithelium inducing differentiation of the surrounding mesenchyme while at the same time the neural crest-derived mesenchyme contributing components to the retinal pigmented epithelium such as melanocytes.<ref name="PMID1628748"/> In addition to having functional roles themselves, the primitive choroid and sclera also contribute components to the developing ciliary body and cornea (Figure 10). In the adult eye, the choroid is continuous with the ciliary body and the sclera with the cornea.

[[File:Formation of the choroid and sclera 1.jpg|400px|thumb|center|Fig. 10: The choroid and sclera derives from mesenchyme surrounding the optic cup.]]

===Eyelids===

The eyelids are ectodermal and mesodermal in origin and are an extension of the skin which covers and protects the eye. The surface ectoderm gives rise to the conjunctiva, skin epithelium, hair follicles, cilia, Zeis glands, glands of Moll, and meibomian glands. <ref name=" Cook CS, Ozanics V, Jakobiec FA. (1994) Prenatal development of the eye and its adnexa. In Tasman W, Jaeger EA, editors: Duane’s foundations of clinical ophthalmology, vol 1, Philadelphia, 1994, Lippincott. "> Cook CS, Ozanics V, Jakobiec FA. (1994) Prenatal development of the eye and its adnexa. In Tasman W, Jaeger EA, editors: Duane’s foundations of clinical ophthalmology, vol 1, Philadelphia, 1994, Lippincott. </ref> The mesenchyme gives rise to the tarsal plates, levator muscles, orbicularis muscles, and tarsal muscle of Muller. <ref name=" Cook CS, Ozanics V, Jakobiec FA. (1994) Prenatal development of the eye and its adnexa. In Tasman W, Jaeger EA, editors: Duane’s foundations of clinical ophthalmology, vol 1, Philadelphia, 1994, Lippincott. "/> Eyelid formation can be first noted during week 5 when small grooves develop in the surface ectoderm (Figure 11).<ref><pubmed>7364662</pubmed></ref> These small grooves deepen and extend into the mesoderm and the primitive eyelid structures grow towards one another, eventually fusing together during week 8.<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"/> It is not until week 26-28 that the eyelids will separate again. The anterior surface of the eyelid becomes covered by two layers of epithelium; this forms the epidermis of the eyelids. <ref name="Kikkawa DO, Lucarelli MJ, Shovlin JP, et al: Ophthalmic facial anatomy and physiology. In Kaufman PL, Alm A, editors: Adler’s physiology of the eye, St Louis, 2003, Mosby, pp 16."> Kikkawa DO, Lucarelli MJ, Shovlin JP, et al: Ophthalmic facial anatomy and physiology. In Kaufman PL, Alm A, editors: Adler’s physiology of the eye, St Louis, 2003, Mosby, pp 16.</ref> Tarsal plates then begin to develop, which eventually leads to the formation of meibomian glands. <ref name="PMID1628748"/> The ectoderm reflects over the developing cornea to form the conjunctival sac, a space that is filled by secretions from the lacrimal gland in order to allow smooth motions of the eyelid over the eye and also to clean the cornea and prevent accumulation of particles on the eye that may disrupt vision. By the time the eyelids separate, the eye has all its major components present (Figure 12), and further development consists mainly of growth and vascularisation.

[[File:Formation of the eyelid 1.jpg|400px|thumb|left|Fig.11: Small grooves in the ectoderm of the head - the precursors to an eyelid.]] [[File:Formation of the eyelid 2.jpg|400px|thumb|center|Fig. 12: The eye after week 8 of development. Note however, that the eyelids remain fused until weeks 26-28.]]

===Lacrimal Glands===

There are three stages of lacrimal gland development. The first is the presumptive glandular stage in which the superior conjunctival fornix epithelium thickens and the surrounding mesenchymal cells condense. These mesenchymal cells are of neural crest origin<ref><pubmed>9882499</pubmed></ref>. The second stage sees the development of nodular formations around the superior conjunctival fornix and the formation of lumina within the epithelial buds, this stage is therefore known as the bud stage. Innervation and vascularisation also occur during this stage. The final morphological changes occur during the glandular maturity stage which occurs in weeks 9-16 when the lacrimal glands begin to resemble the mature glands. During the 13th week the lacrimal and zygomatic nerves anastomose<ref><pubmed>14635806</pubmed></ref>.

These glands are responsible for the production of tears however they do not start to function until 1-3 months after birth. The mature lacrimal gland is made up of two lobes- the palpebral and orbital lobes.

==Current Research==

Not only are there still many important processes and components of eye development that we would like to understand, this knowledge also contributes to the development of treatments for eye disorders and technologies such as the bionic eye.

===The impact of visible light on the immature retina===

<pubmed>22405869</pubmed>

The authors mentioned in this article <ref name="PMID22405869"><pubmed>22405869</pubmed></ref> that they were interested in investigating the effect of light on postnatal eye development in mice, because mice are born with fused eyelids, which separate 12 days after birth. Before the eyelids separate, the retina develops in mice with very little radiation from light. It is believed that the darkness plays a role in the development of the retina in mice, which is why their eyelids are fused for 12 days after birth. Therefore the authors were interested to see what effect light would have on postnatal retinal development of mice, with special interest in retinal ganglion cells (RGC). In their experiment, they surgically opened the eyelids on the right eyes of some of the mice to expose them to visible light 12 hours per day, while they left some other mice in the dark after surgical separation of their eyelids. They also kept the left eyes of the mice naturally fused as controls in the experiment. Their results showed that early light exposure in mice causes a decrease in retinal ganglion cells because it affects cellular apoptosis in the retina. The authors also observed that early exposure to light in mice causes lumican mRna transcription to resume and to quickly increase. (Lumican normally stays silent in retina after birth).

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===GABA Maintains the Proliferation of Progenitors and Non-Pigmented Ciliary Epithelium===

<pubmed>22590629</pubmed>

{| width=800px
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| GABA is an ‘inhibitory neurotransmitter’ in the central nervous system of adults. <ref name="PMID22590629"><pubmed>22590629</pubmed></ref> It is responsible for controlling proliferation of stem cells and progenitor cells. The authors of this article <ref name="PMID22590629"/> was interested to find the effects of GABA on proliferation of progenitor cells and non-pigmented ciliary epithelial cells (NPE) in the retina. Their study focused on progenitor cells and non-pigmented epithelium of the ciliary body in chickens. Non-pigmented epithelial cells in chickens arise from the neuroepithelium of the optic cup. They share similar functions as progenitors of the early retina, such as expression of Chx10 and Pax6 genes. It is not agreed upon whether epithelial cells of the ciliary body have stem cell properties. However, it has been found that these cells can be cultured and transplanted into retinas that are injured, in order to replace neurons that were previously lost. However, there is not much known about what factors regulate the proliferation of stem cells. Hence the authors were interested in finding the effects of GABA on proliferation of retinal cells. Their results showed that non-pigmented epithelial cells in chickens ‘express extrasynaptic-like GABAA receptors’ that have the ability to regulate cell proliferation. It has been found that inhibiting these ‘GABAA receptors’ also causes a decrease in proliferation of retinal progenitor cells and non-pigmented epithelial cells in 'the intact E8 retina’. <ref name="PMID22590629"/>

|
[[File:Gaba-effects-retina.JPG|thumbnail|250px|'''GABAA receptor mediated effects on retinal progenitor cell proliferation'''
]]
|}

-------------------------

===Stem Cells===

[http://www.advancedcell.com/patients/clinical-trial-information/ Advanced Cell Technology] is a biotechnology company which is currently running two clinical trials that utilise human embryonic stem cell derived retinal pigmented epithelial cells. These trials are examining the possibility of using these cells to treat stargardt's macular dystrophy and dry age-related macular degeneration.

Despite the discovery of human embryonic stem cells (hESCs) 13 years ago, these trials are the first to describe the subretinal transplantation of hESCs into humans. The participants in these trials were sufferers of Stargardt's macular dystrophy or dry age-related macular degeneration, which is the chief cause of blindness in the developed world.

The trials were relatively successful in the sense that the hESC-derived retinal pigment epithelium cells that were implanted integrated well into the existing tissue, and there were no signs of hyperproliferation, abnormal growth, or rejection. The authors hope that in future this technique will be applied to patients in the earlier stages of disease, preventing disease progression<ref><pubmed>22281388</pubmed></ref>.

-------------------

[[File:Bionic_eye.JPG|right|thumb|300px|Early prototype of the bionic eye.]]
===Bionic Eye===

[http://bionicvision.org.au/ Bionic Vision Australia] are the first organisation to implant a bionic eye. In 2012 a prototype made up of a retinal implant with 24 electrodes was implanted into 3 different patients with retinitis pigmentosa.

A camera is used to capture images which are transferred to an external data processing unit. From here the data is processed and transmitted via a wire to the implanted receiver, which in turn sends the signal to the retinal implant. The retinal implant is then able to stimulate the visual pathways in the brain.

Bionic Vision Australia hopes that in 2013, trials for a wide-view device that consists of 98 electrodes will be in progress. This prototype will be inserted into the suprachoroidal space in order to prevent mechanical damage to the retina. Trials for a more advanced high-acuity device with 1024 electrodes are planned for 2014. The electrode array contained in this device will be made of diamond to prevent irritation of surrounding tissues. These devices are expected to be suitable for patients with retinitis pigmentosa and age-related macular degeneration. The eventual goal will be to provide a completely wireless device which gives the patient high visual acuity.

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===MIP/Aquaporin 0 Represents a Direct Transcriptional Target of PITX3 in the Developing Lens===

<pubmed>21698120</pubmed>

{| width=800px
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|PITX3 plays a siginificant role in the development of lens in vertebrates. If there is a deficiency is PITX3, it causes a range of problems in humans such as microphthalmia, Peter’s anomaly, or isolated cataracts. Mutation of PITX3 also causes degeneration of the lens in zebrafish and mice. It is therefore important to understand what factors may affect the decrease in PITX3, as a normal level of PITX3 is needed to maintain normal eye development. The authors wanted to investigate specific genes which are affected by PITX3. Previous research has shown that MIP and Aquaporin causes defects in the lens in both mice and humans. MIP and Aquaporin are targeted by PITX3, so their imbalance is interrelated in the cause of defects in the lens. Therefore it has been previously proven that PITX3 is needed for normal development of the lens. However, there has not been much information previously known regarding the exact effect that PITX3 has, or the specific genes it targets. Since MIP and Aquaporin is common genes found in humans, mice and zebrafish, the authors <ref name="PMID21698120"><pubmed>21698120</pubmed></ref> chose to study these genes to understand the pathway that PITX3 takes and its exact involvement in the development of the lens. Their results proved that deficiency in MIP and Aquaporin indeed affects normal development of the lens, and it is indeed related to deficiency in PITX3. However, there is still more research needed to understand PITX3 and the genes it interacts with, and their effect in ocular development.

|
[[File:Mip1-expression-in-pitx3.jpg|thumbnail|250px|'''Analysis of mip1 expression in pitx3-mo and control embryos via in situ hybridization and RT-PCR''']]
|}

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===Activation of c-Jun N-terminal kinase (JNK) during mitosis in retinal progenitor cells.===

<pubmed>22496813</pubmed>

{| width=800px
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| In the past, most studies about c-Jun N-terminal kinase (JNK) in the retina have been in relation to neurodegeneration. <ref name="PMID22496813"><pubmed>22496813</pubmed></ref> Therefore the authors in this article were interested in investigating the function of c-Jun N-terminal kinase in the retinal progenitor cells in neonatal rats. <ref name="PMID22496813"/> In the experiment, they took retinal tissue from newborn rats and fixed them, and subsequently examined them using confocal microscopy and fluorescence to discover c-Jun N-terminal kinase ‘phosphorylation by immunohistochemistry’. <ref name="PMID22496813"/> Mitotic cells in the retina were identified during the experiment. The results of their experiment revealed that c-Jun N-terminal kinase is phosphorylated in the developing retina of neonatal rats during the mitosis of progenitor cells. <ref name="PMID22496813"/> This shows that c-Jun N-terminal kinase can control the proliferation of progenitor cells in the developing retina. Their experiment also revealed that inhibiting c-Jun N-terminal kinase causes disruptions to the mitotic cell cycle by reducing the cell numbers in anaphase. <ref name="PMID22496813"/> However, inhibiting c-Jun N-terminal kinase did not change the cell numbers in metaphase or prophase. <ref name="PMID22496813"/>

|
[[File:JNK1.png|thumbnail|300px|'''"JNK is phosphorylated during mitosis of retinal progenitor cells."''']]
|}

----------------------------

===LRP5 is required for vascular development in deeper layers of the retina===

<pubmed>20652025</pubmed>

{| width=800px
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|
The lipoprotein receptor-related protein 5 (LRP5) has a significant function in the development of retinal vasculature.<ref name="PMID20652025"><pubmed>20652025</pubmed></ref> Research has shown that mutations of the LRP5 causes loss of function, due to incomplete development of retinal vessel network, in both humans and mice. The authors investigated how mutations occur in the LRP5, which leads to abnormal development of the retinal vasculature. They have studied retinal endothelial cells in mutant mice in their study. Their results showed that in retina with mutated LRP5, endothelial cells in the retinal vasculature primarily produced cell clusters in the inner-plexiform layer instead of migrating into deeper layers of the retina to form normal retinal vasculature. The authors also discovered that there was a decrease in Slc38a5, which is “a Müller cell-specific glutamine transporter”, in mice with mutated LRP5. Their results lead the authors to conclude that normal LRP5 is very important in the development of normal retinal vasculature due to their role in causing migration of retinal endothelial cells in the deeper layers of the retina. LRP5 is also important for retinal interneurons and Müller cells to function correctly.

|
[[File:Retina-cell-clusters.JPG|350px|thumbnail|'''Endothelial cells form thick clusters in the LRP5 mutant retina''']]
|}

-----------------

===Astrocyte-Derived Vascular Endothelial Growth Factor===

<pubmed>20686684</pubmed>

{| width=800px
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|
Vascular endothelial growth factor (VEGF) has an important role in normal development of retinal vasculature. <ref name="PMID20686684"><pubmed>20686684</pubmed></ref> In the process of vascularisation of the retina, the retinal astrocytes (both vascularised and not yet vascularised) expresses the vascular endothelial growth factor. <ref name="PMID20686684"/> This fact indicates that vascular endothelial growth factor that are derived from astrocytes of the retina plays an important role in vessel maturation and angiogenesis. <ref name="PMID20686684"/> Therefore the authors wanted to test the role of vascular endothelial growth factor that are derived from astrocytes to find further confirmation. ‘Cre-lox technology’ was used in the experiment to remove the vascular endothelial growth factor from mice retinal astrocytes in the developmental period. <ref name="PMID20686684"/> The results showed that removing vascular endothelial growth factor that are derived from astrocytes caused ‘the regression of smooth muscle cell-coated radial arteries and veins’ from the effects of hyperoxia. <ref name="PMID20686684"/> Hence, this result indicates that vascular endothelial growth factor plays an important role in stabilising blood vessels during the development of the retinal vasculature. <ref name="PMID20686684"/> It has been suggested that this finding may be of relevance to retinopathy in premature neonatal humans. <ref name="PMID20686684"/>

[[File:Astrocyte-vegf-deletion.JPG|250px|thumbnail|'''"Astrocyte specific deletion of VEGF." ''']]
|
[[File:Effect-of-vegf-on-retinal-vasculature.JPG|250px|thumbnail|'''"Effects of astrocyte-derived VEGF on retinal vascular development."''']]
[[File:Vegf-protects-vessels.JPG|250px|thumbnail|'''Astrocyte-derived VEGF protects vessels from hyperoxia. ''']]

|}

==Useful Links==

{{External Links}}

[http://www.youtube.com/watch?v=Xme8PA6xv-M Visualisation of eye development in the embryo]

[http://www.youtube.com/watch?v=wJE6pYwAMVU Brief Video on Embryonic development of the eyes]

[http://www.embryo.chronolab.com/sense.htm Embryonic Development of the eye]

[http://webvision.med.utah.edu/book/ Webvision free online textbook]

[http://www.ophthobook.com/chapters/ Free basic online book about the eyes]

[http://www.youtube.com/watch?v=deEjbVdnwyA&feature=related Anatomy of the Eyes- Video]

[http://www.vetmed.vt.edu/education/curriculum/vm8054/eye/EMBYEYE.HTM Simple eye embryology explanation]

[http://www.vetmed.vt.edu/education/curriculum/vm8054/eye/chambers.htm The chambers of the Eye]

[http://www.sciencedirect.com/science/journal/13509462 Progress in retinal and eye research journal]

[http://www.sumanasinc.com/webcontent/animations/content/visualpathways.html Animation showing the visual pathway]

[http://www.youtube.com/watch?v=f0JpsTgy6ck Video describing the layers of the retina]

[http://www.youtube.com/watch?v=Wm66gCid-kE&NR=1&feature=endscreen Video on visual processing in the retina]

[http://www.ncbi.nlm.nih.gov/books/NBK10024/ Development of the vertebrate eye]

[http://www.childrensvision.com/development.htm Easy-to-understand descriptions of the development of vision after birth]

[http://archive.org/details/atextbookembryo01heisgoog John Clement Heisler's historic textbook on Embryology (1907) ]

==Glossary==

'''Accommodation''' - changing the focal length of the lens in order to focus on an object.

'''Amacrine cells''' - interneurons located in the retina

'''Anterior chamber''' - Fluid-filled area located between the iris and cornea.

'''Choroid''' - The middle coat of the eye, located between the sclera and retina, which contains blood vessels that nourish the structures in the eye.

'''Ciliary body''' - Structure located behind the iris which secretes aqueous humour. It contains ciliary muscle, which is involved with changing the shape of the lens for accommodation.

'''Cornea'''- a transparent section in the anterior of the eye which acts as a window over the pupils, and is involved with refracting light as it enters the eye.

'''Downstream genes''' - genes that are activated by other "upstream genes".

'''Ectoderm''' - outermost layer of germ cells in an early embryo.

'''Endoderm''' - innermost layer of germ cells in an early embryo.

'''Extraocular muscles''' - Muscles that control the movement of the eyeball.

'''Glial cells''' - non-neuronal cells that provide structure and protection to neurons as well as producing myelin.

'''Inductive signaling''' - a process whereby the secretion of factors from one cell or tissue triggers a response in another.

'''Iris'''- A circular shaped muscle which controls the opening and contraction of the pupil.

'''Lens'''- A structure inside the eye which refracts light as it enters the eye for clear vision.

'''Lens vesicle''' - the cavity of invaginated ectoderm from the optic placode that will form the lens.

'''Macula''' - a highly pigmented, oval-shaped area located near the centre of the retina. Important for visual acuity.

'''Mesenchyme''' - undifferentiated, loose connective tissue.

'''Mesoderm''' - middle layer of germ cells in an early embryo.

'''Mesothelium''' - the epithelial layer of the mesoderm.

'''Myelinisation''' - development of a myelin sheath around a nerve fibre.

'''Neural crest''' - a portion of the ectoderm situated next to the neural tube.

'''Neural groove''' - a large invagination on the dorsal surface of the embryo which will close off and form the neural tube.

'''Neural tube''' - hollow structure that results from the folding of the neural plate and eventually forms the central nervous system.

'''Neuroblastic layer''' - a layer of immature cells that differentiate to form either glial cells or neurons. The retina has two of these (an inner and outer).

'''Neuroectoderm''' - portion of the ectoderm that develops to form the central and peripheral nervous systems.

'''Optic chiasm''' - the point at which the optic nerves meet and cross over.

'''Optic cup''' - the structure that is formed after the optic vesicle folds in upon itself. This will form the retina.

'''Optic globe''' - a term that refers to the optic cup, lens vesicle and surrounding mesenchyme collectively.

'''Optic Nerve''' - The nerve which carries visual information from the retina to the brain for processing.

'''Optic placode''' - area of thickened ectoderm that gives rise to the lens of the eye.

'''Optic stalk''' - a long, narrow cavity that will produce the optic nerve.

'''Optic vesicle''' - a cavity that buds off from the neural tube and gives rise to the optic cup.

'''Posterior chamber'''- Fluid-filled area located between the iris and lens.

'''Pupil'''- opening in the anterior part of the eye, which controls how much light enters the eye.

'''Retina''' - Light-Sensitive portion located towards the back of the internal surface of the eye, which contains photoreceptors (rods and cones) which detects visual information and transmits it to the brain through the optic nerve.

'''Retinal bipolar cells''' - specialised neurons that transmit signals between the photoreceptors and ganglion cells in the retina

'''Retinal ganglion cells''' - transmit visual information from the retina to the brain

'''Sclera'''- white part of the external anterior surface of the eye, which envelopes the eyeball to give it support and protection of its internal contents.

'''Upstream genes''' - genes that activate one or more other "downstream genes".

'''Vascularise''' - to invade with blood vessels.

'''Vitreous Chamber'''- Area located between the lens and retina, which contains vitreous (a jelly like substance) whose function is to maintain the shape of the eye.

==Image Gallery==
<gallery>
Image:Eye_diagram_bandw.jpg‎ | Basic structure of the human eye.
Image:Eyediagramcolour1.JPG | Basic anatomy of the eye.
Image:Stage14 sem2b-limb.jpg | A Stage 14 embryo showing the location of an otic placode.
Image:Stage 13 image 060.jpg | A cross section showing the organisation of the developing brain, the optic vesicle and the lens (optic) placode.
Image:Formation of the optic vesicle 1.jpg | Early formation of the optic vesicle from the neural groove.
Image:Formation of the optic vesicle 2.jpg | The optic vesicle at a later stage, showing the optic stalk.
Image:Formation of the optic nerve and chiasm 1.jpg | A recognisable brain and eye structure in later development.
Image:Formation of the optic cup 1.jpg | Mechanism of optic cup formation.
Image:Formation of the optic cup 2.jpg | Layers of the optic cup in retina development.
Image:Formation of the retina 1.jpg | Cross-section of the primitive retina showing cell types and layers.
Image:Formation of the retina 2.jpg | Cross-section of a developed retina showing cell types and layers.
Image:Formation of the lens 1.jpg | The importance of the optic cup in lens differentiation.
Image:Formation of the lens 2.jpg | The lens placode separates from the ectoderm and migrates into the mesoderm forming the lens vesicle.
Image:Formation of the choroid and sclera 1.jpg | The choroid and sclera derives from mesenchyme surrounding the optic cup.
Image:Formation of the eyelid 1.jpg | Small grooves in the ectoderm of the head - the precursors to an eyelid.
Image:Formation of the eyelid 2.jpg | The eye at an advanced stage of embryonic development. Note however, that the eyelids remain fused until much later.
Image:Bionic_eye.JPG | An early prototype of the bionic eye.

</gallery>

==References==
<references/>

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--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

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{{2012Projects}}

2012 Group Project 1

2012-10-03T01:45:29Z

Z3254758: /* Image Gallery */

[[File:Eye_collage_2.jpg|right|830px]]

=Vision Development=

==Introduction==

Eyes are an important sensory organ shared across many different species and allow organisms to gather useful visual information from their environment. The visual system uses light from the environment and processes this information in the brain for visual perception. The visual system is complex, and is made up of various structures that work together to form vision. Each of the structures in the eye have specific tasks which contribute to the visual system. Knowledge of how the eye develops extends as far back as Aristotle more than 2000 years ago, and current knowledge shows that most of the crucial events of eye development occur in the embryological stage. The eye is an interesting model for studying the development of tissues in organisms, as it consists of cells from several parts of the embryo including the head ectoderm, neural ectoderm and mesoderm. From its many origins the cells come together and differentiate to produce the complex organ that is the eye. During this period there are many examples of inductive signaling, as the tissues coordinate their development throughout this elegant process.

The main anatomical structures of the eye are as follows:
{|
|
* Cornea

* Sclera

* Choroid

* Iris

* Ciliary body

* Lens

* Anterior chamber

* Posterior chamber

* Retina

* Optic nerve

|[[File:eye_diagram_bandw.jpg|right|250px|thumb|Basic structure of the human eye.]]
|[[File:Eye-pupil-sclera-iris.jpg|thumbnail|200px|Illustration of the front of the eye, showing the sclera, iris and pupil.]]
|}
[[File:Eyediagramcolour1.JPG|550px]]

==Research History==

=== '''Brief Timeline of Historical Developments on the Eye and its Embryology''' ===

{| width=800px
|-bgcolor="CEDFF2"
| width=100px|'''Time'''
| width=700px|'''Discovery'''

|-bgcolor="F5FAFF"
| '''Ancient Egyptians'''
| First to document cataracts. It is described as being 'the white disease of the eye' or 'darkening of the pupil.' <ref>Edwards, D.D. (1996). Ophthalmology before Hippocrates. In the History of Ophthalmology, ed. D.M. Albert and D.D. Edwards. Cambridge, Mass.: Blackwell Science.</ref> The Egyptians had some knowledge of the eye, however it is not known how much of the anatomy of the eye was known in their era.

|-bgcolor="CEDFF2"
| '''535 BC'''

|
Ancient Greek philosopher Alcmaeon conducted dissection of humans for the first time in recorded history. This included dissection of the eye. However, not much is known about which anatomical features he discovered. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17.">Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17.</ref>

|-bgcolor="F5FAFF"
| '''384- 322 BC'''

| [[File:Aristotle-eye.jpg|200px|thumbnail|The eye according to Aristotle.<ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "> Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau </ref> Note the lens is missing, and there are three vessels drawn that was believed to transport fluid to and from the eye.<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
]]
Aristotle performed dissections of animal embryos.<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

When Aristotle described the embryo of a ten day old chicken, he wrote "The eyes about this time, if taken out, are larger than beans and black; if their skin is removed the fluid inside is white and cold, shining brightly in the light, but nothing solid." <ref name="Magnus, H. (1998). Ophthalmology of the ancients. In J. Hirschberg (Ed.), The History of Ophthalmology: The monographs, Vol. 4, Part 1 (F.C. Blodi, Trans.) Bonn: Wayenborgh.">Magnus, H. (1998). Ophthalmology of the ancients. In J. Hirschberg (Ed.), The History of Ophthalmology: The monographs, Vol. 4, Part 1 (F.C. Blodi, Trans.) Bonn: Wayenborgh.</ref>

Aristotle believed that the eyes started forming during early embryogenesis, however, he also believed that the eyes are the last organs to form completely, and he incorrectly thought that the eyes shrink in later embryonic development. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press.">Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press.</ref> .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"

| '''340 BC'''

| Lens is thought to have been discovered by Hippocrates, due to his descriptions of the contents of the internal eye There has been studies in chick development later on by followers of Hippocrates. They claimed that eyes were visible in early embryogenesis. .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
|-bgcolor="F5FAFF"
|'''25 BC - 50 AD'''

| [[File:Celsus-eye.jpg|150px|thumb|The eye according to Celsus. <ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "/>
Note the lens is placed in the centre of the eye, in the vitreous.<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> ]]

Aulus Cornelius Celsus wrote a Roman medical text called 'De Medicina' in which he wrote that the lens was the part of the eye from which vision originated. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.">Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.</ref> Celsus also incorrectly drew the lens in the center of the globe in his diagram of the eye. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

|-bgcolor="CEDFF2"
| '''23-79 AD '''
|
Pliny the Elder said that the eye is the last of the organs to develop in the womb <ref name="Magnus, H. (1998). Ophthalmology of the ancients. In J. Hirschberg (Ed.), The History of Ophthalmology: The monographs, Vol. 4, Part 1 (F.C. Blodi, Trans.) Bonn: Wayenborgh."/>
|-bgcolor="F5FAFF"
| '''98-117 AD'''

| [[File:Rufus-eye.jpg|150px|thumb|The eye according to Rufus of Ephesus. <ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "/>
Note the lens is placed in the correct position, behind the iris of the eye <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> ]]

Rufus of Ephesus identified the lens as being located in the anterior part of the eye, close to the pupil. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

His diagram illustrates that he knew the correct position of the lens as being directly behind the iris, in the anterior part of the eye, and not in the centre as was previously depicted by others before him.

|-bgcolor="CEDFF2"
| '''130-200 AD'''

| [[File:Galen-eye1.jpg|150px|thumb|The eye according to Galen. <ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "/> ]]

Claudius Galen practised medicine in Rome. He wrote:

"1. Within the eye the principal orgran of sensation is the crystalline lens.

2. The sensation potential comes from the brain and is conducted via the optic nerves.

3. All other parts of the eyeball are supporting structures." <ref> Hirschberge, J. (1982). Antiquity, Vol. X in the History of Ophthalmology (F.C. Blodi, Trans.) Bonn: Wayenborgh. pp. 280 </ref>

Galen thought that the lens was produced from the vitreous. He also believed that the retina’s function was to give nourishment to the lens and vitreous, and to carry visual information to the brain from the lens. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

|-bgcolor="F5FAFF"

| '''1514-1564'''

| Andreas Vesalius published his anatomy book "De Humani Corporis Fabrica in 1543. He had the misconception that the lens was located in the centre of the eyeball. .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> He also wrote that the lens functioned "like a convex lens made of glass" <ref name="Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.">Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.</ref> pp. 48
|-bgcolor="CEDFF2"
| '''1535-1606'''

| Georg Bartisch correctly drew a diagram of the lens placed behind the iris in his book 'Ophthalmodouleia: das ist Augendienst'. <ref name="Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>
|-bgcolor="F5FAFF"

| '''1537-1619'''

| Fallopio Hieronymus Fabricius ab Aquapendente studied anatomy and embryology. He studied chicken embryos, and thought that chalazae (which comes from egg white) gives rise to the eyes. He also drew the lens directly behind the iris in a diagram in is book 'Tractatus de Oculo Visuque Organo. <ref name="Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

|-bgcolor="CEDFF2"
| '''1583'''

| Felix Platter published his book 'De corporis Humani Structura et Usu, after he performed dissections of human bodies. He believed that the retina is the primary visual organ in the eye. .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="F5FAFF"
| '''1619'''
| Scheiner is given credit to be the first person to correctly draw the diagram of the anatomy of the eye. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
|-bgcolor="CEDFF2"
| '''1672'''
| Marcello Malpighi described the embryonic development of the chicken. He drew many detailed diagrams of the chick eye. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1665'''
| Nicolaus Steno identified the choroid fissure in his study of a developing embryo of a chicken. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="CEDFF2"
| '''1754'''

| Albrecht von Haller studied the embryology of the eye. With help from his student Johann Gottfried Zinn, he contributed to the understanding of the development of the ciliary body, ciliary zonule, and their relationship with the lens and vitreous. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1817'''

| Christian Pander discovered the three embryonic germ layers, which he wrote about in his book. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/> Pander was the first to think of 'the optic vesicles as lateral evaginations' of the 'prosencephalon'; however, he was incorrect about the details regarding how 'the eye develops from these evaginations'. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="CEDFF2"
| '''1828-1837'''

| Karl Ernst von Baer studied embryology. He discovered that the optic vesicles were 'outgrowths of the embryonic forebrain' <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> which he believed was caused by pressure from fluids in the central nervous system. Von Baer also believed that the optic vesicle opens to form the pupil, and that fluid in the optic vesicle coagulates to form the vitreous body and lens. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1830'''

| Emil Huschke discovered that the lens forms from the invagination of the surface ectoderm. He concluded that the lens hence does not form ‘from the fluid of the optic vesicle’ <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> as previously thought.
|-bgcolor="CEDFF2"
| '''1832'''

| Emil Huschke wrote in his manuscript ‘Ueber die erste Entwinkenlung des Auges und die damit zusammenhängende Cyklopie’ that the lens capsule forms from the outer surface ectoderm, which detaches and moves back inward, which is later enclosed again by several membranes, such as by the cornea. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

Huschke also described how the optic cup and choroid fissure forms. He discovered that the optic vesicles are produced from the two-layered optic cup. However, he incorrectly described the destiny of the ‘individual optic cup layers’. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

|-bgcolor="F5FAFF"
| '''1838'''
| Matthias Jakob Schleiden and Theodor Schwann formulated the ‘cell theory’: “All living things are formed from cells, the cell is the smallest unit of life, and cells arise from pre-existing cells.” <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
|-bgcolor="CEDFF2"
| '''1839'''

| Theodor Schwann contributed a better understanding of the development of the lens through studying the foetus of a pig, which he wrote about in his book ‘Mikroskopische Untersuchungen Über Die Uebereinstimmung in Der Struktur Und Dem Wachsthum Der Thiere Und Pflanzen’. He wrote that the lens is made of ‘concentric layers’ of fibres which proceeds from an anterior to posterior direction. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1842'''
| Robert Remak gave the current names to the three embryonic germ layers: ectoderm, mesoderm and endoderm. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"
| '''1843'''
| Wilhelm Werneck published his book ‘Beiträge zur Gewebelehre des Kristallkörpers’. He wrote that the contents inside of the lens is not made of fluids, as was previously believed. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/> Werneck also discovered that the fibers of the lens continues to grow from the outside to the centre during embryogenesis. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

|-bgcolor="F5FAFF"
| '''1855'''

| Robert Remak wrote his book ‘Untersuchungen über die Entwickelung der Wirbelthiere’. He wrote about what he discovered in his studies of the development of the eye in the embryos of chickens, frogs, and rabbits. He wrote very descriptively about the embryology of lens formation, amongst other topics. He discovered that the ectoderm gives rise to the lens placode. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

|-bgcolor="CEDFF2"
| '''1858'''
| Henry Gray published his book 'Anatomy, Descriptive and Surgical'. He had also previously studied the embryonic development of the optic nerve and retina of chickens.
|-bgcolor="F5FAFF"
| '''1877'''
| Paul Leonhard Kessler wrote about the embryonic development of the lens in mice in his book ‘Zur Entwickelung des Auges der Wirbelthiere. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"
| '''1891'''
| Vincenzo Colucci studied newts and discovered their ability to regenerate the lens.<ref> Tsonis, P. A. (2001). Regeneration of the Vertebrate Lens and Other Eye Structures. eLS. (Online Publication). DOI: 10.1038/npg.els.0001102 </ref>
|-bgcolor="F5FAFF"
| '''1892'''
| Dr. Oscar Hertwig published his book ‘Text-Book of the Embryology of Man and Mammals. <ref> Hertwig, O. Text-book of the embryology of man and mammals. S. Sonnenschein 1901. (Translated from the 3d German ed. by Edward L. Mark.) </ref> It contains a very detailed description of the development of the eye, according to the findings at that time. [http://embryology.med.unsw.edu.au/embryology/index.php?title=Book_-_Text-Book_of_the_Embryology_of_Man_and_Mammals_16-2#The_Development_of_the_Eye]
|-bgcolor="CEDFF2"
| '''1895'''
| Gustav Wolff also independently studied newts and discovered their ability to regenerate the lens. .<ref> Tsonis, P. A. (2001). Regeneration of the Vertebrate Lens and Other Eye Structures. eLS. (Online Publication). DOI: 10.1038/npg.els.0001102 </ref>

|-bgcolor="F5FAFF"

| '''1900'''
| Carl Rabl published his book ‘Uber den Bau und die Entwicklung der Linse’. He wrote about the development of the lens in mammals, fish, birds, reptiles, and amphibians. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"
| '''1901'''
| Hans Spemann published his findings from his experimental studies about the formation of the lens in the frog. He found that the optic cup needed to be in contact with the ectoderm for normal development of the eye. <ref> Spemann, H. (1901). Über Correlationen in der Entwicklung des Auges. Verhand. Anat. Ges. 15: 61-79. </ref> <ref> Saha, M. (1991). Spemann seen through a lens. In Gilbert, S. F. (ed.). A Conceptual History of Modern Embryology. Plenum Press, NY. pp. 91-108.</ref>
|-bgcolor="F5FAFF"
| '''1906'''
| Brown ‘s book “The Embryology Anatomy and Histology of the Eye” was published. It contained detailed descriptions of the embryonic development of the eye according to the knowledge current at that time, mainly based on observations from embryos of rabbits and chickens. <ref> Brown, E.J. (1906). The Embryology Anatomy and Histology of the Eye. Chicago: Hazlitt & Walker. 1906 </ref>

|-bgcolor="CEDFF2"
| '''1907'''

| John Clement Heisler published his book ‘A Text-book of embryology’. It contains a chapter detailing the embryonic development of the eye, according to the knowledge current at that time. The book’s copyright has expired, so it can be viewed free online: [http://archive.org/details/atextbookembryo01heisgoog]

Julius Kollman also published his book 'Atlas of the Development of Man'. It contained very detailed description and illustrations showing the embryonic development of the human according to the knowledge current at that time. His illustrations were reused by many others after his time and built upon for further refined understanding of the embryology of the human.

Here are examples of Julius Kollman's excellent illustrations showing eye development in various stages:

'''Formation of Primary Optic Vesicle:'''
<gallery>
File:Kollmann691.jpg|The blue part at the bottom is the endoderm. The pink middle layer is the mesoderm. The top yellow layer is the ectoderm. The fold labelled as 'augenfeld' is the place where the optic vesicle will form.
File:Kollmann692.jpg|The eye area (augenfeld) is a bowl shaped bulge still located on the side walls.
File:Kollmann693.jpg| The neural tube is shown after removal of all of the ectoderm and ventral organs, such as heart, gut tube, etc. The primary optic vesicle forms a slightly flattened hollow protrusion on the forebrain.
File:Kollmann694.jpg|The lateral surface of the primary optic vesicle is slightly depressed, showing the first sign of the emergence of the secondary optic vesicle
</gallery>

'''Development of Lens:'''

<gallery>
File:Kollmann695.jpg|The bulging lateral wall of the primary optic vesicle is covered by a fairly well demarcated lens plate, a direct continuation of the ectoderm. Between the optic vesicle and the lens pit are some flattened spindle-shaped cells. In the adjoining mesoderm are cross-sections of capillaries.
File:Kollmann697.jpg|The lens still hangs together with the ectoderm. The primary eye vesicle is indented with respect to the lens. Between the lens and the lateral plate of the optic vesicle is a narrow space, which allows area to further develop later.
File:Kollmann698.jpg|4th Week of development. The internal organisation shows the secondary optic vesicle. A: The rear wall of lens is noticeable and is enveloped by mesoderm. B: The edges of the lens pit is already grown and the lens vesicles are formed, which is still related to the remaining ectoderm.
File:Kollmann699.jpg|The lens has now cut off from the ectoderm, but is still very superficial. Between it and the lateral lamina of the optic cup, there is a considerable space. The eye stalk has become longer and is enclosed together with the optic cup and lens of the mesoderm. The cornea, sclera and choroid make gradual development.
</gallery>

|-bgcolor="F5FAFF"

| '''1921'''
| Bailey and Miller published their textbook “Text-Book of Embryology “. <ref> Bailey, F.R. and Miller, A.M. (1921). Text-Book of Embryology. New York: William Wood and Co. (Note- This book is only at an early edited stage)</ref> It contains detailed description of the development of the embryonic eye according to the knowledge current at that time. [http://embryology.med.unsw.edu.au/embryology/index.php?title=Book_-_Text-Book_of_Embryology_18]

|-bgcolor="CEDFF2"
| '''1925'''

| Mann published his research article, in which he gives a detailed account of the development of the human iris. He divided the development of the iris into four stages: weeks 4-7 (before the ectodermal iris forms or before the anterior chamber forms); weeks 7-11 (anterior chamber appears, and mesodermal iris forms); weeks 11-12 (ectodermal iris forms); 3-8 months (muscles of the pupil forms from ectodermal iris, and the central portion of the mesodermal iris atrophies to make the pupil clear). <ref name="PMID18168466"><pubmed>18168466</pubmed></ref>
O Leser also published an article detailing the development of extraocular muscles in mammals he studied. <ref name="PMID18168498"><pubmed>18168498</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1939'''
| Holtfreter <ref> Holtfreter, J. (1939). Gewebeaffinitat, ein Mittel der embryonalen
Formbildung. Arch. Exp. Zellforsch. 23, 169-209. </ref> studied amphibians and observed that that the development of the eye stops at the ‘optic vesicle stage’ if there is no contact ‘with the epidermis and neural crest driven mesenchyme’. <ref name=”PMID11023863”><pubmed>11023863</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1955'''
| Barber published his book ‘Embryology of the human eye’. <ref> Barber AN: Embryology of the human eye. St. Louis. CV Mosby 1955</ref> In contains detailed descriptions of the embryological development of the human eye according to the knowledge current at that time. It contains many photographs of the eye at different stages of development.

|-bgcolor="F5FAFF"
| '''1957'''
| Coulombre studied a chicken embryo to find the role of intraocular pressure in the development of the chick’s eye, especially in regards to its control of the size of the eye structures. <ref name="PMID13469954"><pubmed>13469954</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1958'''
| Coulombre studied the development of the cornea and how it develops its transparency. <ref name="PMID13563560"><pubmed>13563560</pubmed></ref> He also studied the development of corneal curvature. <ref name="PMID 13519969"><pubmed> 13519969</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1962'''
| Coulombre studied the development of the conjunctival papillae and scleral ossicles. <ref name="PMID 14023393"><pubmed> 14023393</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1963'''
| Coulombre studied the development of lens fibers and their orientation. <ref name="PMID14077035"><pubmed>14077035</pubmed></ref> He also studied the development of pigmented epithelium. <ref name="PMID14023394"><pubmed>14023394</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1964'''

| Coulombre further studied the development of the lens to determine the role of the lens in eye growth. <ref name="PMID14189921"><pubmed>14189921</pubmed></ref> He also studied the role of thyroid in the development of the cornea and the development of corneal transparency. <ref name="PMID14211912"><pubmed>14211912</pubmed></ref> Mann also published his work called ‘The development of the human eye’, which contains detailed description of the embryonic development of the eye according to current knowledge at that time. <ref> Mann I. The development of the human eye. New York: Grune and Stratton 1964</ref>

|-bgcolor="CEDFF2"
| '''1965'''
| Coulombre published his findings regarding the regeneration of the neural retina from pigmented epithelium in the embryo of chickens. <ref name="PMID5833111"><pubmed>5833111</pubmed></ref> Smelser also published his findings on the embryological development and morphology of the lens. <ref name="PMID14340157"><pubmed>14340157</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1966'''

| Formation of the face and orbit occurs from the differentiation of neural crest cells. <ref name="PMID5969670"><pubmed>5969670</pubmed></ref> O’Rahilly also published findings of the development of the eye in the early stages of human embryos. <ref> O'Rahilly, R. 1966 The early development of the eye in staged human embryos. Contr. Embry. Carnegie Inst., Wash., 38: 1–42</ref>

|-bgcolor="CEDFF2"
| '''1968'''
| Findings of the postnatal development of the retina of rats was published. <ref name="PMID5640327"><pubmed>5640327</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1969'''

| Mann again published his work called ‘The development of the human eye’. He stated that that the lens in humans forms completely from the ectoderm. <ref name=”Mann I. The Development of the Human Eye. New York, USA: Grune & Stratton, Inc; 1969”> Mann I. The Development of the Human Eye. New York, USA: Grune & Stratton, Inc; 1969</ref> Coulombre also studied the development of the lens, and took note of its size, shape and orientation throughout its developmental stages. <ref name="PMID 5772716"><pubmed> 5772716</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1970'''
| Coulombre again further studied the regeneration of the neural retina from pigmented epithelium of embryos of chickens. <ref name="PMID 5472476"><pubmed> 5472476</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1971'''

| Coulombre further studied the development of the lens. This time he focused on analysing the histological mechanisms in the reconstitution of the lens from implanted lens epithelium. <ref name="PMID 4925671"><pubmed> 4925671</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1973'''
| A research article was published, detailing the embryonic development of the retina of humans. <ref name="PMID 6650859"><pubmed> 6650859</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1976'''

| Geeraets published his observations of the closure of the embryonic optic fissure in golden hamsters, using the electron microscope. <ref name="PMID 1266776"><pubmed> 1266776</pubmed></ref> Kornneef also published an article based on his studies of the development of connective tissue in the human orbit. <ref name="PMID 1020699"><pubmed> 1020699</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1981'''
| A research article was published detailing how myelin forms in the optic nerve of humans. <ref name="PMID 7224936"><pubmed> 7224936</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1983'''
| O’Rahilly’s further research developments was published, reporting the timing and sequence of events in the development of the embryonic human eye. <ref name="PMID 6650859"><pubmed> 6650859</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1990'''

| Van Driell et al. <ref>Driell, D. Van; Provis, J.M.; Billson, F.A.: Early differentiation of ganglion, amacrine, bipolar and Muller cells in the developing fovea of the human retina. J. Comp. Neurol. 291: 203-219.</ref> studied the manner in which amacrine, bipolar, retinal ganglion cells, and Muller cells differentiate in the developing fovea of the retina of a 15-week old human foetus. <ref name="PMID1628748"><pubmed>1628748</pubmed></ref> Tripathy also published an article providing evidence that the lacrimal glands in humans originates from the neuroectoderm. <ref name="PMID2406219"><pubmed>2406219</pubmed></ref>

|}

==Development, Structure and Function of Ocular Components==

The eye itself is formed from several components; notably the optic placode of the head ectoderm, the optic vesicle from the neural tube, and mesenchyme from the mesoderm and neural crest cells. The optic placode contributes the lens to the eye, the optic vesicle gives rise to layers of the retina, while the mesenchyme will produce the ciliary body, iris, choroid and sclera.<ref>http://www.vetmed.vt.edu/education/curriculum/vm8054/eye/EMBYEYE.HTM</ref> Cells from the neural tube will also produce the optic nerve, which receives nerve impulses from the retina of the eye. Eyes initially form as laterally paired structures and migrate medially in the human embryo. In other animals such as birds and lizards, the eyes do not migrate and develop laterally on the head. The optic placodes become prominent on the surface of the embryo at approximately Stage 14 of development.

[[File:Stage14 sem2b-limb.jpg|200px|thumb|left|A Stage 14 embryo showing the location of an otic placode.<ref name="http://embryology.med.unsw.edu.au/embryology/index.php?title=ANAT2341_Lab_6_-_Early_Embryo">http://embryology.med.unsw.edu.au/embryology/index.php?title=ANAT2341_Lab_6_-_Early_Embryo</ref>]] [[File:Stage 13 image 060.jpg|400px|thumb|center|A cross section showing the organisation of the developing brain, the optic vesicle and the lens (optic) placode.<ref name="http://embryology.med.unsw.edu.au/embryology/index.php?title=ANAT2341_Lab_6_-_Early_Embryo"/>]]

===Optic Nerve===

The optic nerve consists of nerve fibres that transmit information from the retinal photoreceptor cells to the brain. The optic nerve is formed from the optic stalk, which develops as the optic vesicle migrates from its origin in the neural tube to its destination - the surface ectoderm - where it will fuse with the optic placode (also known as the lens placode, which will contribute the lens to the eye).<ref name="PMID11687490"><pubmed>11687490</pubmed></ref>

[[File:Formation of the optic vesicle 1.jpg|400px|thumb|left|Fig. 1: Early formation of the optic vesicle from the neural groove.]] [[File:Formation of the optic vesicle 2.jpg|400px|thumb|center|Fig. 2: The optic vesicle at a later stage, showing the optic stalk.]]

As can be seen in Figure 1 above, the optic vesicle forms from the neural tube. However, note that the neural tube has not yet closed, and is still the neural groove at this point. Figure 2 then shows the optic vesicle at slightly later stage in the same simplified cross-section of the embryo, as it migrates from the neural tube to the surface ectoderm. Note the presence of the optic stalk which links the optic vesicle to the neural tube. Later in development, this primitive structure will become the optic nerve, which will link the eye to the brain.

The nerve fibres themselves will initially originate from the retinal ganglion cells in the eye during week 6.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008">Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008</ref> After two weeks, these fibers will have grown along the inner wall of the optic stalk and have reached the brain. They grow both in length and width, with the nerve fibres filling the hollow optic stalk to form the solid optic nerve. More than one million nerve fibers will eventually make up the optic nerve, along with glial cells which arise from the inner wall of the optic stalk itself.<ref><pubmed>1451666</pubmed></ref> Myelinisation of the optic nerve begins much later in development at around 7 months, beginning at the optic chiasm and moving towards the eye.<ref><pubmed>7224936</pubmed></ref> The optic chiasm forms just before the nerves reach the brain, and is where half the nerve fibres from each eye will cross over to the opposite side of the brain. This is demonstrated in Figure 3. Note the crossing over of the optic nerves just before they enter the brain, at the optic chiasm. This organisation is now much more familiar, with the eyes near the ectoderm and the optic nerve leading through the mesoderm to the brain buried deep in the embryo.

[[File:Formation of the optic nerve and chiasm 1.jpg|400px|thumb|center|Fig. 3: A recognisable brain and eye structure in later development.]]

===Retina===

The retinal component of the eye is formed when the optic vesicle folds in upon itself, forming the optic cup (see Figure 4). In doing so it creates two layers - an inner wall and an outer wall of the optic cup (Figure 5). These two layers of the optic cup will give rise to the two layers of the retina - the inner neural retina, and the outer pigmented epithelium.<ref name="PMID11687490"/> Note the existence of the space between the two layers of the retina. This is known as the intraretinal space and disappears by the 7th week of development, however the two layers never completely fuse and can become separated as a result of physical trauma to the head - leading to a detached retina and loss of vision.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/>

The inner wall of the optic cup, which will give rise to the neural retina, consists of a layer of pseudostratified cells (see Figure 6) that later differentiate into rod, cone, bipolar, ganglion, horizontal, amacrine and glial cells of the retina (Figure 7).<ref name="PMID18168748"><pubmed>18168748</pubmed></ref> The outer wall of the optic cup consists of a layer of cuboidal cells that contain melanin - the light absorbing pigment. The function of this layer is to absorb light and prevent internal reflection of light within the eye, which would impair our ability to form distinct images. Interestingly, in some animals such as cats, this layer actually reflects light intentionally to increase the amount of light available to the eye in low-light conditions. This is why cats seem to have eyes that glow in the dark.<ref>http://dialspace.dial.pipex.com/agarman/bco/fact4.htm</ref>

[[File:Formation of the optic cup 1.jpg|400px|thumb|left|Fig. 4: Mechanism of optic cup formation.]] [[File:Formation of the optic cup 2.jpg|400px|thumb|center|Fig. 5: Layers of the optic cup in retina development.]]

The inner wall itself is divided into two components - the inner neuroblastic layer and the outer neuroblastic layer (see Figure 6). The outer neuroblastic layer forms the rod and cone cells while the inner neuroblastic layer forms the remaining cell types found in the retina - the bipolar, ganglion, horizontal, amacrine and glial cells (Figure 7).<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/> The organisation of the retina is interesting in that incoming light passes through several layers of these neural retina cells before it is detected by rod and cone cells at the back of the retina, and then nerve signals are passed back through the layers of neural retina cells that the light just passed through moments before - a seemingly strange design that the eye does not share with man-made light-capturing devices such as a camera (imagine putting the wires in front of the image sensor!).

Differentiation of the neuroblastic layers into neural retina cells occurs in a pattern both within the layers and across the retina. Cells differentiate from the inner neuroblastic layer to the outer neuroblastic layer, and differentiate from the central retina to the peripheral retina.<ref name="PMID18168748"/> The macula is first identifiable in week 22 when ganglion cells start to form multiple rows, and the primitive fovea begins to form at approximately the same time as a depression in the macula.<ref><pubmed>6462623</pubmed></ref> It is not until 15-45 months after birth that this area becomes exclusively populated by cone cells and becomes the fovea centralis - the area of the retina with the highest visual acuity.

[[File:Formation of the retina 1.jpg|400px|thumb|left|Fig. 6: Cross-section of the primitive retina showing cell types and layers.]] [[File:Formation of the retina 2.jpg|400px|thumb|center|Fig. 7:Cross-section of a developed retina showing cell types and layers.]]

===Ciliary Body===

The ciliary body consists of ciliary processes and three portions of fibres that constitute the ciliary muscles. It functions to maintain normal eye physiology as well as playing a direct role in accommodation.

During development, the ciliary processes form slightly posterior to the iris, developing from part of the anterior rim of the optic cup. It is thought that the folded structure of the ciliary processes is brought about by intraocular pressure and specific signalling pathways.<ref name="PMID16959249"><pubmed>16959249</pubmed></ref> While the ciliary muscles and the endothelial cells of the ciliary blood vessels are chiefly formed by mesenchymal cells<ref><pubmed>16249499</pubmed></ref>, the neural crest and neuroectoderm also contribute to their development.<ref><pubmed>12127103</pubmed></ref> The normal development of the ciliary body is dependent on the correct expression of bone morphogenetic protein (BMP)-4, which is a member of the transforming growth factor-β superfamily.<ref><pubmed>1222340</pubmed></ref> Napier and Kidson (2007) summarised numerous genes that have been associated with ciliary body development, however their direct roles have not been well documented.<ref name="PMID16959249"/>

===Iris===

The iris is a thin layer that develops at the end of the third month of development and is derived from the anterior rim of the optic cup. The stroma of the iris develops from cells of neural crest cell origin.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/> The muscles that are responsible for the dilation and constriction of the pupil (dilator pupillae and sphincter pupillae muscles) form from the neuroectoderm of the optic cup. These cells are initially epithelial cells that then transform into smooth muscle cells. <ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"></ref>. The invagination of the optic vesicle which creates the optic cup, also causes the formation of the optic cup lip. This is the region of the where the epithelium doubles back, separating the outer pigmented layer and the inner nonpigmented layer. This is the edge of the iris that borders on the pupil<ref><pubmed> Retinal and anterior eye compartments derive from a common progenitor pool in the avian optic cup</pubmed></ref>.

The final colour of the iris is not evident until the postnatal period. It is determined by a number of genes including IRF4, SLC24A4 and MATP<ref><pubmed>19710684</pubmed></ref>. Other features such as crypt frequency, furrow contractions, presence of peripupillary pigmented ring, and number of nevi also become evident during development<ref><pubmed>21835309</pubmed></ref>. Mutations in Pax6 have been shown to cause partial or complete loss of the iris <ref><pubmed>12386935</pubmed></ref>.

===Cornea===

The cornea is the transparent, avascular, most anterior portion of the eye. It is responsible for conducting light into the eye and focusing it on to the retina, as well as maintaining the rigidity of the eyeball. It consists of 5 layers- the epithelium, Bowman’s layer, stroma, Descemet’s membrane and the endothelium.

The epithelium and endothelium of the cornea first appear during the 5th week of gestation. The epithelium of the external surface of the cornea is derived from surface ectoderm, while the mesenchyme is derived from the mesoderm<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"/>. The endothelium is a two-cell cuboidal layer which is made up of differentiated neural crest cells that were initially from the optic cup. By week 8 the endothelial cells begin to secrete a basement membrance which later forms Descemet’s membrane<ref><pubmed>6511224</pubmed></ref>. At approximately 16 weeks gestation the Bowman’s membrane begins to form from the thickening of the stroma that is located under the corneal epithelium<ref>Riordan-Eva P, Whitcher JP. Vaughn and Asbury's General Ophthalmology, Lange Medical Books/McGraw Hill. 2004:25–27</ref>. During the third month glycosaminoglycans secreted by fibroblasts form the ground substance of the cornea, with collagen fibrils and keratan sulphate also appearing around this time. Shortly after this tight junctions form between the endothelial cells<ref><pubmed>19481138</pubmed></ref>. Fibroblast growth factor causes the epithelial cells to proliferate<ref><pubmed>20105280</pubmed></ref>.

Towards the end of the gestational period the cornea becomes larger due to the production of aqueous humor<ref>Yanoff M, Duker JS. Ophthalmology. Mosby; St. Louis, MO: 2004</ref>. The final transparent structure develops because hyaluronidase removes hyaluronic acid, thyroxine causes dehydration of the stroma, and the entire structure becomes avascular<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/>. Numerous genes have been implicated in the development of the cornea, these include, but are not limited to, PAX6, PITX2, FOXC1, MAF, TMEM114, SOX2, OTX2 and BMP4<ref><pubmed>18637741</pubmed></ref>. Pax6 and Pax6(5a) isoforms are essential for the normal development of the eye. Over or under expression can both lead to major structural abnormalities<ref><pubmed>18386822</pubmed></ref>.

===Lens===

The lens has its origin from the optic placode, which develops on the ectodermic surface of the embryo and migrates both medially and inwards into the embryo. The lens allows accommodation of the eye, and adjusts its thickness in order to focus on near or far objects. The study of lens development was one of the first to highlight the importance of inductive signaling in development, with Spemann's pioneering work at the start of the 20th century, finding that the absence of retinal development resulted in the absence of lens formation.<ref name="PMID11687490"/> Indeed, it has been consistently shown that the interaction of the migrating optic vesicle with the surface ectoderm of the head is vital in producing differentiation of the lens.<ref name="PMID15558475"><pubmed>15558475</pubmed></ref> The mechanism of interaction is complex but basically involves upstream genes switching on downstream genes, with the genes eventually producing specialised proteins which constitute the lens. The whole process starts with the signaling molecules from the optic cup initiating a thickening of the surface ectoderm of the head (Figure 8). It is thought that this region of specific ectoderm is responsive to the signaling molecules, as lens formation is incomplete or absent when ectoderm from the lateral portion of the embryo (i.e. non-head ectoderm) is exposed to the same inductive signaling processes.<ref name="PMID9216064"><pubmed>9216064</pubmed></ref> Pax6 has been shown to be one of the major genes required for differentiation of the lens, which in turn switches on transcriptional genes such as Sox 1, 2 and 3 among others - producing water-soluble proteins called crystallins - responsible for giving the lens its transparency and refractive properties.<ref name="PMID9609835"><pubmed>9609835</pubmed></ref>

[[File:Formation of the lens 1.jpg|400px|thumb|left|Fig. 8: The importance of the optic cup in lens differentiation.]] [[File:Formation of the lens 2.jpg|400px|thumb|center|Fig. 9: The lens placode separates from the ectoderm and migrates into the mesoderm forming the lens vesicle.]]

The lens placode invaginates from the head ectoderm and migrates into the mesoderm (Figure 9). Once this structure (now known as the lens vesicle) is in place opposite the optic cup, the combined structure is referred to as the optic globe and resembles a recognisable eye structure. The lens continues to differentiate further, as mentioned above, through the formation of crystallin proteins, which give the lens its unique properties and allows for the fine control over the degree of refraction that takes place.

===Aqueous Chambers===

There are both anterior and posterior aqueous chambers of the eye which contain aqueous humour. A space develops in the mesenchyme situated between the lens and cornea to form the anterior aqueous chamber. The mesenchyme located superficially to this chamber forms the mesothelium as well as the transparent portion of the cornea.

The posterior chamber develops from a similar space in the mesenchyme, however it is located between the iris and the lens. The anterior and posterior chambers are able to communicate with one another once the papillary membrane vanishes and the pupil is formed. This channel is known as the scleral venous sinus.<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011">Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011</ref>

Contained within the aqueous chambers is aqueous humor. The production of aqueous humor is dependant on the development of the ciliary body. It is produced in the ciliary processes and it’s production is a metabolic process driven by the delivery of oxygen and the removal of wastes via the ciliary circulation<ref><pubmed>20801226</pubmed></ref>.

===Choroid and Sclera===

The choroid and sclera are adjacent layers that surround the eye and act to vascularise and protect the eye respectively. They are formed from neural crest and mesoderm-derived mesenchyme which condenses around the optic cup and lens vesicle between weeks 5 and 7 of development to form a primitive eyeball structure known as the optic globe.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/> Blood vessels first start to appear in the choroid layer at approximately week 15, and arteries and veins can be distinguished by week 23.<ref>Development of the Choroid and Related Structures, K. Sellheyer, Eye (1990) 4, 255-261</ref> Inductive processes are thought to play a vital role during formation of the choroid and sclera; with the retinal pigmented epithelium inducing differentiation of the surrounding mesenchyme while at the same time the neural crest-derived mesenchyme contributing components to the retinal pigmented epithelium such as melanocytes.<ref name="PMID1628748"/> In addition to having functional roles themselves, the primitive choroid and sclera also contribute components to the developing ciliary body and cornea (Figure 10). In the adult eye, the choroid is continuous with the ciliary body and the sclera with the cornea.

[[File:Formation of the choroid and sclera 1.jpg|400px|thumb|center|Fig. 10: The choroid and sclera derives from mesenchyme surrounding the optic cup.]]

===Eyelids===

The eyelids are ectodermal and mesodermal in origin and are an extension of the skin which covers and protects the eye. The surface ectoderm gives rise to the conjunctiva, skin epithelium, hair follicles, cilia, Zeis glands, glands of Moll, and meibomian glands. <ref name=" Cook CS, Ozanics V, Jakobiec FA. (1994) Prenatal development of the eye and its adnexa. In Tasman W, Jaeger EA, editors: Duane’s foundations of clinical ophthalmology, vol 1, Philadelphia, 1994, Lippincott. "> Cook CS, Ozanics V, Jakobiec FA. (1994) Prenatal development of the eye and its adnexa. In Tasman W, Jaeger EA, editors: Duane’s foundations of clinical ophthalmology, vol 1, Philadelphia, 1994, Lippincott. </ref> The mesenchyme gives rise to the tarsal plates, levator muscles, orbicularis muscles, and tarsal muscle of Muller. <ref name=" Cook CS, Ozanics V, Jakobiec FA. (1994) Prenatal development of the eye and its adnexa. In Tasman W, Jaeger EA, editors: Duane’s foundations of clinical ophthalmology, vol 1, Philadelphia, 1994, Lippincott. "/> Eyelid formation can be first noted during week 5 when small grooves develop in the surface ectoderm (Figure 11).<ref><pubmed>7364662</pubmed></ref> These small grooves deepen and extend into the mesoderm and the primitive eyelid structures grow towards one another, eventually fusing together during week 8.<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"/> It is not until week 26-28 that the eyelids will separate again. The anterior surface of the eyelid becomes covered by two layers of epithelium; this forms the epidermis of the eyelids. <ref name="Kikkawa DO, Lucarelli MJ, Shovlin JP, et al: Ophthalmic facial anatomy and physiology. In Kaufman PL, Alm A, editors: Adler’s physiology of the eye, St Louis, 2003, Mosby, pp 16."> Kikkawa DO, Lucarelli MJ, Shovlin JP, et al: Ophthalmic facial anatomy and physiology. In Kaufman PL, Alm A, editors: Adler’s physiology of the eye, St Louis, 2003, Mosby, pp 16.</ref> Tarsal plates then begin to develop, which eventually leads to the formation of meibomian glands. <ref name="PMID1628748"/> The ectoderm reflects over the developing cornea to form the conjunctival sac, a space that is filled by secretions from the lacrimal gland in order to allow smooth motions of the eyelid over the eye and also to clean the cornea and prevent accumulation of particles on the eye that may disrupt vision. By the time the eyelids separate, the eye has all its major components present (Figure 12), and further development consists mainly of growth and vascularisation.

[[File:Formation of the eyelid 1.jpg|400px|thumb|left|Fig.11: Small grooves in the ectoderm of the head - the precursors to an eyelid.]] [[File:Formation of the eyelid 2.jpg|400px|thumb|center|Fig. 12: The eye after week 8 of development. Note however, that the eyelids remain fused until weeks 26-28.]]

===Lacrimal Glands===

There are three stages of lacrimal gland development. The first is the presumptive glandular stage in which the superior conjunctival fornix epithelium thickens and the surrounding mesenchymal cells condense. These mesenchymal cells are of neural crest origin<ref><pubmed>9882499</pubmed></ref>. The second stage sees the development of nodular formations around the superior conjunctival fornix and the formation of lumina within the epithelial buds, this stage is therefore known as the bud stage. Innervation and vascularisation also occur during this stage. The final morphological changes occur during the glandular maturity stage which occurs in weeks 9-16 when the lacrimal glands begin to resemble the mature glands. During the 13th week the lacrimal and zygomatic nerves anastomose<ref><pubmed>14635806</pubmed></ref>.

These glands are responsible for the production of tears however they do not start to function until 1-3 months after birth. The mature lacrimal gland is made up of two lobes- the palpebral and orbital lobes.

==Current Research==

Not only are there still many important processes and components of eye development that we would like to understand, this knowledge also contributes to the development of treatments for eye disorders and technologies such as the bionic eye.

===The impact of visible light on the immature retina===

<pubmed>22405869</pubmed>

The authors mentioned in this article <ref name="PMID22405869"><pubmed>22405869</pubmed></ref> that they were interested in investigating the effect of light on postnatal eye development in mice, because mice are born with fused eyelids, which separate 12 days after birth. Before the eyelids separate, the retina develops in mice with very little radiation from light. It is believed that the darkness plays a role in the development of the retina in mice, which is why their eyelids are fused for 12 days after birth. Therefore the authors were interested to see what effect light would have on postnatal retinal development of mice, with special interest in retinal ganglion cells (RGC). In their experiment, they surgically opened the eyelids on the right eyes of some of the mice to expose them to visible light 12 hours per day, while they left some other mice in the dark after surgical separation of their eyelids. They also kept the left eyes of the mice naturally fused as controls in the experiment. Their results showed that early light exposure in mice causes a decrease in retinal ganglion cells because it affects cellular apoptosis in the retina. The authors also observed that early exposure to light in mice causes lumican mRna transcription to resume and to quickly increase. (Lumican normally stays silent in retina after birth).

---------

===GABA Maintains the Proliferation of Progenitors and Non-Pigmented Ciliary Epithelium===

<pubmed>22590629</pubmed>

{| width=800px
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|-
| GABA is an ‘inhibitory neurotransmitter’ in the central nervous system of adults. <ref name="PMID22590629"><pubmed>22590629</pubmed></ref> It is responsible for controlling proliferation of stem cells and progenitor cells. The authors of this article <ref name="PMID22590629"/> was interested to find the effects of GABA on proliferation of progenitor cells and non-pigmented ciliary epithelial cells (NPE) in the retina. Their study focused on progenitor cells and non-pigmented epithelium of the ciliary body in chickens. Non-pigmented epithelial cells in chickens arise from the neuroepithelium of the optic cup. They share similar functions as progenitors of the early retina, such as expression of Chx10 and Pax6 genes. It is not agreed upon whether epithelial cells of the ciliary body have stem cell properties. However, it has been found that these cells can be cultured and transplanted into retinas that are injured, in order to replace neurons that were previously lost. However, there is not much known about what factors regulate the proliferation of stem cells. Hence the authors were interested in finding the effects of GABA on proliferation of retinal cells. Their results showed that non-pigmented epithelial cells in chickens ‘express extrasynaptic-like GABAA receptors’ that have the ability to regulate cell proliferation. It has been found that inhibiting these ‘GABAA receptors’ also causes a decrease in proliferation of retinal progenitor cells and non-pigmented epithelial cells in 'the intact E8 retina’. <ref name="PMID22590629"/>

|
[[File:Gaba-effects-retina.JPG|thumbnail|250px|'''GABAA receptor mediated effects on retinal progenitor cell proliferation'''
]]
|}

-------------------------

===Stem Cells===

[http://www.advancedcell.com/patients/clinical-trial-information/ Advanced Cell Technology] is a biotechnology company which is currently running two clinical trials that utilise human embryonic stem cell derived retinal pigmented epithelial cells. These trials are examining the possibility of using these cells to treat stargardt's macular dystrophy and dry age-related macular degeneration.

Despite the discovery of human embryonic stem cells (hESCs) 13 years ago, these trials are the first to describe the subretinal transplantation of hESCs into humans. The participants in these trials were sufferers of Stargardt's macular dystrophy or dry age-related macular degeneration, which is the chief cause of blindness in the developed world.

The trials were relatively successful in the sense that the hESC-derived retinal pigment epithelium cells that were implanted integrated well into the existing tissue, and there were no signs of hyperproliferation, abnormal growth, or rejection. The authors hope that in future this technique will be applied to patients in the earlier stages of disease, preventing disease progression<ref><pubmed>22281388</pubmed></ref>.

-------------------

[[File:Bionic_eye.JPG|right|thumb|300px|Early prototype of the bionic eye.]]
===Bionic Eye===

[http://bionicvision.org.au/ Bionic Vision Australia] are the first organisation to implant a bionic eye. In 2012 a prototype made up of a retinal implant with 24 electrodes was implanted into 3 different patients with retinitis pigmentosa.

A camera is used to capture images which are transferred to an external data processing unit. From here the data is processed and transmitted via a wire to the implanted receiver, which in turn sends the signal to the retinal implant. The retinal implant is then able to stimulate the visual pathways in the brain.

Bionic Vision Australia hopes that in 2013, trials for a wide-view device that consists of 98 electrodes will be in progress. This prototype will be inserted into the suprachoroidal space in order to prevent mechanical damage to the retina. Trials for a more advanced high-acuity device with 1024 electrodes are planned for 2014. The electrode array contained in this device will be made of diamond to prevent irritation of surrounding tissues. These devices are expected to be suitable for patients with retinitis pigmentosa and age-related macular degeneration. The eventual goal will be to provide a completely wireless device which gives the patient high visual acuity.

----

===MIP/Aquaporin 0 Represents a Direct Transcriptional Target of PITX3 in the Developing Lens===

<pubmed>21698120</pubmed>

{| width=800px
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|PITX3 plays a siginificant role in the development of lens in vertebrates. If there is a deficiency is PITX3, it causes a range of problems in humans such as microphthalmia, Peter’s anomaly, or isolated cataracts. Mutation of PITX3 also causes degeneration of the lens in zebrafish and mice. It is therefore important to understand what factors may affect the decrease in PITX3, as a normal level of PITX3 is needed to maintain normal eye development. The authors wanted to investigate specific genes which are affected by PITX3. Previous research has shown that MIP and Aquaporin causes defects in the lens in both mice and humans. MIP and Aquaporin are targeted by PITX3, so their imbalance is interrelated in the cause of defects in the lens. Therefore it has been previously proven that PITX3 is needed for normal development of the lens. However, there has not been much information previously known regarding the exact effect that PITX3 has, or the specific genes it targets. Since MIP and Aquaporin is common genes found in humans, mice and zebrafish, the authors <ref name="PMID21698120"><pubmed>21698120</pubmed></ref> chose to study these genes to understand the pathway that PITX3 takes and its exact involvement in the development of the lens. Their results proved that deficiency in MIP and Aquaporin indeed affects normal development of the lens, and it is indeed related to deficiency in PITX3. However, there is still more research needed to understand PITX3 and the genes it interacts with, and their effect in ocular development.

|
[[File:Mip1-expression-in-pitx3.jpg|thumbnail|250px|'''Analysis of mip1 expression in pitx3-mo and control embryos via in situ hybridization and RT-PCR''']]
|}

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===Activation of c-Jun N-terminal kinase (JNK) during mitosis in retinal progenitor cells.===

<pubmed>22496813</pubmed>

{| width=800px
|-
| In the past, most studies about c-Jun N-terminal kinase (JNK) in the retina have been in relation to neurodegeneration. <ref name="PMID22496813"><pubmed>22496813</pubmed></ref> Therefore the authors in this article were interested in investigating the function of c-Jun N-terminal kinase in the retinal progenitor cells in neonatal rats. <ref name="PMID22496813"/> In the experiment, they took retinal tissue from newborn rats and fixed them, and subsequently examined them using confocal microscopy and fluorescence to discover c-Jun N-terminal kinase ‘phosphorylation by immunohistochemistry’. <ref name="PMID22496813"/> Mitotic cells in the retina were identified during the experiment. The results of their experiment revealed that c-Jun N-terminal kinase is phosphorylated in the developing retina of neonatal rats during the mitosis of progenitor cells. <ref name="PMID22496813"/> This shows that c-Jun N-terminal kinase can control the proliferation of progenitor cells in the developing retina. Their experiment also revealed that inhibiting c-Jun N-terminal kinase causes disruptions to the mitotic cell cycle by reducing the cell numbers in anaphase. <ref name="PMID22496813"/> However, inhibiting c-Jun N-terminal kinase did not change the cell numbers in metaphase or prophase. <ref name="PMID22496813"/>

|
[[File:JNK1.png|thumbnail|300px|'''"JNK is phosphorylated during mitosis of retinal progenitor cells."''']]
|}

----------------------------

===LRP5 is required for vascular development in deeper layers of the retina===

<pubmed>20652025</pubmed>

{| width=800px
|-
|
The lipoprotein receptor-related protein 5 (LRP5) has a significant function in the development of retinal vasculature.<ref name="PMID20652025"><pubmed>20652025</pubmed></ref> Research has shown that mutations of the LRP5 causes loss of function, due to incomplete development of retinal vessel network, in both humans and mice. The authors investigated how mutations occur in the LRP5, which leads to abnormal development of the retinal vasculature. They have studied retinal endothelial cells in mutant mice in their study. Their results showed that in retina with mutated LRP5, endothelial cells in the retinal vasculature primarily produced cell clusters in the inner-plexiform layer instead of migrating into deeper layers of the retina to form normal retinal vasculature. The authors also discovered that there was a decrease in Slc38a5, which is “a Müller cell-specific glutamine transporter”, in mice with mutated LRP5. Their results lead the authors to conclude that normal LRP5 is very important in the development of normal retinal vasculature due to their role in causing migration of retinal endothelial cells in the deeper layers of the retina. LRP5 is also important for retinal interneurons and Müller cells to function correctly.

|
[[File:Retina-cell-clusters.JPG|350px|thumbnail|'''Endothelial cells form thick clusters in the LRP5 mutant retina''']]
|}

-----------------

===Astrocyte-Derived Vascular Endothelial Growth Factor===

<pubmed>20686684</pubmed>

{| width=800px
|-
|
Vascular endothelial growth factor (VEGF) has an important role in normal development of retinal vasculature. <ref name="PMID20686684"><pubmed>20686684</pubmed></ref> In the process of vascularisation of the retina, the retinal astrocytes (both vascularised and not yet vascularised) expresses the vascular endothelial growth factor. <ref name="PMID20686684"/> This fact indicates that vascular endothelial growth factor that are derived from astrocytes of the retina plays an important role in vessel maturation and angiogenesis. <ref name="PMID20686684"/> Therefore the authors wanted to test the role of vascular endothelial growth factor that are derived from astrocytes to find further confirmation. ‘Cre-lox technology’ was used in the experiment to remove the vascular endothelial growth factor from mice retinal astrocytes in the developmental period. <ref name="PMID20686684"/> The results showed that removing vascular endothelial growth factor that are derived from astrocytes caused ‘the regression of smooth muscle cell-coated radial arteries and veins’ from the effects of hyperoxia. <ref name="PMID20686684"/> Hence, this result indicates that vascular endothelial growth factor plays an important role in stabilising blood vessels during the development of the retinal vasculature. <ref name="PMID20686684"/> It has been suggested that this finding may be of relevance to retinopathy in premature neonatal humans. <ref name="PMID20686684"/>

[[File:Astrocyte-vegf-deletion.JPG|250px|thumbnail|'''"Astrocyte specific deletion of VEGF." ''']]
|
[[File:Effect-of-vegf-on-retinal-vasculature.JPG|250px|thumbnail|'''"Effects of astrocyte-derived VEGF on retinal vascular development."''']]
[[File:Vegf-protects-vessels.JPG|250px|thumbnail|'''Astrocyte-derived VEGF protects vessels from hyperoxia. ''']]

|}

==Useful Links==

{{External Links}}

[http://www.youtube.com/watch?v=Xme8PA6xv-M Visualisation of eye development in the embryo]

[http://www.youtube.com/watch?v=wJE6pYwAMVU Brief Video on Embryonic development of the eyes]

[http://www.embryo.chronolab.com/sense.htm Embryonic Development of the eye]

[http://webvision.med.utah.edu/book/ Webvision free online textbook]

[http://www.ophthobook.com/chapters/ Free basic online book about the eyes]

[http://www.youtube.com/watch?v=deEjbVdnwyA&feature=related Anatomy of the Eyes- Video]

[http://www.vetmed.vt.edu/education/curriculum/vm8054/eye/EMBYEYE.HTM Simple eye embryology explanation]

[http://www.vetmed.vt.edu/education/curriculum/vm8054/eye/chambers.htm The chambers of the Eye]

[http://www.sciencedirect.com/science/journal/13509462 Progress in retinal and eye research journal]

[http://www.sumanasinc.com/webcontent/animations/content/visualpathways.html Animation showing the visual pathway]

[http://www.youtube.com/watch?v=f0JpsTgy6ck Video describing the layers of the retina]

[http://www.youtube.com/watch?v=Wm66gCid-kE&NR=1&feature=endscreen Video on visual processing in the retina]

[http://www.ncbi.nlm.nih.gov/books/NBK10024/ Development of the vertebrate eye]

[http://www.childrensvision.com/development.htm Easy-to-understand descriptions of the development of vision after birth]

[http://archive.org/details/atextbookembryo01heisgoog John Clement Heisler's historic textbook on Embryology (1907) ]

==Glossary==

'''Accommodation''' - changing the focal length of the lens in order to focus on an object.

'''Anterior chamber''' - Fluid-filled area located between the iris and cornea.

'''Choroid''' - The middle coat of the eye, located between the sclera and retina, which contains blood vessels that nourish the structures in the eye.

'''Ciliary body''' - Structure located behind the iris which secretes aqueous humour. It contains ciliary muscle, which is involved with changing the shape of the lens for accommodation.

'''Cornea'''- a transparent section in the anterior of the eye which acts as a window over the pupils, and is involved with refracting light as it enters the eye.

'''Downstream genes''' - genes that are activated by other "upstream genes".

'''Ectoderm''' - outermost layer of germ cells in an early embryo.

'''Endoderm''' - innermost layer of germ cells in an early embryo.

'''Extraocular muscles''' - Muscles that control the movement of the eyeball.

'''Glial cells''' - non-neuronal cells that provide structure and protection to neurons as well as producing myelin.

'''Inductive signaling''' - a process whereby the secretion of factors from one cell or tissue triggers a response in another.

'''Iris'''- A circular shaped muscle which controls the opening and contraction of the pupil.

'''Lens'''- A structure inside the eye which refracts light as it enters the eye for clear vision.

'''Lens vesicle''' - the cavity of invaginated ectoderm from the optic placode that will form the lens.

'''Macula''' - a highly pigmented, oval-shaped area located near the centre of the retina. Important for visual acuity.

'''Mesenchyme''' - undifferentiated, loose connective tissue.

'''Mesoderm''' - middle layer of germ cells in an early embryo.

'''Mesothelium''' - the epithelial layer of the mesoderm.

'''Myelinisation''' - development of a myelin sheath around a nerve fibre.

'''Neural crest''' - a portion of the ectoderm situated next to the neural tube.

'''Neural groove''' - a large invagination on the dorsal surface of the embryo which will close off and form the neural tube.

'''Neural tube''' - hollow structure that results from the folding of the neural plate and eventually forms the central nervous system.

'''Neuroblastic layer''' - a layer of immature cells that differentiate to form either glial cells or neurons. The retina has two of these (an inner and outer).

'''Neuroectoderm''' - portion of the ectoderm that develops to form the central and peripheral nervous systems.

'''Optic chiasm''' - the point at which the optic nerves meet and cross over.

'''Optic cup''' - the structure that is formed after the optic vesicle folds in upon itself. This will form the retina.

'''Optic globe''' - a term that refers to the optic cup, lens vesicle and surrounding mesenchyme collectively.

'''Optic Nerve''' - The nerve which carries visual information from the retina to the brain for processing.

'''Optic placode''' - area of thickened ectoderm that gives rise to the lens of the eye.

'''Optic stalk''' - a long, narrow cavity that will produce the optic nerve.

'''Optic vesicle''' - a cavity that buds off from the neural tube and gives rise to the optic cup.

'''Posterior chamber'''- Fluid-filled area located between the iris and lens.

'''Pupil'''- opening in the anterior part of the eye, which controls how much light enters the eye.

'''Retina''' - Light-Sensitive portion located towards the back of the internal surface of the eye, which contains photoreceptors (rods and cones) which detects visual information and transmits it to the brain through the optic nerve.

'''Sclera'''- white part of the external anterior surface of the eye, which envelopes the eyeball to give it support and protection of its internal contents.

'''Upstream genes''' - genes that activate one or more other "downstream genes".

'''Vascularise''' - to invade with blood vessels.

'''Vitreous Chamber'''- Area located between the lens and retina, which contains vitreous (a jelly like substance) whose function is to maintain the shape of the eye.

==Image Gallery==
<gallery>
Image:Eye_diagram_bandw.jpg‎ | Basic structure of the human eye.
Image:Eyediagramcolour1.JPG | Basic anatomy of the eye.
Image:Stage14 sem2b-limb.jpg | A Stage 14 embryo showing the location of an otic placode.
Image:Stage 13 image 060.jpg | A cross section showing the organisation of the developing brain, the optic vesicle and the lens (optic) placode.
Image:Formation of the optic vesicle 1.jpg | Early formation of the optic vesicle from the neural groove.
Image:Formation of the optic vesicle 2.jpg | The optic vesicle at a later stage, showing the optic stalk.
Image:Formation of the optic nerve and chiasm 1.jpg | A recognisable brain and eye structure in later development.
Image:Formation of the optic cup 1.jpg | Mechanism of optic cup formation.
Image:Formation of the optic cup 2.jpg | Layers of the optic cup in retina development.
Image:Formation of the retina 1.jpg | Cross-section of the primitive retina showing cell types and layers.
Image:Formation of the retina 2.jpg | Cross-section of a developed retina showing cell types and layers.
Image:Formation of the lens 1.jpg | The importance of the optic cup in lens differentiation.
Image:Formation of the lens 2.jpg | The lens placode separates from the ectoderm and migrates into the mesoderm forming the lens vesicle.
Image:Formation of the choroid and sclera 1.jpg | The choroid and sclera derives from mesenchyme surrounding the optic cup.
Image:Formation of the eyelid 1.jpg | Small grooves in the ectoderm of the head - the precursors to an eyelid.
Image:Formation of the eyelid 2.jpg | The eye at an advanced stage of embryonic development. Note however, that the eyelids remain fused until much later.
Image:Bionic_eye.JPG | An early prototype of the bionic eye.

</gallery>

==References==
<references/>

----

--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

----

{{2012Projects}}

2012 Group Project 1

2012-10-03T01:33:45Z

Z3254758: /* Bionic Eye */

[[File:Eye_collage_2.jpg|right|830px]]

=Vision Development=

==Introduction==

Eyes are an important sensory organ shared across many different species and allow organisms to gather useful visual information from their environment. The visual system uses light from the environment and processes this information in the brain for visual perception. The visual system is complex, and is made up of various structures that work together to form vision. Each of the structures in the eye have specific tasks which contribute to the visual system. Knowledge of how the eye develops extends as far back as Aristotle more than 2000 years ago, and current knowledge shows that most of the crucial events of eye development occur in the embryological stage. The eye is an interesting model for studying the development of tissues in organisms, as it consists of cells from several parts of the embryo including the head ectoderm, neural ectoderm and mesoderm. From its many origins the cells come together and differentiate to produce the complex organ that is the eye. During this period there are many examples of inductive signaling, as the tissues coordinate their development throughout this elegant process.

The main anatomical structures of the eye are as follows:
{|
|
* Cornea

* Sclera

* Choroid

* Iris

* Ciliary body

* Lens

* Anterior chamber

* Posterior chamber

* Retina

* Optic nerve

|[[File:eye_diagram_bandw.jpg|right|250px|thumb|Basic structure of the human eye.]]
|[[File:Eye-pupil-sclera-iris.jpg|thumbnail|200px|Illustration of the front of the eye, showing the sclera, iris and pupil.]]
|}
[[File:Eyediagramcolour1.JPG|550px]]

==Research History==

=== '''Brief Timeline of Historical Developments on the Eye and its Embryology''' ===

{| width=800px
|-bgcolor="CEDFF2"
| width=100px|'''Time'''
| width=700px|'''Discovery'''

|-bgcolor="F5FAFF"
| '''Ancient Egyptians'''
| First to document cataracts. It is described as being 'the white disease of the eye' or 'darkening of the pupil.' <ref>Edwards, D.D. (1996). Ophthalmology before Hippocrates. In the History of Ophthalmology, ed. D.M. Albert and D.D. Edwards. Cambridge, Mass.: Blackwell Science.</ref> The Egyptians had some knowledge of the eye, however it is not known how much of the anatomy of the eye was known in their era.

|-bgcolor="CEDFF2"
| '''535 BC'''

|
Ancient Greek philosopher Alcmaeon conducted dissection of humans for the first time in recorded history. This included dissection of the eye. However, not much is known about which anatomical features he discovered. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17.">Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17.</ref>

|-bgcolor="F5FAFF"
| '''384- 322 BC'''

| [[File:Aristotle-eye.jpg|200px|thumbnail|The eye according to Aristotle.<ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "> Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau </ref> Note the lens is missing, and there are three vessels drawn that was believed to transport fluid to and from the eye.<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
]]
Aristotle performed dissections of animal embryos.<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

When Aristotle described the embryo of a ten day old chicken, he wrote "The eyes about this time, if taken out, are larger than beans and black; if their skin is removed the fluid inside is white and cold, shining brightly in the light, but nothing solid." <ref name="Magnus, H. (1998). Ophthalmology of the ancients. In J. Hirschberg (Ed.), The History of Ophthalmology: The monographs, Vol. 4, Part 1 (F.C. Blodi, Trans.) Bonn: Wayenborgh.">Magnus, H. (1998). Ophthalmology of the ancients. In J. Hirschberg (Ed.), The History of Ophthalmology: The monographs, Vol. 4, Part 1 (F.C. Blodi, Trans.) Bonn: Wayenborgh.</ref>

Aristotle believed that the eyes started forming during early embryogenesis, however, he also believed that the eyes are the last organs to form completely, and he incorrectly thought that the eyes shrink in later embryonic development. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press.">Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press.</ref> .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"

| '''340 BC'''

| Lens is thought to have been discovered by Hippocrates, due to his descriptions of the contents of the internal eye There has been studies in chick development later on by followers of Hippocrates. They claimed that eyes were visible in early embryogenesis. .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
|-bgcolor="F5FAFF"
|'''25 BC - 50 AD'''

| [[File:Celsus-eye.jpg|150px|thumb|The eye according to Celsus. <ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "/>
Note the lens is placed in the centre of the eye, in the vitreous.<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> ]]

Aulus Cornelius Celsus wrote a Roman medical text called 'De Medicina' in which he wrote that the lens was the part of the eye from which vision originated. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.">Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.</ref> Celsus also incorrectly drew the lens in the center of the globe in his diagram of the eye. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

|-bgcolor="CEDFF2"
| '''23-79 AD '''
|
Pliny the Elder said that the eye is the last of the organs to develop in the womb <ref name="Magnus, H. (1998). Ophthalmology of the ancients. In J. Hirschberg (Ed.), The History of Ophthalmology: The monographs, Vol. 4, Part 1 (F.C. Blodi, Trans.) Bonn: Wayenborgh."/>
|-bgcolor="F5FAFF"
| '''98-117 AD'''

| [[File:Rufus-eye.jpg|150px|thumb|The eye according to Rufus of Ephesus. <ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "/>
Note the lens is placed in the correct position, behind the iris of the eye <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> ]]

Rufus of Ephesus identified the lens as being located in the anterior part of the eye, close to the pupil. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

His diagram illustrates that he knew the correct position of the lens as being directly behind the iris, in the anterior part of the eye, and not in the centre as was previously depicted by others before him.

|-bgcolor="CEDFF2"
| '''130-200 AD'''

| [[File:Galen-eye1.jpg|150px|thumb|The eye according to Galen. <ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "/> ]]

Claudius Galen practised medicine in Rome. He wrote:

"1. Within the eye the principal orgran of sensation is the crystalline lens.

2. The sensation potential comes from the brain and is conducted via the optic nerves.

3. All other parts of the eyeball are supporting structures." <ref> Hirschberge, J. (1982). Antiquity, Vol. X in the History of Ophthalmology (F.C. Blodi, Trans.) Bonn: Wayenborgh. pp. 280 </ref>

Galen thought that the lens was produced from the vitreous. He also believed that the retina’s function was to give nourishment to the lens and vitreous, and to carry visual information to the brain from the lens. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

|-bgcolor="F5FAFF"

| '''1514-1564'''

| Andreas Vesalius published his anatomy book "De Humani Corporis Fabrica in 1543. He had the misconception that the lens was located in the centre of the eyeball. .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> He also wrote that the lens functioned "like a convex lens made of glass" <ref name="Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.">Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.</ref> pp. 48
|-bgcolor="CEDFF2"
| '''1535-1606'''

| Georg Bartisch correctly drew a diagram of the lens placed behind the iris in his book 'Ophthalmodouleia: das ist Augendienst'. <ref name="Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>
|-bgcolor="F5FAFF"

| '''1537-1619'''

| Fallopio Hieronymus Fabricius ab Aquapendente studied anatomy and embryology. He studied chicken embryos, and thought that chalazae (which comes from egg white) gives rise to the eyes. He also drew the lens directly behind the iris in a diagram in is book 'Tractatus de Oculo Visuque Organo. <ref name="Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

|-bgcolor="CEDFF2"
| '''1583'''

| Felix Platter published his book 'De corporis Humani Structura et Usu, after he performed dissections of human bodies. He believed that the retina is the primary visual organ in the eye. .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="F5FAFF"
| '''1619'''
| Scheiner is given credit to be the first person to correctly draw the diagram of the anatomy of the eye. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
|-bgcolor="CEDFF2"
| '''1672'''
| Marcello Malpighi described the embryonic development of the chicken. He drew many detailed diagrams of the chick eye. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1665'''
| Nicolaus Steno identified the choroid fissure in his study of a developing embryo of a chicken. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="CEDFF2"
| '''1754'''

| Albrecht von Haller studied the embryology of the eye. With help from his student Johann Gottfried Zinn, he contributed to the understanding of the development of the ciliary body, ciliary zonule, and their relationship with the lens and vitreous. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1817'''

| Christian Pander discovered the three embryonic germ layers, which he wrote about in his book. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/> Pander was the first to think of 'the optic vesicles as lateral evaginations' of the 'prosencephalon'; however, he was incorrect about the details regarding how 'the eye develops from these evaginations'. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="CEDFF2"
| '''1828-1837'''

| Karl Ernst von Baer studied embryology. He discovered that the optic vesicles were 'outgrowths of the embryonic forebrain' <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> which he believed was caused by pressure from fluids in the central nervous system. Von Baer also believed that the optic vesicle opens to form the pupil, and that fluid in the optic vesicle coagulates to form the vitreous body and lens. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1830'''

| Emil Huschke discovered that the lens forms from the invagination of the surface ectoderm. He concluded that the lens hence does not form ‘from the fluid of the optic vesicle’ <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> as previously thought.
|-bgcolor="CEDFF2"
| '''1832'''

| Emil Huschke wrote in his manuscript ‘Ueber die erste Entwinkenlung des Auges und die damit zusammenhängende Cyklopie’ that the lens capsule forms from the outer surface ectoderm, which detaches and moves back inward, which is later enclosed again by several membranes, such as by the cornea. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

Huschke also described how the optic cup and choroid fissure forms. He discovered that the optic vesicles are produced from the two-layered optic cup. However, he incorrectly described the destiny of the ‘individual optic cup layers’. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

|-bgcolor="F5FAFF"
| '''1838'''
| Matthias Jakob Schleiden and Theodor Schwann formulated the ‘cell theory’: “All living things are formed from cells, the cell is the smallest unit of life, and cells arise from pre-existing cells.” <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
|-bgcolor="CEDFF2"
| '''1839'''

| Theodor Schwann contributed a better understanding of the development of the lens through studying the foetus of a pig, which he wrote about in his book ‘Mikroskopische Untersuchungen Über Die Uebereinstimmung in Der Struktur Und Dem Wachsthum Der Thiere Und Pflanzen’. He wrote that the lens is made of ‘concentric layers’ of fibres which proceeds from an anterior to posterior direction. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1842'''
| Robert Remak gave the current names to the three embryonic germ layers: ectoderm, mesoderm and endoderm. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"
| '''1843'''
| Wilhelm Werneck published his book ‘Beiträge zur Gewebelehre des Kristallkörpers’. He wrote that the contents inside of the lens is not made of fluids, as was previously believed. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/> Werneck also discovered that the fibers of the lens continues to grow from the outside to the centre during embryogenesis. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

|-bgcolor="F5FAFF"
| '''1855'''

| Robert Remak wrote his book ‘Untersuchungen über die Entwickelung der Wirbelthiere’. He wrote about what he discovered in his studies of the development of the eye in the embryos of chickens, frogs, and rabbits. He wrote very descriptively about the embryology of lens formation, amongst other topics. He discovered that the ectoderm gives rise to the lens placode. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

|-bgcolor="CEDFF2"
| '''1858'''
| Henry Gray published his book 'Anatomy, Descriptive and Surgical'. He had also previously studied the embryonic development of the optic nerve and retina of chickens.
|-bgcolor="F5FAFF"
| '''1877'''
| Paul Leonhard Kessler wrote about the embryonic development of the lens in mice in his book ‘Zur Entwickelung des Auges der Wirbelthiere. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"
| '''1891'''
| Vincenzo Colucci studied newts and discovered their ability to regenerate the lens.<ref> Tsonis, P. A. (2001). Regeneration of the Vertebrate Lens and Other Eye Structures. eLS. (Online Publication). DOI: 10.1038/npg.els.0001102 </ref>
|-bgcolor="F5FAFF"
| '''1892'''
| Dr. Oscar Hertwig published his book ‘Text-Book of the Embryology of Man and Mammals. <ref> Hertwig, O. Text-book of the embryology of man and mammals. S. Sonnenschein 1901. (Translated from the 3d German ed. by Edward L. Mark.) </ref> It contains a very detailed description of the development of the eye, according to the findings at that time. [http://embryology.med.unsw.edu.au/embryology/index.php?title=Book_-_Text-Book_of_the_Embryology_of_Man_and_Mammals_16-2#The_Development_of_the_Eye]
|-bgcolor="CEDFF2"
| '''1895'''
| Gustav Wolff also independently studied newts and discovered their ability to regenerate the lens. .<ref> Tsonis, P. A. (2001). Regeneration of the Vertebrate Lens and Other Eye Structures. eLS. (Online Publication). DOI: 10.1038/npg.els.0001102 </ref>

|-bgcolor="F5FAFF"

| '''1900'''
| Carl Rabl published his book ‘Uber den Bau und die Entwicklung der Linse’. He wrote about the development of the lens in mammals, fish, birds, reptiles, and amphibians. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"
| '''1901'''
| Hans Spemann published his findings from his experimental studies about the formation of the lens in the frog. He found that the optic cup needed to be in contact with the ectoderm for normal development of the eye. <ref> Spemann, H. (1901). Über Correlationen in der Entwicklung des Auges. Verhand. Anat. Ges. 15: 61-79. </ref> <ref> Saha, M. (1991). Spemann seen through a lens. In Gilbert, S. F. (ed.). A Conceptual History of Modern Embryology. Plenum Press, NY. pp. 91-108.</ref>
|-bgcolor="F5FAFF"
| '''1906'''
| Brown ‘s book “The Embryology Anatomy and Histology of the Eye” was published. It contained detailed descriptions of the embryonic development of the eye according to the knowledge current at that time, mainly based on observations from embryos of rabbits and chickens. <ref> Brown, E.J. (1906). The Embryology Anatomy and Histology of the Eye. Chicago: Hazlitt & Walker. 1906 </ref>

|-bgcolor="CEDFF2"
| '''1907'''

| John Clement Heisler published his book ‘A Text-book of embryology’. It contains a chapter detailing the embryonic development of the eye, according to the knowledge current at that time. The book’s copyright has expired, so it can be viewed free online: [http://archive.org/details/atextbookembryo01heisgoog]

Julius Kollman also published his book 'Atlas of the Development of Man'. It contained very detailed description and illustrations showing the embryonic development of the human according to the knowledge current at that time. His illustrations were reused by many others after his time and built upon for further refined understanding of the embryology of the human.

Here are examples of Julius Kollman's excellent illustrations showing eye development in various stages:

'''Formation of Primary Optic Vesicle:'''
<gallery>
File:Kollmann691.jpg|The blue part at the bottom is the endoderm. The pink middle layer is the mesoderm. The top yellow layer is the ectoderm. The fold labelled as 'augenfeld' is the place where the optic vesicle will form.
File:Kollmann692.jpg|The eye area (augenfeld) is a bowl shaped bulge still located on the side walls.
File:Kollmann693.jpg| The neural tube is shown after removal of all of the ectoderm and ventral organs, such as heart, gut tube, etc. The primary optic vesicle forms a slightly flattened hollow protrusion on the forebrain.
File:Kollmann694.jpg|The lateral surface of the primary optic vesicle is slightly depressed, showing the first sign of the emergence of the secondary optic vesicle
</gallery>

'''Development of Lens:'''

<gallery>
File:Kollmann695.jpg|The bulging lateral wall of the primary optic vesicle is covered by a fairly well demarcated lens plate, a direct continuation of the ectoderm. Between the optic vesicle and the lens pit are some flattened spindle-shaped cells. In the adjoining mesoderm are cross-sections of capillaries.
File:Kollmann697.jpg|The lens still hangs together with the ectoderm. The primary eye vesicle is indented with respect to the lens. Between the lens and the lateral plate of the optic vesicle is a narrow space, which allows area to further develop later.
File:Kollmann698.jpg|4th Week of development. The internal organisation shows the secondary optic vesicle. A: The rear wall of lens is noticeable and is enveloped by mesoderm. B: The edges of the lens pit is already grown and the lens vesicles are formed, which is still related to the remaining ectoderm.
File:Kollmann699.jpg|The lens has now cut off from the ectoderm, but is still very superficial. Between it and the lateral lamina of the optic cup, there is a considerable space. The eye stalk has become longer and is enclosed together with the optic cup and lens of the mesoderm. The cornea, sclera and choroid make gradual development.
</gallery>

|-bgcolor="F5FAFF"

| '''1921'''
| Bailey and Miller published their textbook “Text-Book of Embryology “. <ref> Bailey, F.R. and Miller, A.M. (1921). Text-Book of Embryology. New York: William Wood and Co. (Note- This book is only at an early edited stage)</ref> It contains detailed description of the development of the embryonic eye according to the knowledge current at that time. [http://embryology.med.unsw.edu.au/embryology/index.php?title=Book_-_Text-Book_of_Embryology_18]

|-bgcolor="CEDFF2"
| '''1925'''

| Mann published his research article, in which he gives a detailed account of the development of the human iris. He divided the development of the iris into four stages: weeks 4-7 (before the ectodermal iris forms or before the anterior chamber forms); weeks 7-11 (anterior chamber appears, and mesodermal iris forms); weeks 11-12 (ectodermal iris forms); 3-8 months (muscles of the pupil forms from ectodermal iris, and the central portion of the mesodermal iris atrophies to make the pupil clear). <ref name="PMID18168466"><pubmed>18168466</pubmed></ref>
O Leser also published an article detailing the development of extraocular muscles in mammals he studied. <ref name="PMID18168498"><pubmed>18168498</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1939'''
| Holtfreter <ref> Holtfreter, J. (1939). Gewebeaffinitat, ein Mittel der embryonalen
Formbildung. Arch. Exp. Zellforsch. 23, 169-209. </ref> studied amphibians and observed that that the development of the eye stops at the ‘optic vesicle stage’ if there is no contact ‘with the epidermis and neural crest driven mesenchyme’. <ref name=”PMID11023863”><pubmed>11023863</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1955'''
| Barber published his book ‘Embryology of the human eye’. <ref> Barber AN: Embryology of the human eye. St. Louis. CV Mosby 1955</ref> In contains detailed descriptions of the embryological development of the human eye according to the knowledge current at that time. It contains many photographs of the eye at different stages of development.

|-bgcolor="F5FAFF"
| '''1957'''
| Coulombre studied a chicken embryo to find the role of intraocular pressure in the development of the chick’s eye, especially in regards to its control of the size of the eye structures. <ref name="PMID13469954"><pubmed>13469954</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1958'''
| Coulombre studied the development of the cornea and how it develops its transparency. <ref name="PMID13563560"><pubmed>13563560</pubmed></ref> He also studied the development of corneal curvature. <ref name="PMID 13519969"><pubmed> 13519969</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1962'''
| Coulombre studied the development of the conjunctival papillae and scleral ossicles. <ref name="PMID 14023393"><pubmed> 14023393</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1963'''
| Coulombre studied the development of lens fibers and their orientation. <ref name="PMID14077035"><pubmed>14077035</pubmed></ref> He also studied the development of pigmented epithelium. <ref name="PMID14023394"><pubmed>14023394</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1964'''

| Coulombre further studied the development of the lens to determine the role of the lens in eye growth. <ref name="PMID14189921"><pubmed>14189921</pubmed></ref> He also studied the role of thyroid in the development of the cornea and the development of corneal transparency. <ref name="PMID14211912"><pubmed>14211912</pubmed></ref> Mann also published his work called ‘The development of the human eye’, which contains detailed description of the embryonic development of the eye according to current knowledge at that time. <ref> Mann I. The development of the human eye. New York: Grune and Stratton 1964</ref>

|-bgcolor="CEDFF2"
| '''1965'''
| Coulombre published his findings regarding the regeneration of the neural retina from pigmented epithelium in the embryo of chickens. <ref name="PMID5833111"><pubmed>5833111</pubmed></ref> Smelser also published his findings on the embryological development and morphology of the lens. <ref name="PMID14340157"><pubmed>14340157</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1966'''

| Formation of the face and orbit occurs from the differentiation of neural crest cells. <ref name="PMID5969670"><pubmed>5969670</pubmed></ref> O’Rahilly also published findings of the development of the eye in the early stages of human embryos. <ref> O'Rahilly, R. 1966 The early development of the eye in staged human embryos. Contr. Embry. Carnegie Inst., Wash., 38: 1–42</ref>

|-bgcolor="CEDFF2"
| '''1968'''
| Findings of the postnatal development of the retina of rats was published. <ref name="PMID5640327"><pubmed>5640327</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1969'''

| Mann again published his work called ‘The development of the human eye’. He stated that that the lens in humans forms completely from the ectoderm. <ref name=”Mann I. The Development of the Human Eye. New York, USA: Grune & Stratton, Inc; 1969”> Mann I. The Development of the Human Eye. New York, USA: Grune & Stratton, Inc; 1969</ref> Coulombre also studied the development of the lens, and took note of its size, shape and orientation throughout its developmental stages. <ref name="PMID 5772716"><pubmed> 5772716</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1970'''
| Coulombre again further studied the regeneration of the neural retina from pigmented epithelium of embryos of chickens. <ref name="PMID 5472476"><pubmed> 5472476</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1971'''

| Coulombre further studied the development of the lens. This time he focused on analysing the histological mechanisms in the reconstitution of the lens from implanted lens epithelium. <ref name="PMID 4925671"><pubmed> 4925671</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1973'''
| A research article was published, detailing the embryonic development of the retina of humans. <ref name="PMID 6650859"><pubmed> 6650859</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1976'''

| Geeraets published his observations of the closure of the embryonic optic fissure in golden hamsters, using the electron microscope. <ref name="PMID 1266776"><pubmed> 1266776</pubmed></ref> Kornneef also published an article based on his studies of the development of connective tissue in the human orbit. <ref name="PMID 1020699"><pubmed> 1020699</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1981'''
| A research article was published detailing how myelin forms in the optic nerve of humans. <ref name="PMID 7224936"><pubmed> 7224936</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1983'''
| O’Rahilly’s further research developments was published, reporting the timing and sequence of events in the development of the embryonic human eye. <ref name="PMID 6650859"><pubmed> 6650859</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1990'''

| Van Driell et al. <ref>Driell, D. Van; Provis, J.M.; Billson, F.A.: Early differentiation of ganglion, amacrine, bipolar and Muller cells in the developing fovea of the human retina. J. Comp. Neurol. 291: 203-219.</ref> studied the manner in which amacrine, bipolar, retinal ganglion cells, and Muller cells differentiate in the developing fovea of the retina of a 15-week old human foetus. <ref name="PMID1628748"><pubmed>1628748</pubmed></ref> Tripathy also published an article providing evidence that the lacrimal glands in humans originates from the neuroectoderm. <ref name="PMID2406219"><pubmed>2406219</pubmed></ref>

|}

==Development, Structure and Function of Ocular Components==

The eye itself is formed from several components; notably the optic placode of the head ectoderm, the optic vesicle from the neural tube, and mesenchyme from the mesoderm and neural crest cells. The optic placode contributes the lens to the eye, the optic vesicle gives rise to layers of the retina, while the mesenchyme will produce the ciliary body, iris, choroid and sclera.<ref>http://www.vetmed.vt.edu/education/curriculum/vm8054/eye/EMBYEYE.HTM</ref> Cells from the neural tube will also produce the optic nerve, which receives nerve impulses from the retina of the eye. Eyes initially form as laterally paired structures and migrate medially in the human embryo. In other animals such as birds and lizards, the eyes do not migrate and develop laterally on the head. The optic placodes become prominent on the surface of the embryo at approximately Stage 14 of development.

[[File:Stage14 sem2b-limb.jpg|200px|thumb|left|A Stage 14 embryo showing the location of an otic placode.<ref name="http://embryology.med.unsw.edu.au/embryology/index.php?title=ANAT2341_Lab_6_-_Early_Embryo">http://embryology.med.unsw.edu.au/embryology/index.php?title=ANAT2341_Lab_6_-_Early_Embryo</ref>]] [[File:Stage 13 image 060.jpg|400px|thumb|center|A cross section showing the organisation of the developing brain, the optic vesicle and the lens (optic) placode.<ref name="http://embryology.med.unsw.edu.au/embryology/index.php?title=ANAT2341_Lab_6_-_Early_Embryo"/>]]

===Optic Nerve===

The optic nerve consists of nerve fibres that transmit information from the retinal photoreceptor cells to the brain. The optic nerve is formed from the optic stalk, which develops as the optic vesicle migrates from its origin in the neural tube to its destination - the surface ectoderm - where it will fuse with the optic placode (also known as the lens placode, which will contribute the lens to the eye).<ref name="PMID11687490"><pubmed>11687490</pubmed></ref>

[[File:Formation of the optic vesicle 1.jpg|400px|thumb|left|Fig. 1: Early formation of the optic vesicle from the neural groove.]] [[File:Formation of the optic vesicle 2.jpg|400px|thumb|center|Fig. 2: The optic vesicle at a later stage, showing the optic stalk.]]

As can be seen in Figure 1 above, the optic vesicle forms from the neural tube. However, note that the neural tube has not yet closed, and is still the neural groove at this point. Figure 2 then shows the optic vesicle at slightly later stage in the same simplified cross-section of the embryo, as it migrates from the neural tube to the surface ectoderm. Note the presence of the optic stalk which links the optic vesicle to the neural tube. Later in development, this primitive structure will become the optic nerve, which will link the eye to the brain.

The nerve fibres themselves will initially originate from the retinal ganglion cells in the eye during week 6.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008">Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008</ref> After two weeks, these fibers will have grown along the inner wall of the optic stalk and have reached the brain. They grow both in length and width, with the nerve fibres filling the hollow optic stalk to form the solid optic nerve. More than one million nerve fibers will eventually make up the optic nerve, along with glial cells which arise from the inner wall of the optic stalk itself.<ref><pubmed>1451666</pubmed></ref> Myelinisation of the optic nerve begins much later in development at around 7 months, beginning at the optic chiasm and moving towards the eye.<ref><pubmed>7224936</pubmed></ref> The optic chiasm forms just before the nerves reach the brain, and is where half the nerve fibres from each eye will cross over to the opposite side of the brain. This is demonstrated in Figure 3. Note the crossing over of the optic nerves just before they enter the brain, at the optic chiasm. This organisation is now much more familiar, with the eyes near the ectoderm and the optic nerve leading through the mesoderm to the brain buried deep in the embryo.

[[File:Formation of the optic nerve and chiasm 1.jpg|400px|thumb|center|Fig. 3: A recognisable brain and eye structure in later development.]]

===Retina===

The retinal component of the eye is formed when the optic vesicle folds in upon itself, forming the optic cup (see Figure 4). In doing so it creates two layers - an inner wall and an outer wall of the optic cup (Figure 5). These two layers of the optic cup will give rise to the two layers of the retina - the inner neural retina, and the outer pigmented epithelium.<ref name="PMID11687490"/> Note the existence of the space between the two layers of the retina. This is known as the intraretinal space and disappears by the 7th week of development, however the two layers never completely fuse and can become separated as a result of physical trauma to the head - leading to a detached retina and loss of vision.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/>

The inner wall of the optic cup, which will give rise to the neural retina, consists of a layer of pseudostratified cells (see Figure 6) that later differentiate into rod, cone, bipolar, ganglion, horizontal, amacrine and glial cells of the retina (Figure 7).<ref name="PMID18168748"><pubmed>18168748</pubmed></ref> The outer wall of the optic cup consists of a layer of cuboidal cells that contain melanin - the light absorbing pigment. The function of this layer is to absorb light and prevent internal reflection of light within the eye, which would impair our ability to form distinct images. Interestingly, in some animals such as cats, this layer actually reflects light intentionally to increase the amount of light available to the eye in low-light conditions. This is why cats seem to have eyes that glow in the dark.<ref>http://dialspace.dial.pipex.com/agarman/bco/fact4.htm</ref>

[[File:Formation of the optic cup 1.jpg|400px|thumb|left|Fig. 4: Mechanism of optic cup formation.]] [[File:Formation of the optic cup 2.jpg|400px|thumb|center|Fig. 5: Layers of the optic cup in retina development.]]

The inner wall itself is divided into two components - the inner neuroblastic layer and the outer neuroblastic layer (see Figure 6). The outer neuroblastic layer forms the rod and cone cells while the inner neuroblastic layer forms the remaining cell types found in the retina - the bipolar, ganglion, horizontal, amacrine and glial cells (Figure 7).<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/> The organisation of the retina is interesting in that incoming light passes through several layers of these neural retina cells before it is detected by rod and cone cells at the back of the retina, and then nerve signals are passed back through the layers of neural retina cells that the light just passed through moments before - a seemingly strange design that the eye does not share with man-made light-capturing devices such as a camera (imagine putting the wires in front of the image sensor!).

Differentiation of the neuroblastic layers into neural retina cells occurs in a pattern both within the layers and across the retina. Cells differentiate from the inner neuroblastic layer to the outer neuroblastic layer, and differentiate from the central retina to the peripheral retina.<ref name="PMID18168748"/> The macula is first identifiable in week 22 when ganglion cells start to form multiple rows, and the primitive fovea begins to form at approximately the same time as a depression in the macula.<ref><pubmed>6462623</pubmed></ref> It is not until 15-45 months after birth that this area becomes exclusively populated by cone cells and becomes the fovea centralis - the area of the retina with the highest visual acuity.

[[File:Formation of the retina 1.jpg|400px|thumb|left|Fig. 6: Cross-section of the primitive retina showing cell types and layers.]] [[File:Formation of the retina 2.jpg|400px|thumb|center|Fig. 7:Cross-section of a developed retina showing cell types and layers.]]

===Ciliary Body===

The ciliary body consists of ciliary processes and three portions of fibres that constitute the ciliary muscles. It functions to maintain normal eye physiology as well as playing a direct role in accommodation.

During development, the ciliary processes form slightly posterior to the iris, developing from part of the anterior rim of the optic cup. It is thought that the folded structure of the ciliary processes is brought about by intraocular pressure and specific signalling pathways.<ref name="PMID16959249"><pubmed>16959249</pubmed></ref> While the ciliary muscles and the endothelial cells of the ciliary blood vessels are chiefly formed by mesenchymal cells<ref><pubmed>16249499</pubmed></ref>, the neural crest and neuroectoderm also contribute to their development.<ref><pubmed>12127103</pubmed></ref> The normal development of the ciliary body is dependent on the correct expression of bone morphogenetic protein (BMP)-4, which is a member of the transforming growth factor-β superfamily.<ref><pubmed>1222340</pubmed></ref> Napier and Kidson (2007) summarised numerous genes that have been associated with ciliary body development, however their direct roles have not been well documented.<ref name="PMID16959249"/>

===Iris===

The iris is a thin layer that develops at the end of the third month of development and is derived from the anterior rim of the optic cup. The stroma of the iris develops from cells of neural crest cell origin.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/> The muscles that are responsible for the dilation and constriction of the pupil (dilator pupillae and sphincter pupillae muscles) form from the neuroectoderm of the optic cup. These cells are initially epithelial cells that then transform into smooth muscle cells. <ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"></ref>. The invagination of the optic vesicle which creates the optic cup, also causes the formation of the optic cup lip. This is the region of the where the epithelium doubles back, separating the outer pigmented layer and the inner nonpigmented layer. This is the edge of the iris that borders on the pupil<ref><pubmed> Retinal and anterior eye compartments derive from a common progenitor pool in the avian optic cup</pubmed></ref>.

The final colour of the iris is not evident until the postnatal period. It is determined by a number of genes including IRF4, SLC24A4 and MATP<ref><pubmed>19710684</pubmed></ref>. Other features such as crypt frequency, furrow contractions, presence of peripupillary pigmented ring, and number of nevi also become evident during development<ref><pubmed>21835309</pubmed></ref>. Mutations in Pax6 have been shown to cause partial or complete loss of the iris <ref><pubmed>12386935</pubmed></ref>.

===Cornea===

The cornea is the transparent, avascular, most anterior portion of the eye. It is responsible for conducting light into the eye and focusing it on to the retina, as well as maintaining the rigidity of the eyeball. It consists of 5 layers- the epithelium, Bowman’s layer, stroma, Descemet’s membrane and the endothelium.

The epithelium and endothelium of the cornea first appear during the 5th week of gestation. The epithelium of the external surface of the cornea is derived from surface ectoderm, while the mesenchyme is derived from the mesoderm<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"/>. The endothelium is a two-cell cuboidal layer which is made up of differentiated neural crest cells that were initially from the optic cup. By week 8 the endothelial cells begin to secrete a basement membrance which later forms Descemet’s membrane<ref><pubmed>6511224</pubmed></ref>. At approximately 16 weeks gestation the Bowman’s membrane begins to form from the thickening of the stroma that is located under the corneal epithelium<ref>Riordan-Eva P, Whitcher JP. Vaughn and Asbury's General Ophthalmology, Lange Medical Books/McGraw Hill. 2004:25–27</ref>. During the third month glycosaminoglycans secreted by fibroblasts form the ground substance of the cornea, with collagen fibrils and keratan sulphate also appearing around this time. Shortly after this tight junctions form between the endothelial cells<ref><pubmed>19481138</pubmed></ref>. Fibroblast growth factor causes the epithelial cells to proliferate<ref><pubmed>20105280</pubmed></ref>.

Towards the end of the gestational period the cornea becomes larger due to the production of aqueous humor<ref>Yanoff M, Duker JS. Ophthalmology. Mosby; St. Louis, MO: 2004</ref>. The final transparent structure develops because hyaluronidase removes hyaluronic acid, thyroxine causes dehydration of the stroma, and the entire structure becomes avascular<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/>. Numerous genes have been implicated in the development of the cornea, these include, but are not limited to, PAX6, PITX2, FOXC1, MAF, TMEM114, SOX2, OTX2 and BMP4<ref><pubmed>18637741</pubmed></ref>. Pax6 and Pax6(5a) isoforms are essential for the normal development of the eye. Over or under expression can both lead to major structural abnormalities<ref><pubmed>18386822</pubmed></ref>.

===Lens===

The lens has its origin from the optic placode, which develops on the ectodermic surface of the embryo and migrates both medially and inwards into the embryo. The lens allows accommodation of the eye, and adjusts its thickness in order to focus on near or far objects. The study of lens development was one of the first to highlight the importance of inductive signaling in development, with Spemann's pioneering work at the start of the 20th century, finding that the absence of retinal development resulted in the absence of lens formation.<ref name="PMID11687490"/> Indeed, it has been consistently shown that the interaction of the migrating optic vesicle with the surface ectoderm of the head is vital in producing differentiation of the lens.<ref name="PMID15558475"><pubmed>15558475</pubmed></ref> The mechanism of interaction is complex but basically involves upstream genes switching on downstream genes, with the genes eventually producing specialised proteins which constitute the lens. The whole process starts with the signaling molecules from the optic cup initiating a thickening of the surface ectoderm of the head (Figure 8). It is thought that this region of specific ectoderm is responsive to the signaling molecules, as lens formation is incomplete or absent when ectoderm from the lateral portion of the embryo (i.e. non-head ectoderm) is exposed to the same inductive signaling processes.<ref name="PMID9216064"><pubmed>9216064</pubmed></ref> Pax6 has been shown to be one of the major genes required for differentiation of the lens, which in turn switches on transcriptional genes such as Sox 1, 2 and 3 among others - producing water-soluble proteins called crystallins - responsible for giving the lens its transparency and refractive properties.<ref name="PMID9609835"><pubmed>9609835</pubmed></ref>

[[File:Formation of the lens 1.jpg|400px|thumb|left|Fig. 8: The importance of the optic cup in lens differentiation.]] [[File:Formation of the lens 2.jpg|400px|thumb|center|Fig. 9: The lens placode separates from the ectoderm and migrates into the mesoderm forming the lens vesicle.]]

The lens placode invaginates from the head ectoderm and migrates into the mesoderm (Figure 9). Once this structure (now known as the lens vesicle) is in place opposite the optic cup, the combined structure is referred to as the optic globe and resembles a recognisable eye structure. The lens continues to differentiate further, as mentioned above, through the formation of crystallin proteins, which give the lens its unique properties and allows for the fine control over the degree of refraction that takes place.

===Aqueous Chambers===

There are both anterior and posterior aqueous chambers of the eye which contain aqueous humour. A space develops in the mesenchyme situated between the lens and cornea to form the anterior aqueous chamber. The mesenchyme located superficially to this chamber forms the mesothelium as well as the transparent portion of the cornea.

The posterior chamber develops from a similar space in the mesenchyme, however it is located between the iris and the lens. The anterior and posterior chambers are able to communicate with one another once the papillary membrane vanishes and the pupil is formed. This channel is known as the scleral venous sinus.<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011">Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011</ref>

Contained within the aqueous chambers is aqueous humor. The production of aqueous humor is dependant on the development of the ciliary body. It is produced in the ciliary processes and it’s production is a metabolic process driven by the delivery of oxygen and the removal of wastes via the ciliary circulation<ref><pubmed>20801226</pubmed></ref>.

===Choroid and Sclera===

The choroid and sclera are adjacent layers that surround the eye and act to vascularise and protect the eye respectively. They are formed from neural crest and mesoderm-derived mesenchyme which condenses around the optic cup and lens vesicle between weeks 5 and 7 of development to form a primitive eyeball structure known as the optic globe.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/> Blood vessels first start to appear in the choroid layer at approximately week 15, and arteries and veins can be distinguished by week 23.<ref>Development of the Choroid and Related Structures, K. Sellheyer, Eye (1990) 4, 255-261</ref> Inductive processes are thought to play a vital role during formation of the choroid and sclera; with the retinal pigmented epithelium inducing differentiation of the surrounding mesenchyme while at the same time the neural crest-derived mesenchyme contributing components to the retinal pigmented epithelium such as melanocytes.<ref name="PMID1628748"/> In addition to having functional roles themselves, the primitive choroid and sclera also contribute components to the developing ciliary body and cornea (Figure 10). In the adult eye, the choroid is continuous with the ciliary body and the sclera with the cornea.

[[File:Formation of the choroid and sclera 1.jpg|400px|thumb|center|Fig. 10: The choroid and sclera derives from mesenchyme surrounding the optic cup.]]

===Eyelids===

The eyelids are ectodermal and mesodermal in origin and are an extension of the skin which covers and protects the eye. The surface ectoderm gives rise to the conjunctiva, skin epithelium, hair follicles, cilia, Zeis glands, glands of Moll, and meibomian glands. <ref name=" Cook CS, Ozanics V, Jakobiec FA. (1994) Prenatal development of the eye and its adnexa. In Tasman W, Jaeger EA, editors: Duane’s foundations of clinical ophthalmology, vol 1, Philadelphia, 1994, Lippincott. "> Cook CS, Ozanics V, Jakobiec FA. (1994) Prenatal development of the eye and its adnexa. In Tasman W, Jaeger EA, editors: Duane’s foundations of clinical ophthalmology, vol 1, Philadelphia, 1994, Lippincott. </ref> The mesenchyme gives rise to the tarsal plates, levator muscles, orbicularis muscles, and tarsal muscle of Muller. <ref name=" Cook CS, Ozanics V, Jakobiec FA. (1994) Prenatal development of the eye and its adnexa. In Tasman W, Jaeger EA, editors: Duane’s foundations of clinical ophthalmology, vol 1, Philadelphia, 1994, Lippincott. "/> Eyelid formation can be first noted during week 5 when small grooves develop in the surface ectoderm (Figure 11).<ref><pubmed>7364662</pubmed></ref> These small grooves deepen and extend into the mesoderm and the primitive eyelid structures grow towards one another, eventually fusing together during week 8.<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"/> It is not until week 26-28 that the eyelids will separate again. The anterior surface of the eyelid becomes covered by two layers of epithelium; this forms the epidermis of the eyelids. <ref name="Kikkawa DO, Lucarelli MJ, Shovlin JP, et al: Ophthalmic facial anatomy and physiology. In Kaufman PL, Alm A, editors: Adler’s physiology of the eye, St Louis, 2003, Mosby, pp 16."> Kikkawa DO, Lucarelli MJ, Shovlin JP, et al: Ophthalmic facial anatomy and physiology. In Kaufman PL, Alm A, editors: Adler’s physiology of the eye, St Louis, 2003, Mosby, pp 16.</ref> Tarsal plates then begin to develop, which eventually leads to the formation of meibomian glands. <ref name="PMID1628748"/> The ectoderm reflects over the developing cornea to form the conjunctival sac, a space that is filled by secretions from the lacrimal gland in order to allow smooth motions of the eyelid over the eye and also to clean the cornea and prevent accumulation of particles on the eye that may disrupt vision. By the time the eyelids separate, the eye has all its major components present (Figure 12), and further development consists mainly of growth and vascularisation.

[[File:Formation of the eyelid 1.jpg|400px|thumb|left|Fig.11: Small grooves in the ectoderm of the head - the precursors to an eyelid.]] [[File:Formation of the eyelid 2.jpg|400px|thumb|center|Fig. 12: The eye after week 8 of development. Note however, that the eyelids remain fused until weeks 26-28.]]

===Lacrimal Glands===

There are three stages of lacrimal gland development. The first is the presumptive glandular stage in which the superior conjunctival fornix epithelium thickens and the surrounding mesenchymal cells condense. These mesenchymal cells are of neural crest origin<ref><pubmed>9882499</pubmed></ref>. The second stage sees the development of nodular formations around the superior conjunctival fornix and the formation of lumina within the epithelial buds, this stage is therefore known as the bud stage. Innervation and vascularisation also occur during this stage. The final morphological changes occur during the glandular maturity stage which occurs in weeks 9-16 when the lacrimal glands begin to resemble the mature glands. During the 13th week the lacrimal and zygomatic nerves anastomose<ref><pubmed>14635806</pubmed></ref>.

These glands are responsible for the production of tears however they do not start to function until 1-3 months after birth. The mature lacrimal gland is made up of two lobes- the palpebral and orbital lobes.

==Current Research==

Not only are there still many important processes and components of eye development that we would like to understand, this knowledge also contributes to the development of treatments for eye disorders and technologies such as the bionic eye.

===The impact of visible light on the immature retina===

<pubmed>22405869</pubmed>

The authors mentioned in this article <ref name="PMID22405869"><pubmed>22405869</pubmed></ref> that they were interested in investigating the effect of light on postnatal eye development in mice, because mice are born with fused eyelids, which separate 12 days after birth. Before the eyelids separate, the retina develops in mice with very little radiation from light. It is believed that the darkness plays a role in the development of the retina in mice, which is why their eyelids are fused for 12 days after birth. Therefore the authors were interested to see what effect light would have on postnatal retinal development of mice, with special interest in retinal ganglion cells (RGC). In their experiment, they surgically opened the eyelids on the right eyes of some of the mice to expose them to visible light 12 hours per day, while they left some other mice in the dark after surgical separation of their eyelids. They also kept the left eyes of the mice naturally fused as controls in the experiment. Their results showed that early light exposure in mice causes a decrease in retinal ganglion cells because it affects cellular apoptosis in the retina. The authors also observed that early exposure to light in mice causes lumican mRna transcription to resume and to quickly increase. (Lumican normally stays silent in retina after birth).

---------

===GABA Maintains the Proliferation of Progenitors and Non-Pigmented Ciliary Epithelium===

<pubmed>22590629</pubmed>

{| width=800px
|-
| width=450px|
| width=350px|

|-
| GABA is an ‘inhibitory neurotransmitter’ in the central nervous system of adults. <ref name="PMID22590629"><pubmed>22590629</pubmed></ref> It is responsible for controlling proliferation of stem cells and progenitor cells. The authors of this article <ref name="PMID22590629"/> was interested to find the effects of GABA on proliferation of progenitor cells and non-pigmented ciliary epithelial cells (NPE) in the retina. Their study focused on progenitor cells and non-pigmented epithelium of the ciliary body in chickens. Non-pigmented epithelial cells in chickens arise from the neuroepithelium of the optic cup. They share similar functions as progenitors of the early retina, such as expression of Chx10 and Pax6 genes. It is not agreed upon whether epithelial cells of the ciliary body have stem cell properties. However, it has been found that these cells can be cultured and transplanted into retinas that are injured, in order to replace neurons that were previously lost. However, there is not much known about what factors regulate the proliferation of stem cells. Hence the authors were interested in finding the effects of GABA on proliferation of retinal cells. Their results showed that non-pigmented epithelial cells in chickens ‘express extrasynaptic-like GABAA receptors’ that have the ability to regulate cell proliferation. It has been found that inhibiting these ‘GABAA receptors’ also causes a decrease in proliferation of retinal progenitor cells and non-pigmented epithelial cells in 'the intact E8 retina’. <ref name="PMID22590629"/>

|
[[File:Gaba-effects-retina.JPG|thumbnail|250px|'''GABAA receptor mediated effects on retinal progenitor cell proliferation'''
]]
|}

-------------------------

===Stem Cells===

[http://www.advancedcell.com/patients/clinical-trial-information/ Advanced Cell Technology] is a biotechnology company which is currently running two clinical trials that utilise human embryonic stem cell derived retinal pigmented epithelial cells. These trials are examining the possibility of using these cells to treat stargardt's macular dystrophy and dry age-related macular degeneration.

Despite the discovery of human embryonic stem cells (hESCs) 13 years ago, these trials are the first to describe the subretinal transplantation of hESCs into humans. The participants in these trials were sufferers of Stargardt's macular dystrophy or dry age-related macular degeneration, which is the chief cause of blindness in the developed world.

The trials were relatively successful in the sense that the hESC-derived retinal pigment epithelium cells that were implanted integrated well into the existing tissue, and there were no signs of hyperproliferation, abnormal growth, or rejection. The authors hope that in future this technique will be applied to patients in the earlier stages of disease, preventing disease progression<ref><pubmed>22281388</pubmed></ref>.

-------------------

[[File:Bionic_eye.JPG|right|thumb|300px|Early prototype of the bionic eye.]]
===Bionic Eye===

[http://bionicvision.org.au/ Bionic Vision Australia] are the first organisation to implant a bionic eye. In 2012 a prototype made up of a retinal implant with 24 electrodes was implanted into 3 different patients with retinitis pigmentosa.

A camera is used to capture images which are transferred to an external data processing unit. From here the data is processed and transmitted via a wire to the implanted receiver, which in turn sends the signal to the retinal implant. The retinal implant is then able to stimulate the visual pathways in the brain.

Bionic Vision Australia hopes that in 2013, trials for a wide-view device that consists of 98 electrodes will be in progress. This prototype will be inserted into the suprachoroidal space in order to prevent mechanical damage to the retina. Trials for a more advanced high-acuity device with 1024 electrodes are planned for 2014. The electrode array contained in this device will be made of diamond to prevent irritation of surrounding tissues. These devices are expected to be suitable for patients with retinitis pigmentosa and age-related macular degeneration. The eventual goal will be to provide a completely wireless device which gives the patient high visual acuity.

----

===MIP/Aquaporin 0 Represents a Direct Transcriptional Target of PITX3 in the Developing Lens===

<pubmed>21698120</pubmed>

{| width=800px
|-
|PITX3 plays a siginificant role in the development of lens in vertebrates. If there is a deficiency is PITX3, it causes a range of problems in humans such as microphthalmia, Peter’s anomaly, or isolated cataracts. Mutation of PITX3 also causes degeneration of the lens in zebrafish and mice. It is therefore important to understand what factors may affect the decrease in PITX3, as a normal level of PITX3 is needed to maintain normal eye development. The authors wanted to investigate specific genes which are affected by PITX3. Previous research has shown that MIP and Aquaporin causes defects in the lens in both mice and humans. MIP and Aquaporin are targeted by PITX3, so their imbalance is interrelated in the cause of defects in the lens. Therefore it has been previously proven that PITX3 is needed for normal development of the lens. However, there has not been much information previously known regarding the exact effect that PITX3 has, or the specific genes it targets. Since MIP and Aquaporin is common genes found in humans, mice and zebrafish, the authors <ref name="PMID21698120"><pubmed>21698120</pubmed></ref> chose to study these genes to understand the pathway that PITX3 takes and its exact involvement in the development of the lens. Their results proved that deficiency in MIP and Aquaporin indeed affects normal development of the lens, and it is indeed related to deficiency in PITX3. However, there is still more research needed to understand PITX3 and the genes it interacts with, and their effect in ocular development.

|
[[File:Mip1-expression-in-pitx3.jpg|thumbnail|250px|'''Analysis of mip1 expression in pitx3-mo and control embryos via in situ hybridization and RT-PCR''']]
|}

-------------------

===Activation of c-Jun N-terminal kinase (JNK) during mitosis in retinal progenitor cells.===

<pubmed>22496813</pubmed>

{| width=800px
|-
| In the past, most studies about c-Jun N-terminal kinase (JNK) in the retina have been in relation to neurodegeneration. <ref name="PMID22496813"><pubmed>22496813</pubmed></ref> Therefore the authors in this article were interested in investigating the function of c-Jun N-terminal kinase in the retinal progenitor cells in neonatal rats. <ref name="PMID22496813"/> In the experiment, they took retinal tissue from newborn rats and fixed them, and subsequently examined them using confocal microscopy and fluorescence to discover c-Jun N-terminal kinase ‘phosphorylation by immunohistochemistry’. <ref name="PMID22496813"/> Mitotic cells in the retina were identified during the experiment. The results of their experiment revealed that c-Jun N-terminal kinase is phosphorylated in the developing retina of neonatal rats during the mitosis of progenitor cells. <ref name="PMID22496813"/> This shows that c-Jun N-terminal kinase can control the proliferation of progenitor cells in the developing retina. Their experiment also revealed that inhibiting c-Jun N-terminal kinase causes disruptions to the mitotic cell cycle by reducing the cell numbers in anaphase. <ref name="PMID22496813"/> However, inhibiting c-Jun N-terminal kinase did not change the cell numbers in metaphase or prophase. <ref name="PMID22496813"/>

|
[[File:JNK1.png|thumbnail|300px|'''"JNK is phosphorylated during mitosis of retinal progenitor cells."''']]
|}

----------------------------

===LRP5 is required for vascular development in deeper layers of the retina===

<pubmed>20652025</pubmed>

{| width=800px
|-
|
The lipoprotein receptor-related protein 5 (LRP5) has a significant function in the development of retinal vasculature.<ref name="PMID20652025"><pubmed>20652025</pubmed></ref> Research has shown that mutations of the LRP5 causes loss of function, due to incomplete development of retinal vessel network, in both humans and mice. The authors investigated how mutations occur in the LRP5, which leads to abnormal development of the retinal vasculature. They have studied retinal endothelial cells in mutant mice in their study. Their results showed that in retina with mutated LRP5, endothelial cells in the retinal vasculature primarily produced cell clusters in the inner-plexiform layer instead of migrating into deeper layers of the retina to form normal retinal vasculature. The authors also discovered that there was a decrease in Slc38a5, which is “a Müller cell-specific glutamine transporter”, in mice with mutated LRP5. Their results lead the authors to conclude that normal LRP5 is very important in the development of normal retinal vasculature due to their role in causing migration of retinal endothelial cells in the deeper layers of the retina. LRP5 is also important for retinal interneurons and Müller cells to function correctly.

|
[[File:Retina-cell-clusters.JPG|350px|thumbnail|'''Endothelial cells form thick clusters in the LRP5 mutant retina''']]
|}

-----------------

===Astrocyte-Derived Vascular Endothelial Growth Factor===

<pubmed>20686684</pubmed>

{| width=800px
|-
|
Vascular endothelial growth factor (VEGF) has an important role in normal development of retinal vasculature. <ref name="PMID20686684"><pubmed>20686684</pubmed></ref> In the process of vascularisation of the retina, the retinal astrocytes (both vascularised and not yet vascularised) expresses the vascular endothelial growth factor. <ref name="PMID20686684"/> This fact indicates that vascular endothelial growth factor that are derived from astrocytes of the retina plays an important role in vessel maturation and angiogenesis. <ref name="PMID20686684"/> Therefore the authors wanted to test the role of vascular endothelial growth factor that are derived from astrocytes to find further confirmation. ‘Cre-lox technology’ was used in the experiment to remove the vascular endothelial growth factor from mice retinal astrocytes in the developmental period. <ref name="PMID20686684"/> The results showed that removing vascular endothelial growth factor that are derived from astrocytes caused ‘the regression of smooth muscle cell-coated radial arteries and veins’ from the effects of hyperoxia. <ref name="PMID20686684"/> Hence, this result indicates that vascular endothelial growth factor plays an important role in stabilising blood vessels during the development of the retinal vasculature. <ref name="PMID20686684"/> It has been suggested that this finding may be of relevance to retinopathy in premature neonatal humans. <ref name="PMID20686684"/>

[[File:Astrocyte-vegf-deletion.JPG|250px|thumbnail|'''"Astrocyte specific deletion of VEGF." ''']]
|
[[File:Effect-of-vegf-on-retinal-vasculature.JPG|250px|thumbnail|'''"Effects of astrocyte-derived VEGF on retinal vascular development."''']]
[[File:Vegf-protects-vessels.JPG|250px|thumbnail|'''Astrocyte-derived VEGF protects vessels from hyperoxia. ''']]

|}

==Useful Links==

{{External Links}}

[http://www.youtube.com/watch?v=Xme8PA6xv-M Visualisation of eye development in the embryo]

[http://www.youtube.com/watch?v=wJE6pYwAMVU Brief Video on Embryonic development of the eyes]

[http://www.embryo.chronolab.com/sense.htm Embryonic Development of the eye]

[http://webvision.med.utah.edu/book/ Webvision free online textbook]

[http://www.ophthobook.com/chapters/ Free basic online book about the eyes]

[http://www.youtube.com/watch?v=deEjbVdnwyA&feature=related Anatomy of the Eyes- Video]

[http://www.vetmed.vt.edu/education/curriculum/vm8054/eye/EMBYEYE.HTM Simple eye embryology explanation]

==Glossary==

'''Accommodation''' - changing the focal length of the lens in order to focus on an object.

'''Anterior chamber''' - Fluid-filled area located between the iris and cornea.

'''Choroid''' - The middle coat of the eye, located between the sclera and retina, which contains blood vessels that nourish the structures in the eye.

'''Ciliary body''' - Structure located behind the iris which secretes aqueous humour. It contains ciliary muscle, which is involved with changing the shape of the lens for accommodation.

'''Cornea'''- a transparent section in the anterior of the eye which acts as a window over the pupils, and is involved with refracting light as it enters the eye.

'''Downstream genes''' - genes that are activated by other "upstream genes".

'''Ectoderm''' - outermost layer of germ cells in an early embryo.

'''Endoderm''' - innermost layer of germ cells in an early embryo.

'''Extraocular muscles''' - Muscles that control the movement of the eyeball.

'''Glial cells''' - non-neuronal cells that provide structure and protection to neurons as well as producing myelin.

'''Inductive signaling''' - a process whereby the secretion of factors from one cell or tissue triggers a response in another.

'''Iris'''- A circular shaped muscle which controls the opening and contraction of the pupil.

'''Lens'''- A structure inside the eye which refracts light as it enters the eye for clear vision.

'''Lens vesicle''' - the cavity of invaginated ectoderm from the optic placode that will form the lens.

'''Macula''' - a highly pigmented, oval-shaped area located near the centre of the retina. Important for visual acuity.

'''Mesenchyme''' - undifferentiated, loose connective tissue.

'''Mesoderm''' - middle layer of germ cells in an early embryo.

'''Mesothelium''' - the epithelial layer of the mesoderm.

'''Myelinisation''' - development of a myelin sheath around a nerve fibre.

'''Neural crest''' - a portion of the ectoderm situated next to the neural tube.

'''Neural groove''' - a large invagination on the dorsal surface of the embryo which will close off and form the neural tube.

'''Neural tube''' - hollow structure that results from the folding of the neural plate and eventually forms the central nervous system.

'''Neuroblastic layer''' - a layer of immature cells that differentiate to form either glial cells or neurons. The retina has two of these (an inner and outer).

'''Neuroectoderm''' - portion of the ectoderm that develops to form the central and peripheral nervous systems.

'''Optic chiasm''' - the point at which the optic nerves meet and cross over.

'''Optic cup''' - the structure that is formed after the optic vesicle folds in upon itself. This will form the retina.

'''Optic globe''' - a term that refers to the optic cup, lens vesicle and surrounding mesenchyme collectively.

'''Optic Nerve''' - The nerve which carries visual information from the retina to the brain for processing.

'''Optic placode''' - area of thickened ectoderm that gives rise to the lens of the eye.

'''Optic stalk''' - a long, narrow cavity that will produce the optic nerve.

'''Optic vesicle''' - a cavity that buds off from the neural tube and gives rise to the optic cup.

'''Posterior chamber'''- Fluid-filled area located between the iris and lens.

'''Pupil'''- opening in the anterior part of the eye, which controls how much light enters the eye.

'''Retina''' - Light-Sensitive portion located towards the back of the internal surface of the eye, which contains photoreceptors (rods and cones) which detects visual information and transmits it to the brain through the optic nerve.

'''Sclera'''- white part of the external anterior surface of the eye, which envelopes the eyeball to give it support and protection of its internal contents.

'''Upstream genes''' - genes that activate one or more other "downstream genes".

'''Vascularise''' - to invade with blood vessels.

'''Vitreous Chamber'''- Area located between the lens and retina, which contains vitreous (a jelly like substance) whose function is to maintain the shape of the eye.

==Image Gallery==
<gallery>
Image:Eye_diagram_bandw.jpg‎ | Basic structure of the human eye.
Image:Eyediagramcolour1.JPG | Basic anatomy of the eye.
Image:Stage14 sem2b-limb.jpg | A Stage 14 embryo showing the location of an otic placode.
Image:Stage 13 image 060.jpg | A cross section showing the organisation of the developing brain, the optic vesicle and the lens (optic) placode.
Image:Formation of the optic vesicle 1.jpg | Early formation of the optic vesicle from the neural groove.
Image:Formation of the optic vesicle 2.jpg | The optic vesicle at a later stage, showing the optic stalk.
Image:Formation of the optic nerve and chiasm 1.jpg | A recognisable brain and eye structure in later development.
Image:Formation of the optic cup 1.jpg | Mechanism of optic cup formation.
Image:Formation of the optic cup 2.jpg | Layers of the optic cup in retina development.
Image:Formation of the retina 1.jpg | Cross-section of the primitive retina showing cell types and layers.
Image:Formation of the retina 2.jpg | Cross-section of a developed retina showing cell types and layers.
Image:Formation of the lens 1.jpg | The importance of the optic cup in lens differentiation.
Image:Formation of the lens 2.jpg | The lens placode separates from the ectoderm and migrates into the mesoderm forming the lens vesicle.
Image:Formation of the choroid and sclera 1.jpg | The choroid and sclera derives from mesenchyme surrounding the optic cup.
Image:Formation of the eyelid 1.jpg | Small grooves in the ectoderm of the head - the precursors to an eyelid.
Image:Formation of the eyelid 2.jpg | The eye at an advanced stage of embryonic development. Note however, that the eyelids remain fused until much later.

</gallery>

==References==
<references/>

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--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

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{{2012Projects}}

2012 Group Project 1

2012-10-03T01:26:43Z

Z3254758: /* Stem Cells */

[[File:Eye_collage_2.jpg|right|830px]]

=Vision Development=

==Introduction==

Eyes are an important sensory organ shared across many different species and allow organisms to gather useful visual information from their environment. The visual system uses light from the environment and processes this information in the brain for visual perception. The visual system is complex, and is made up of various structures that work together to form vision. Each of the structures in the eye have specific tasks which contribute to the visual system. Knowledge of how the eye develops extends as far back as Aristotle more than 2000 years ago, and current knowledge shows that most of the crucial events of eye development occur in the embryological stage. The eye is an interesting model for studying the development of tissues in organisms, as it consists of cells from several parts of the embryo including the head ectoderm, neural ectoderm and mesoderm. From its many origins the cells come together and differentiate to produce the complex organ that is the eye. During this period there are many examples of inductive signaling, as the tissues coordinate their development throughout this elegant process.

The main anatomical structures of the eye are as follows:
{|
|
* Cornea

* Sclera

* Choroid

* Iris

* Ciliary body

* Lens

* Anterior chamber

* Posterior chamber

* Retina

* Optic nerve

|[[File:eye_diagram_bandw.jpg|right|250px|thumb|Basic structure of the human eye.]]
|[[File:Eye-pupil-sclera-iris.jpg|thumbnail|200px|Illustration of the front of the eye, showing the sclera, iris and pupil.]]
|}
[[File:Eyediagramcolour1.JPG|550px]]

==Research History==

=== '''Brief Timeline of Historical Developments on the Eye and its Embryology''' ===

{| width=800px
|-bgcolor="CEDFF2"
| width=100px|'''Time'''
| width=700px|'''Discovery'''

|-bgcolor="F5FAFF"
| '''Ancient Egyptians'''
| First to document cataracts. It is described as being 'the white disease of the eye' or 'darkening of the pupil.' <ref>Edwards, D.D. (1996). Ophthalmology before Hippocrates. In the History of Ophthalmology, ed. D.M. Albert and D.D. Edwards. Cambridge, Mass.: Blackwell Science.</ref> The Egyptians had some knowledge of the eye, however it is not known how much of the anatomy of the eye was known in their era.

|-bgcolor="CEDFF2"
| '''535 BC'''

|
Ancient Greek philosopher Alcmaeon conducted dissection of humans for the first time in recorded history. This included dissection of the eye. However, not much is known about which anatomical features he discovered. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17.">Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17.</ref>

|-bgcolor="F5FAFF"
| '''384- 322 BC'''

| [[File:Aristotle-eye.jpg|200px|thumbnail|The eye according to Aristotle.<ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "> Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau </ref> Note the lens is missing, and there are three vessels drawn that was believed to transport fluid to and from the eye.<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
]]
Aristotle performed dissections of animal embryos.<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

When Aristotle described the embryo of a ten day old chicken, he wrote "The eyes about this time, if taken out, are larger than beans and black; if their skin is removed the fluid inside is white and cold, shining brightly in the light, but nothing solid." <ref name="Magnus, H. (1998). Ophthalmology of the ancients. In J. Hirschberg (Ed.), The History of Ophthalmology: The monographs, Vol. 4, Part 1 (F.C. Blodi, Trans.) Bonn: Wayenborgh.">Magnus, H. (1998). Ophthalmology of the ancients. In J. Hirschberg (Ed.), The History of Ophthalmology: The monographs, Vol. 4, Part 1 (F.C. Blodi, Trans.) Bonn: Wayenborgh.</ref>

Aristotle believed that the eyes started forming during early embryogenesis, however, he also believed that the eyes are the last organs to form completely, and he incorrectly thought that the eyes shrink in later embryonic development. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press.">Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press.</ref> .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"

| '''340 BC'''

| Lens is thought to have been discovered by Hippocrates, due to his descriptions of the contents of the internal eye There has been studies in chick development later on by followers of Hippocrates. They claimed that eyes were visible in early embryogenesis. .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
|-bgcolor="F5FAFF"
|'''25 BC - 50 AD'''

| [[File:Celsus-eye.jpg|150px|thumb|The eye according to Celsus. <ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "/>
Note the lens is placed in the centre of the eye, in the vitreous.<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> ]]

Aulus Cornelius Celsus wrote a Roman medical text called 'De Medicina' in which he wrote that the lens was the part of the eye from which vision originated. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.">Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.</ref> Celsus also incorrectly drew the lens in the center of the globe in his diagram of the eye. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

|-bgcolor="CEDFF2"
| '''23-79 AD '''
|
Pliny the Elder said that the eye is the last of the organs to develop in the womb <ref name="Magnus, H. (1998). Ophthalmology of the ancients. In J. Hirschberg (Ed.), The History of Ophthalmology: The monographs, Vol. 4, Part 1 (F.C. Blodi, Trans.) Bonn: Wayenborgh."/>
|-bgcolor="F5FAFF"
| '''98-117 AD'''

| [[File:Rufus-eye.jpg|150px|thumb|The eye according to Rufus of Ephesus. <ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "/>
Note the lens is placed in the correct position, behind the iris of the eye <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> ]]

Rufus of Ephesus identified the lens as being located in the anterior part of the eye, close to the pupil. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

His diagram illustrates that he knew the correct position of the lens as being directly behind the iris, in the anterior part of the eye, and not in the centre as was previously depicted by others before him.

|-bgcolor="CEDFF2"
| '''130-200 AD'''

| [[File:Galen-eye1.jpg|150px|thumb|The eye according to Galen. <ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "/> ]]

Claudius Galen practised medicine in Rome. He wrote:

"1. Within the eye the principal orgran of sensation is the crystalline lens.

2. The sensation potential comes from the brain and is conducted via the optic nerves.

3. All other parts of the eyeball are supporting structures." <ref> Hirschberge, J. (1982). Antiquity, Vol. X in the History of Ophthalmology (F.C. Blodi, Trans.) Bonn: Wayenborgh. pp. 280 </ref>

Galen thought that the lens was produced from the vitreous. He also believed that the retina’s function was to give nourishment to the lens and vitreous, and to carry visual information to the brain from the lens. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

|-bgcolor="F5FAFF"

| '''1514-1564'''

| Andreas Vesalius published his anatomy book "De Humani Corporis Fabrica in 1543. He had the misconception that the lens was located in the centre of the eyeball. .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> He also wrote that the lens functioned "like a convex lens made of glass" <ref name="Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.">Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.</ref> pp. 48
|-bgcolor="CEDFF2"
| '''1535-1606'''

| Georg Bartisch correctly drew a diagram of the lens placed behind the iris in his book 'Ophthalmodouleia: das ist Augendienst'. <ref name="Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>
|-bgcolor="F5FAFF"

| '''1537-1619'''

| Fallopio Hieronymus Fabricius ab Aquapendente studied anatomy and embryology. He studied chicken embryos, and thought that chalazae (which comes from egg white) gives rise to the eyes. He also drew the lens directly behind the iris in a diagram in is book 'Tractatus de Oculo Visuque Organo. <ref name="Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

|-bgcolor="CEDFF2"
| '''1583'''

| Felix Platter published his book 'De corporis Humani Structura et Usu, after he performed dissections of human bodies. He believed that the retina is the primary visual organ in the eye. .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="F5FAFF"
| '''1619'''
| Scheiner is given credit to be the first person to correctly draw the diagram of the anatomy of the eye. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
|-bgcolor="CEDFF2"
| '''1672'''
| Marcello Malpighi described the embryonic development of the chicken. He drew many detailed diagrams of the chick eye. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1665'''
| Nicolaus Steno identified the choroid fissure in his study of a developing embryo of a chicken. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="CEDFF2"
| '''1754'''

| Albrecht von Haller studied the embryology of the eye. With help from his student Johann Gottfried Zinn, he contributed to the understanding of the development of the ciliary body, ciliary zonule, and their relationship with the lens and vitreous. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1817'''

| Christian Pander discovered the three embryonic germ layers, which he wrote about in his book. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/> Pander was the first to think of 'the optic vesicles as lateral evaginations' of the 'prosencephalon'; however, he was incorrect about the details regarding how 'the eye develops from these evaginations'. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="CEDFF2"
| '''1828-1837'''

| Karl Ernst von Baer studied embryology. He discovered that the optic vesicles were 'outgrowths of the embryonic forebrain' <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> which he believed was caused by pressure from fluids in the central nervous system. Von Baer also believed that the optic vesicle opens to form the pupil, and that fluid in the optic vesicle coagulates to form the vitreous body and lens. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1830'''

| Emil Huschke discovered that the lens forms from the invagination of the surface ectoderm. He concluded that the lens hence does not form ‘from the fluid of the optic vesicle’ <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> as previously thought.
|-bgcolor="CEDFF2"
| '''1832'''

| Emil Huschke wrote in his manuscript ‘Ueber die erste Entwinkenlung des Auges und die damit zusammenhängende Cyklopie’ that the lens capsule forms from the outer surface ectoderm, which detaches and moves back inward, which is later enclosed again by several membranes, such as by the cornea. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

Huschke also described how the optic cup and choroid fissure forms. He discovered that the optic vesicles are produced from the two-layered optic cup. However, he incorrectly described the destiny of the ‘individual optic cup layers’. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

|-bgcolor="F5FAFF"
| '''1838'''
| Matthias Jakob Schleiden and Theodor Schwann formulated the ‘cell theory’: “All living things are formed from cells, the cell is the smallest unit of life, and cells arise from pre-existing cells.” <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
|-bgcolor="CEDFF2"
| '''1839'''

| Theodor Schwann contributed a better understanding of the development of the lens through studying the foetus of a pig, which he wrote about in his book ‘Mikroskopische Untersuchungen Über Die Uebereinstimmung in Der Struktur Und Dem Wachsthum Der Thiere Und Pflanzen’. He wrote that the lens is made of ‘concentric layers’ of fibres which proceeds from an anterior to posterior direction. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1842'''
| Robert Remak gave the current names to the three embryonic germ layers: ectoderm, mesoderm and endoderm. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"
| '''1843'''
| Wilhelm Werneck published his book ‘Beiträge zur Gewebelehre des Kristallkörpers’. He wrote that the contents inside of the lens is not made of fluids, as was previously believed. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/> Werneck also discovered that the fibers of the lens continues to grow from the outside to the centre during embryogenesis. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

|-bgcolor="F5FAFF"
| '''1855'''

| Robert Remak wrote his book ‘Untersuchungen über die Entwickelung der Wirbelthiere’. He wrote about what he discovered in his studies of the development of the eye in the embryos of chickens, frogs, and rabbits. He wrote very descriptively about the embryology of lens formation, amongst other topics. He discovered that the ectoderm gives rise to the lens placode. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

|-bgcolor="CEDFF2"
| '''1858'''
| Henry Gray published his book 'Anatomy, Descriptive and Surgical'. He had also previously studied the embryonic development of the optic nerve and retina of chickens.
|-bgcolor="F5FAFF"
| '''1877'''
| Paul Leonhard Kessler wrote about the embryonic development of the lens in mice in his book ‘Zur Entwickelung des Auges der Wirbelthiere. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"
| '''1891'''
| Vincenzo Colucci studied newts and discovered their ability to regenerate the lens.<ref> Tsonis, P. A. (2001). Regeneration of the Vertebrate Lens and Other Eye Structures. eLS. (Online Publication). DOI: 10.1038/npg.els.0001102 </ref>
|-bgcolor="F5FAFF"
| '''1892'''
| Dr. Oscar Hertwig published his book ‘Text-Book of the Embryology of Man and Mammals. <ref> Hertwig, O. Text-book of the embryology of man and mammals. S. Sonnenschein 1901. (Translated from the 3d German ed. by Edward L. Mark.) </ref> It contains a very detailed description of the development of the eye, according to the findings at that time. [http://embryology.med.unsw.edu.au/embryology/index.php?title=Book_-_Text-Book_of_the_Embryology_of_Man_and_Mammals_16-2#The_Development_of_the_Eye]
|-bgcolor="CEDFF2"
| '''1895'''
| Gustav Wolff also independently studied newts and discovered their ability to regenerate the lens. .<ref> Tsonis, P. A. (2001). Regeneration of the Vertebrate Lens and Other Eye Structures. eLS. (Online Publication). DOI: 10.1038/npg.els.0001102 </ref>

|-bgcolor="F5FAFF"

| '''1900'''
| Carl Rabl published his book ‘Uber den Bau und die Entwicklung der Linse’. He wrote about the development of the lens in mammals, fish, birds, reptiles, and amphibians. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"
| '''1901'''
| Hans Spemann published his findings from his experimental studies about the formation of the lens in the frog. He found that the optic cup needed to be in contact with the ectoderm for normal development of the eye. <ref> Spemann, H. (1901). Über Correlationen in der Entwicklung des Auges. Verhand. Anat. Ges. 15: 61-79. </ref> <ref> Saha, M. (1991). Spemann seen through a lens. In Gilbert, S. F. (ed.). A Conceptual History of Modern Embryology. Plenum Press, NY. pp. 91-108.</ref>
|-bgcolor="F5FAFF"
| '''1906'''
| Brown ‘s book “The Embryology Anatomy and Histology of the Eye” was published. It contained detailed descriptions of the embryonic development of the eye according to the knowledge current at that time, mainly based on observations from embryos of rabbits and chickens. <ref> Brown, E.J. (1906). The Embryology Anatomy and Histology of the Eye. Chicago: Hazlitt & Walker. 1906 </ref>

|-bgcolor="CEDFF2"
| '''1907'''

| John Clement Heisler published his book ‘A Text-book of embryology’. It contains a chapter detailing the embryonic development of the eye, according to the knowledge current at that time. The book’s copyright has expired, so it can be viewed free online: [http://archive.org/details/atextbookembryo01heisgoog]

Julius Kollman also published his book 'Atlas of the Development of Man'. It contained very detailed description and illustrations showing the embryonic development of the human according to the knowledge current at that time. His illustrations were reused by many others after his time and built upon for further refined understanding of the embryology of the human.

Here are examples of Julius Kollman's excellent illustrations showing eye development in various stages:

'''Formation of Primary Optic Vesicle:'''
<gallery>
File:Kollmann691.jpg|The blue part at the bottom is the endoderm. The pink middle layer is the mesoderm. The top yellow layer is the ectoderm. The fold labelled as 'augenfeld' is the place where the optic vesicle will form.
File:Kollmann692.jpg|The eye area (augenfeld) is a bowl shaped bulge still located on the side walls.
File:Kollmann693.jpg| The neural tube is shown after removal of all of the ectoderm and ventral organs, such as heart, gut tube, etc. The primary optic vesicle forms a slightly flattened hollow protrusion on the forebrain.
File:Kollmann694.jpg|The lateral surface of the primary optic vesicle is slightly depressed, showing the first sign of the emergence of the secondary optic vesicle
</gallery>

'''Development of Lens:'''

<gallery>
File:Kollmann695.jpg|The bulging lateral wall of the primary optic vesicle is covered by a fairly well demarcated lens plate, a direct continuation of the ectoderm. Between the optic vesicle and the lens pit are some flattened spindle-shaped cells. In the adjoining mesoderm are cross-sections of capillaries.
File:Kollmann697.jpg|The lens still hangs together with the ectoderm. The primary eye vesicle is indented with respect to the lens. Between the lens and the lateral plate of the optic vesicle is a narrow space, which allows area to further develop later.
File:Kollmann698.jpg|4th Week of development. The internal organisation shows the secondary optic vesicle. A: The rear wall of lens is noticeable and is enveloped by mesoderm. B: The edges of the lens pit is already grown and the lens vesicles are formed, which is still related to the remaining ectoderm.
File:Kollmann699.jpg|The lens has now cut off from the ectoderm, but is still very superficial. Between it and the lateral lamina of the optic cup, there is a considerable space. The eye stalk has become longer and is enclosed together with the optic cup and lens of the mesoderm. The cornea, sclera and choroid make gradual development.
</gallery>

|-bgcolor="F5FAFF"

| '''1921'''
| Bailey and Miller published their textbook “Text-Book of Embryology “. <ref> Bailey, F.R. and Miller, A.M. (1921). Text-Book of Embryology. New York: William Wood and Co. (Note- This book is only at an early edited stage)</ref> It contains detailed description of the development of the embryonic eye according to the knowledge current at that time. [http://embryology.med.unsw.edu.au/embryology/index.php?title=Book_-_Text-Book_of_Embryology_18]

|-bgcolor="CEDFF2"
| '''1925'''

| Mann published his research article, in which he gives a detailed account of the development of the human iris. He divided the development of the iris into four stages: weeks 4-7 (before the ectodermal iris forms or before the anterior chamber forms); weeks 7-11 (anterior chamber appears, and mesodermal iris forms); weeks 11-12 (ectodermal iris forms); 3-8 months (muscles of the pupil forms from ectodermal iris, and the central portion of the mesodermal iris atrophies to make the pupil clear). <ref name="PMID18168466"><pubmed>18168466</pubmed></ref>
O Leser also published an article detailing the development of extraocular muscles in mammals he studied. <ref name="PMID18168498"><pubmed>18168498</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1939'''
| Holtfreter <ref> Holtfreter, J. (1939). Gewebeaffinitat, ein Mittel der embryonalen
Formbildung. Arch. Exp. Zellforsch. 23, 169-209. </ref> studied amphibians and observed that that the development of the eye stops at the ‘optic vesicle stage’ if there is no contact ‘with the epidermis and neural crest driven mesenchyme’. <ref name=”PMID11023863”><pubmed>11023863</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1955'''
| Barber published his book ‘Embryology of the human eye’. <ref> Barber AN: Embryology of the human eye. St. Louis. CV Mosby 1955</ref> In contains detailed descriptions of the embryological development of the human eye according to the knowledge current at that time. It contains many photographs of the eye at different stages of development.

|-bgcolor="F5FAFF"
| '''1957'''
| Coulombre studied a chicken embryo to find the role of intraocular pressure in the development of the chick’s eye, especially in regards to its control of the size of the eye structures. <ref name="PMID13469954"><pubmed>13469954</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1958'''
| Coulombre studied the development of the cornea and how it develops its transparency. <ref name="PMID13563560"><pubmed>13563560</pubmed></ref> He also studied the development of corneal curvature. <ref name="PMID 13519969"><pubmed> 13519969</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1962'''
| Coulombre studied the development of the conjunctival papillae and scleral ossicles. <ref name="PMID 14023393"><pubmed> 14023393</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1963'''
| Coulombre studied the development of lens fibers and their orientation. <ref name="PMID14077035"><pubmed>14077035</pubmed></ref> He also studied the development of pigmented epithelium. <ref name="PMID14023394"><pubmed>14023394</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1964'''

| Coulombre further studied the development of the lens to determine the role of the lens in eye growth. <ref name="PMID14189921"><pubmed>14189921</pubmed></ref> He also studied the role of thyroid in the development of the cornea and the development of corneal transparency. <ref name="PMID14211912"><pubmed>14211912</pubmed></ref> Mann also published his work called ‘The development of the human eye’, which contains detailed description of the embryonic development of the eye according to current knowledge at that time. <ref> Mann I. The development of the human eye. New York: Grune and Stratton 1964</ref>

|-bgcolor="CEDFF2"
| '''1965'''
| Coulombre published his findings regarding the regeneration of the neural retina from pigmented epithelium in the embryo of chickens. <ref name="PMID5833111"><pubmed>5833111</pubmed></ref> Smelser also published his findings on the embryological development and morphology of the lens. <ref name="PMID14340157"><pubmed>14340157</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1966'''

| Formation of the face and orbit occurs from the differentiation of neural crest cells. <ref name="PMID5969670"><pubmed>5969670</pubmed></ref> O’Rahilly also published findings of the development of the eye in the early stages of human embryos. <ref> O'Rahilly, R. 1966 The early development of the eye in staged human embryos. Contr. Embry. Carnegie Inst., Wash., 38: 1–42</ref>

|-bgcolor="CEDFF2"
| '''1968'''
| Findings of the postnatal development of the retina of rats was published. <ref name="PMID5640327"><pubmed>5640327</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1969'''

| Mann again published his work called ‘The development of the human eye’. He stated that that the lens in humans forms completely from the ectoderm. <ref name=”Mann I. The Development of the Human Eye. New York, USA: Grune & Stratton, Inc; 1969”> Mann I. The Development of the Human Eye. New York, USA: Grune & Stratton, Inc; 1969</ref> Coulombre also studied the development of the lens, and took note of its size, shape and orientation throughout its developmental stages. <ref name="PMID 5772716"><pubmed> 5772716</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1970'''
| Coulombre again further studied the regeneration of the neural retina from pigmented epithelium of embryos of chickens. <ref name="PMID 5472476"><pubmed> 5472476</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1971'''

| Coulombre further studied the development of the lens. This time he focused on analysing the histological mechanisms in the reconstitution of the lens from implanted lens epithelium. <ref name="PMID 4925671"><pubmed> 4925671</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1973'''
| A research article was published, detailing the embryonic development of the retina of humans. <ref name="PMID 6650859"><pubmed> 6650859</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1976'''

| Geeraets published his observations of the closure of the embryonic optic fissure in golden hamsters, using the electron microscope. <ref name="PMID 1266776"><pubmed> 1266776</pubmed></ref> Kornneef also published an article based on his studies of the development of connective tissue in the human orbit. <ref name="PMID 1020699"><pubmed> 1020699</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1981'''
| A research article was published detailing how myelin forms in the optic nerve of humans. <ref name="PMID 7224936"><pubmed> 7224936</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1983'''
| O’Rahilly’s further research developments was published, reporting the timing and sequence of events in the development of the embryonic human eye. <ref name="PMID 6650859"><pubmed> 6650859</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1990'''

| Van Driell et al. <ref>Driell, D. Van; Provis, J.M.; Billson, F.A.: Early differentiation of ganglion, amacrine, bipolar and Muller cells in the developing fovea of the human retina. J. Comp. Neurol. 291: 203-219.</ref> studied the manner in which amacrine, bipolar, retinal ganglion cells, and Muller cells differentiate in the developing fovea of the retina of a 15-week old human foetus. <ref name="PMID1628748"><pubmed>1628748</pubmed></ref> Tripathy also published an article providing evidence that the lacrimal glands in humans originates from the neuroectoderm. <ref name="PMID2406219"><pubmed>2406219</pubmed></ref>

|}

==Development, Structure and Function of Ocular Components==

The eye itself is formed from several components; notably the optic placode of the head ectoderm, the optic vesicle from the neural tube, and mesenchyme from the mesoderm and neural crest cells. The optic placode contributes the lens to the eye, the optic vesicle gives rise to layers of the retina, while the mesenchyme will produce the ciliary body, iris, choroid and sclera.<ref>http://www.vetmed.vt.edu/education/curriculum/vm8054/eye/EMBYEYE.HTM</ref> Cells from the neural tube will also produce the optic nerve, which receives nerve impulses from the retina of the eye. Eyes initially form as laterally paired structures and migrate medially in the human embryo. In other animals such as birds and lizards, the eyes do not migrate and develop laterally on the head. The optic placodes become prominent on the surface of the embryo at approximately Stage 14 of development.

[[File:Stage14 sem2b-limb.jpg|200px|thumb|left|A Stage 14 embryo showing the location of an otic placode.<ref name="http://embryology.med.unsw.edu.au/embryology/index.php?title=ANAT2341_Lab_6_-_Early_Embryo">http://embryology.med.unsw.edu.au/embryology/index.php?title=ANAT2341_Lab_6_-_Early_Embryo</ref>]] [[File:Stage 13 image 060.jpg|400px|thumb|center|A cross section showing the organisation of the developing brain, the optic vesicle and the lens (optic) placode.<ref name="http://embryology.med.unsw.edu.au/embryology/index.php?title=ANAT2341_Lab_6_-_Early_Embryo"/>]]

===Optic Nerve===

The optic nerve consists of nerve fibres that transmit information from the retinal photoreceptor cells to the brain. The optic nerve is formed from the optic stalk, which develops as the optic vesicle migrates from its origin in the neural tube to its destination - the surface ectoderm - where it will fuse with the optic placode (also known as the lens placode, which will contribute the lens to the eye).<ref name="PMID11687490"><pubmed>11687490</pubmed></ref>

[[File:Formation of the optic vesicle 1.jpg|400px|thumb|left|Fig. 1: Early formation of the optic vesicle from the neural groove.]] [[File:Formation of the optic vesicle 2.jpg|400px|thumb|center|Fig. 2: The optic vesicle at a later stage, showing the optic stalk.]]

As can be seen in Figure 1 above, the optic vesicle forms from the neural tube. However, note that the neural tube has not yet closed, and is still the neural groove at this point. Figure 2 then shows the optic vesicle at slightly later stage in the same simplified cross-section of the embryo, as it migrates from the neural tube to the surface ectoderm. Note the presence of the optic stalk which links the optic vesicle to the neural tube. Later in development, this primitive structure will become the optic nerve, which will link the eye to the brain.

The nerve fibres themselves will initially originate from the retinal ganglion cells in the eye during week 6.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008">Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008</ref> After two weeks, these fibers will have grown along the inner wall of the optic stalk and have reached the brain. They grow both in length and width, with the nerve fibres filling the hollow optic stalk to form the solid optic nerve. More than one million nerve fibers will eventually make up the optic nerve, along with glial cells which arise from the inner wall of the optic stalk itself.<ref><pubmed>1451666</pubmed></ref> Myelinisation of the optic nerve begins much later in development at around 7 months, beginning at the optic chiasm and moving towards the eye.<ref><pubmed>7224936</pubmed></ref> The optic chiasm forms just before the nerves reach the brain, and is where half the nerve fibres from each eye will cross over to the opposite side of the brain. This is demonstrated in Figure 3. Note the crossing over of the optic nerves just before they enter the brain, at the optic chiasm. This organisation is now much more familiar, with the eyes near the ectoderm and the optic nerve leading through the mesoderm to the brain buried deep in the embryo.

[[File:Formation of the optic nerve and chiasm 1.jpg|400px|thumb|center|Fig. 3: A recognisable brain and eye structure in later development.]]

===Retina===

The retinal component of the eye is formed when the optic vesicle folds in upon itself, forming the optic cup (see Figure 4). In doing so it creates two layers - an inner wall and an outer wall of the optic cup (Figure 5). These two layers of the optic cup will give rise to the two layers of the retina - the inner neural retina, and the outer pigmented epithelium.<ref name="PMID11687490"/> Note the existence of the space between the two layers of the retina. This is known as the intraretinal space and disappears by the 7th week of development, however the two layers never completely fuse and can become separated as a result of physical trauma to the head - leading to a detached retina and loss of vision.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/>

The inner wall of the optic cup, which will give rise to the neural retina, consists of a layer of pseudostratified cells (see Figure 6) that later differentiate into rod, cone, bipolar, ganglion, horizontal, amacrine and glial cells of the retina (Figure 7).<ref name="PMID18168748"><pubmed>18168748</pubmed></ref> The outer wall of the optic cup consists of a layer of cuboidal cells that contain melanin - the light absorbing pigment. The function of this layer is to absorb light and prevent internal reflection of light within the eye, which would impair our ability to form distinct images. Interestingly, in some animals such as cats, this layer actually reflects light intentionally to increase the amount of light available to the eye in low-light conditions. This is why cats seem to have eyes that glow in the dark.<ref>http://dialspace.dial.pipex.com/agarman/bco/fact4.htm</ref>

[[File:Formation of the optic cup 1.jpg|400px|thumb|left|Fig. 4: Mechanism of optic cup formation.]] [[File:Formation of the optic cup 2.jpg|400px|thumb|center|Fig. 5: Layers of the optic cup in retina development.]]

The inner wall itself is divided into two components - the inner neuroblastic layer and the outer neuroblastic layer (see Figure 6). The outer neuroblastic layer forms the rod and cone cells while the inner neuroblastic layer forms the remaining cell types found in the retina - the bipolar, ganglion, horizontal, amacrine and glial cells (Figure 7).<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/> The organisation of the retina is interesting in that incoming light passes through several layers of these neural retina cells before it is detected by rod and cone cells at the back of the retina, and then nerve signals are passed back through the layers of neural retina cells that the light just passed through moments before - a seemingly strange design that the eye does not share with man-made light-capturing devices such as a camera (imagine putting the wires in front of the image sensor!).

Differentiation of the neuroblastic layers into neural retina cells occurs in a pattern both within the layers and across the retina. Cells differentiate from the inner neuroblastic layer to the outer neuroblastic layer, and differentiate from the central retina to the peripheral retina.<ref name="PMID18168748"/> The macula is first identifiable in week 22 when ganglion cells start to form multiple rows, and the primitive fovea begins to form at approximately the same time as a depression in the macula.<ref><pubmed>6462623</pubmed></ref> It is not until 15-45 months after birth that this area becomes exclusively populated by cone cells and becomes the fovea centralis - the area of the retina with the highest visual acuity.

[[File:Formation of the retina 1.jpg|400px|thumb|left|Fig. 6: Cross-section of the primitive retina showing cell types and layers.]] [[File:Formation of the retina 2.jpg|400px|thumb|center|Fig. 7:Cross-section of a developed retina showing cell types and layers.]]

===Ciliary Body===

The ciliary body consists of ciliary processes and three portions of fibres that constitute the ciliary muscles. It functions to maintain normal eye physiology as well as playing a direct role in accommodation.

During development, the ciliary processes form slightly posterior to the iris, developing from part of the anterior rim of the optic cup. It is thought that the folded structure of the ciliary processes is brought about by intraocular pressure and specific signalling pathways.<ref name="PMID16959249"><pubmed>16959249</pubmed></ref> While the ciliary muscles and the endothelial cells of the ciliary blood vessels are chiefly formed by mesenchymal cells<ref><pubmed>16249499</pubmed></ref>, the neural crest and neuroectoderm also contribute to their development.<ref><pubmed>12127103</pubmed></ref> The normal development of the ciliary body is dependent on the correct expression of bone morphogenetic protein (BMP)-4, which is a member of the transforming growth factor-β superfamily.<ref><pubmed>1222340</pubmed></ref> Napier and Kidson (2007) summarised numerous genes that have been associated with ciliary body development, however their direct roles have not been well documented.<ref name="PMID16959249"/>

===Iris===

The iris is a thin layer that develops at the end of the third month of development and is derived from the anterior rim of the optic cup. The stroma of the iris develops from cells of neural crest cell origin.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/> The muscles that are responsible for the dilation and constriction of the pupil (dilator pupillae and sphincter pupillae muscles) form from the neuroectoderm of the optic cup. These cells are initially epithelial cells that then transform into smooth muscle cells. <ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"></ref>. The invagination of the optic vesicle which creates the optic cup, also causes the formation of the optic cup lip. This is the region of the where the epithelium doubles back, separating the outer pigmented layer and the inner nonpigmented layer. This is the edge of the iris that borders on the pupil<ref><pubmed> Retinal and anterior eye compartments derive from a common progenitor pool in the avian optic cup</pubmed></ref>.

The final colour of the iris is not evident until the postnatal period. It is determined by a number of genes including IRF4, SLC24A4 and MATP<ref><pubmed>19710684</pubmed></ref>. Other features such as crypt frequency, furrow contractions, presence of peripupillary pigmented ring, and number of nevi also become evident during development<ref><pubmed>21835309</pubmed></ref>. Mutations in Pax6 have been shown to cause partial or complete loss of the iris <ref><pubmed>12386935</pubmed></ref>.

===Cornea===

The cornea is the transparent, avascular, most anterior portion of the eye. It is responsible for conducting light into the eye and focusing it on to the retina, as well as maintaining the rigidity of the eyeball. It consists of 5 layers- the epithelium, Bowman’s layer, stroma, Descemet’s membrane and the endothelium.

The epithelium and endothelium of the cornea first appear during the 5th week of gestation. The epithelium of the external surface of the cornea is derived from surface ectoderm, while the mesenchyme is derived from the mesoderm<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"/>. The endothelium is a two-cell cuboidal layer which is made up of differentiated neural crest cells that were initially from the optic cup. By week 8 the endothelial cells begin to secrete a basement membrance which later forms Descemet’s membrane<ref><pubmed>6511224</pubmed></ref>. At approximately 16 weeks gestation the Bowman’s membrane begins to form from the thickening of the stroma that is located under the corneal epithelium<ref>Riordan-Eva P, Whitcher JP. Vaughn and Asbury's General Ophthalmology, Lange Medical Books/McGraw Hill. 2004:25–27</ref>. During the third month glycosaminoglycans secreted by fibroblasts form the ground substance of the cornea, with collagen fibrils and keratan sulphate also appearing around this time. Shortly after this tight junctions form between the endothelial cells<ref><pubmed>19481138</pubmed></ref>. Fibroblast growth factor causes the epithelial cells to proliferate<ref><pubmed>20105280</pubmed></ref>.

Towards the end of the gestational period the cornea becomes larger due to the production of aqueous humor<ref>Yanoff M, Duker JS. Ophthalmology. Mosby; St. Louis, MO: 2004</ref>. The final transparent structure develops because hyaluronidase removes hyaluronic acid, thyroxine causes dehydration of the stroma, and the entire structure becomes avascular<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/>. Numerous genes have been implicated in the development of the cornea, these include, but are not limited to, PAX6, PITX2, FOXC1, MAF, TMEM114, SOX2, OTX2 and BMP4<ref><pubmed>18637741</pubmed></ref>. Pax6 and Pax6(5a) isoforms are essential for the normal development of the eye. Over or under expression can both lead to major structural abnormalities<ref><pubmed>18386822</pubmed></ref>.

===Lens===

The lens has its origin from the optic placode, which develops on the ectodermic surface of the embryo and migrates both medially and inwards into the embryo. The lens allows accommodation of the eye, and adjusts its thickness in order to focus on near or far objects. The study of lens development was one of the first to highlight the importance of inductive signaling in development, with Spemann's pioneering work at the start of the 20th century, finding that the absence of retinal development resulted in the absence of lens formation.<ref name="PMID11687490"/> Indeed, it has been consistently shown that the interaction of the migrating optic vesicle with the surface ectoderm of the head is vital in producing differentiation of the lens.<ref name="PMID15558475"><pubmed>15558475</pubmed></ref> The mechanism of interaction is complex but basically involves upstream genes switching on downstream genes, with the genes eventually producing specialised proteins which constitute the lens. The whole process starts with the signaling molecules from the optic cup initiating a thickening of the surface ectoderm of the head (Figure 8). It is thought that this region of specific ectoderm is responsive to the signaling molecules, as lens formation is incomplete or absent when ectoderm from the lateral portion of the embryo (i.e. non-head ectoderm) is exposed to the same inductive signaling processes.<ref name="PMID9216064"><pubmed>9216064</pubmed></ref> Pax6 has been shown to be one of the major genes required for differentiation of the lens, which in turn switches on transcriptional genes such as Sox 1, 2 and 3 among others - producing water-soluble proteins called crystallins - responsible for giving the lens its transparency and refractive properties.<ref name="PMID9609835"><pubmed>9609835</pubmed></ref>

[[File:Formation of the lens 1.jpg|400px|thumb|left|Fig. 8: The importance of the optic cup in lens differentiation.]] [[File:Formation of the lens 2.jpg|400px|thumb|center|Fig. 9: The lens placode separates from the ectoderm and migrates into the mesoderm forming the lens vesicle.]]

The lens placode invaginates from the head ectoderm and migrates into the mesoderm (Figure 9). Once this structure (now known as the lens vesicle) is in place opposite the optic cup, the combined structure is referred to as the optic globe and resembles a recognisable eye structure. The lens continues to differentiate further, as mentioned above, through the formation of crystallin proteins, which give the lens its unique properties and allows for the fine control over the degree of refraction that takes place.

===Aqueous Chambers===

There are both anterior and posterior aqueous chambers of the eye which contain aqueous humour. A space develops in the mesenchyme situated between the lens and cornea to form the anterior aqueous chamber. The mesenchyme located superficially to this chamber forms the mesothelium as well as the transparent portion of the cornea.

The posterior chamber develops from a similar space in the mesenchyme, however it is located between the iris and the lens. The anterior and posterior chambers are able to communicate with one another once the papillary membrane vanishes and the pupil is formed. This channel is known as the scleral venous sinus.<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011">Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011</ref>

Contained within the aqueous chambers is aqueous humor. The production of aqueous humor is dependant on the development of the ciliary body. It is produced in the ciliary processes and it’s production is a metabolic process driven by the delivery of oxygen and the removal of wastes via the ciliary circulation<ref><pubmed>20801226</pubmed></ref>.

===Choroid and Sclera===

The choroid and sclera are adjacent layers that surround the eye and act to vascularise and protect the eye respectively. They are formed from neural crest and mesoderm-derived mesenchyme which condenses around the optic cup and lens vesicle between weeks 5 and 7 of development to form a primitive eyeball structure known as the optic globe.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/> Blood vessels first start to appear in the choroid layer at approximately week 15, and arteries and veins can be distinguished by week 23.<ref>Development of the Choroid and Related Structures, K. Sellheyer, Eye (1990) 4, 255-261</ref> Inductive processes are thought to play a vital role during formation of the choroid and sclera; with the retinal pigmented epithelium inducing differentiation of the surrounding mesenchyme while at the same time the neural crest-derived mesenchyme contributing components to the retinal pigmented epithelium such as melanocytes.<ref name="PMID1628748"/> In addition to having functional roles themselves, the primitive choroid and sclera also contribute components to the developing ciliary body and cornea (Figure 10). In the adult eye, the choroid is continuous with the ciliary body and the sclera with the cornea.

[[File:Formation of the choroid and sclera 1.jpg|400px|thumb|center|Fig. 10: The choroid and sclera derives from mesenchyme surrounding the optic cup.]]

===Eyelids===

The eyelids are ectodermal and mesodermal in origin and are an extension of the skin which covers and protects the eye. The surface ectoderm gives rise to the conjunctiva, skin epithelium, hair follicles, cilia, Zeis glands, glands of Moll, and meibomian glands. <ref name=" Cook CS, Ozanics V, Jakobiec FA. (1994) Prenatal development of the eye and its adnexa. In Tasman W, Jaeger EA, editors: Duane’s foundations of clinical ophthalmology, vol 1, Philadelphia, 1994, Lippincott. "> Cook CS, Ozanics V, Jakobiec FA. (1994) Prenatal development of the eye and its adnexa. In Tasman W, Jaeger EA, editors: Duane’s foundations of clinical ophthalmology, vol 1, Philadelphia, 1994, Lippincott. </ref> The mesenchyme gives rise to the tarsal plates, levator muscles, orbicularis muscles, and tarsal muscle of Muller. <ref name=" Cook CS, Ozanics V, Jakobiec FA. (1994) Prenatal development of the eye and its adnexa. In Tasman W, Jaeger EA, editors: Duane’s foundations of clinical ophthalmology, vol 1, Philadelphia, 1994, Lippincott. "/> Eyelid formation can be first noted during week 5 when small grooves develop in the surface ectoderm (Figure 11).<ref><pubmed>7364662</pubmed></ref> These small grooves deepen and extend into the mesoderm and the primitive eyelid structures grow towards one another, eventually fusing together during week 8.<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"/> It is not until week 26-28 that the eyelids will separate again. The anterior surface of the eyelid becomes covered by two layers of epithelium; this forms the epidermis of the eyelids. <ref name="Kikkawa DO, Lucarelli MJ, Shovlin JP, et al: Ophthalmic facial anatomy and physiology. In Kaufman PL, Alm A, editors: Adler’s physiology of the eye, St Louis, 2003, Mosby, pp 16."> Kikkawa DO, Lucarelli MJ, Shovlin JP, et al: Ophthalmic facial anatomy and physiology. In Kaufman PL, Alm A, editors: Adler’s physiology of the eye, St Louis, 2003, Mosby, pp 16.</ref> Tarsal plates then begin to develop, which eventually leads to the formation of meibomian glands. <ref name="PMID1628748"/> The ectoderm reflects over the developing cornea to form the conjunctival sac, a space that is filled by secretions from the lacrimal gland in order to allow smooth motions of the eyelid over the eye and also to clean the cornea and prevent accumulation of particles on the eye that may disrupt vision. By the time the eyelids separate, the eye has all its major components present (Figure 12), and further development consists mainly of growth and vascularisation.

[[File:Formation of the eyelid 1.jpg|400px|thumb|left|Fig.11: Small grooves in the ectoderm of the head - the precursors to an eyelid.]] [[File:Formation of the eyelid 2.jpg|400px|thumb|center|Fig. 12: The eye after week 8 of development. Note however, that the eyelids remain fused until weeks 26-28.]]

===Lacrimal Glands===

There are three stages of lacrimal gland development. The first is the presumptive glandular stage in which the superior conjunctival fornix epithelium thickens and the surrounding mesenchymal cells condense. These mesenchymal cells are of neural crest origin<ref><pubmed>9882499</pubmed></ref>. The second stage sees the development of nodular formations around the superior conjunctival fornix and the formation of lumina within the epithelial buds, this stage is therefore known as the bud stage. Innervation and vascularisation also occur during this stage. The final morphological changes occur during the glandular maturity stage which occurs in weeks 9-16 when the lacrimal glands begin to resemble the mature glands. During the 13th week the lacrimal and zygomatic nerves anastomose<ref><pubmed>14635806</pubmed></ref>.

These glands are responsible for the production of tears however they do not start to function until 1-3 months after birth. The mature lacrimal gland is made up of two lobes- the palpebral and orbital lobes.

==Current Research==

Not only are there still many important processes and components of eye development that we would like to understand, this knowledge also contributes to the development of treatments for eye disorders and technologies such as the bionic eye.

===The impact of visible light on the immature retina===

<pubmed>22405869</pubmed>

The authors mentioned in this article <ref name="PMID22405869"><pubmed>22405869</pubmed></ref> that they were interested in investigating the effect of light on postnatal eye development in mice, because mice are born with fused eyelids, which separate 12 days after birth. Before the eyelids separate, the retina develops in mice with very little radiation from light. It is believed that the darkness plays a role in the development of the retina in mice, which is why their eyelids are fused for 12 days after birth. Therefore the authors were interested to see what effect light would have on postnatal retinal development of mice, with special interest in retinal ganglion cells (RGC). In their experiment, they surgically opened the eyelids on the right eyes of some of the mice to expose them to visible light 12 hours per day, while they left some other mice in the dark after surgical separation of their eyelids. They also kept the left eyes of the mice naturally fused as controls in the experiment. Their results showed that early light exposure in mice causes a decrease in retinal ganglion cells because it affects cellular apoptosis in the retina. The authors also observed that early exposure to light in mice causes lumican mRna transcription to resume and to quickly increase. (Lumican normally stays silent in retina after birth).

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===GABA Maintains the Proliferation of Progenitors and Non-Pigmented Ciliary Epithelium===

<pubmed>22590629</pubmed>

{| width=800px
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| GABA is an ‘inhibitory neurotransmitter’ in the central nervous system of adults. <ref name="PMID22590629"><pubmed>22590629</pubmed></ref> It is responsible for controlling proliferation of stem cells and progenitor cells. The authors of this article <ref name="PMID22590629"/> was interested to find the effects of GABA on proliferation of progenitor cells and non-pigmented ciliary epithelial cells (NPE) in the retina. Their study focused on progenitor cells and non-pigmented epithelium of the ciliary body in chickens. Non-pigmented epithelial cells in chickens arise from the neuroepithelium of the optic cup. They share similar functions as progenitors of the early retina, such as expression of Chx10 and Pax6 genes. It is not agreed upon whether epithelial cells of the ciliary body have stem cell properties. However, it has been found that these cells can be cultured and transplanted into retinas that are injured, in order to replace neurons that were previously lost. However, there is not much known about what factors regulate the proliferation of stem cells. Hence the authors were interested in finding the effects of GABA on proliferation of retinal cells. Their results showed that non-pigmented epithelial cells in chickens ‘express extrasynaptic-like GABAA receptors’ that have the ability to regulate cell proliferation. It has been found that inhibiting these ‘GABAA receptors’ also causes a decrease in proliferation of retinal progenitor cells and non-pigmented epithelial cells in 'the intact E8 retina’. <ref name="PMID22590629"/>

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[[File:Gaba-effects-retina.JPG|thumbnail|250px|'''GABAA receptor mediated effects on retinal progenitor cell proliferation'''
]]
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===Stem Cells===

[http://www.advancedcell.com/patients/clinical-trial-information/ Advanced Cell Technology] is a biotechnology company which is currently running two clinical trials that utilise human embryonic stem cell derived retinal pigmented epithelial cells. These trials are examining the possibility of using these cells to treat stargardt's macular dystrophy and dry age-related macular degeneration.

Despite the discovery of human embryonic stem cells (hESCs) 13 years ago, these trials are the first to describe the subretinal transplantation of hESCs into humans. The participants in these trials were sufferers of Stargardt's macular dystrophy or dry age-related macular degeneration, which is the chief cause of blindness in the developed world.

The trials were relatively successful in the sense that the hESC-derived retinal pigment epithelium cells that were implanted integrated well into the existing tissue, and there were no signs of hyperproliferation, abnormal growth, or rejection. The authors hope that in future this technique will be applied to patients in the earlier stages of disease, preventing disease progression<ref><pubmed>22281388</pubmed></ref>.

-------------------

===Bionic Eye===
[http://bionicvision.org.au/ Bionic Vision Australia] are the first organisation to implant a bionic eye. In 2012 a prototype made up of a retinal implant with 24 electrodes was implanted into 3 different patients with retinitis pigmentosa.

A camera is used to capture images which are transferred to an external data processing unit. From here the data is processed and transmitted via a wire to the implanted receiver, which in turn sends the signal to the retinal implant. The retinal implant is then able to stimulate the visual pathways in the brain.

Bionic Vision Australia hopes that in 2013, trials for a wide-view device that consists of 98 electrodes will be in progress. This prototype will be inserted into the suprachoroidal space in order to prevent mechanical damage to the retina. Trials for a more advanced high-acuity device with 1024 electrodes are planned for 2014. The electrode array contained in this device will be made of diamond to prevent irritation of surrounding tissues. These devices are expected to be suitable for patients with retinitis pigmentosa and age-related macular degeneration. The eventual goal will be to provide a completely wireless device which gives the patient high visual acuity.

[[File:Bionic_eye.jpg|right|thumb|300px|Early prototype of the bionic eye.]]

===MIP/Aquaporin 0 Represents a Direct Transcriptional Target of PITX3 in the Developing Lens===

<pubmed>21698120</pubmed>

{| width=800px
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|PITX3 plays a siginificant role in the development of lens in vertebrates. If there is a deficiency is PITX3, it causes a range of problems in humans such as microphthalmia, Peter’s anomaly, or isolated cataracts. Mutation of PITX3 also causes degeneration of the lens in zebrafish and mice. It is therefore important to understand what factors may affect the decrease in PITX3, as a normal level of PITX3 is needed to maintain normal eye development. The authors wanted to investigate specific genes which are affected by PITX3. Previous research has shown that MIP and Aquaporin causes defects in the lens in both mice and humans. MIP and Aquaporin are targeted by PITX3, so their imbalance is interrelated in the cause of defects in the lens. Therefore it has been previously proven that PITX3 is needed for normal development of the lens. However, there has not been much information previously known regarding the exact effect that PITX3 has, or the specific genes it targets. Since MIP and Aquaporin is common genes found in humans, mice and zebrafish, the authors <ref name="PMID21698120"><pubmed>21698120</pubmed></ref> chose to study these genes to understand the pathway that PITX3 takes and its exact involvement in the development of the lens. Their results proved that deficiency in MIP and Aquaporin indeed affects normal development of the lens, and it is indeed related to deficiency in PITX3. However, there is still more research needed to understand PITX3 and the genes it interacts with, and their effect in ocular development.

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[[File:Mip1-expression-in-pitx3.jpg|thumbnail|250px|'''Analysis of mip1 expression in pitx3-mo and control embryos via in situ hybridization and RT-PCR''']]
|}

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===Activation of c-Jun N-terminal kinase (JNK) during mitosis in retinal progenitor cells.===

<pubmed>22496813</pubmed>

{| width=800px
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| In the past, most studies about c-Jun N-terminal kinase (JNK) in the retina have been in relation to neurodegeneration. <ref name="PMID22496813"><pubmed>22496813</pubmed></ref> Therefore the authors in this article were interested in investigating the function of c-Jun N-terminal kinase in the retinal progenitor cells in neonatal rats. <ref name="PMID22496813"/> In the experiment, they took retinal tissue from newborn rats and fixed them, and subsequently examined them using confocal microscopy and fluorescence to discover c-Jun N-terminal kinase ‘phosphorylation by immunohistochemistry’. <ref name="PMID22496813"/> Mitotic cells in the retina were identified during the experiment. The results of their experiment revealed that c-Jun N-terminal kinase is phosphorylated in the developing retina of neonatal rats during the mitosis of progenitor cells. <ref name="PMID22496813"/> This shows that c-Jun N-terminal kinase can control the proliferation of progenitor cells in the developing retina. Their experiment also revealed that inhibiting c-Jun N-terminal kinase causes disruptions to the mitotic cell cycle by reducing the cell numbers in anaphase. <ref name="PMID22496813"/> However, inhibiting c-Jun N-terminal kinase did not change the cell numbers in metaphase or prophase. <ref name="PMID22496813"/>

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[[File:JNK1.png|thumbnail|300px|'''"JNK is phosphorylated during mitosis of retinal progenitor cells."''']]
|}

----------------------------

===LRP5 is required for vascular development in deeper layers of the retina===

<pubmed>20652025</pubmed>

{| width=800px
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The lipoprotein receptor-related protein 5 (LRP5) has a significant function in the development of retinal vasculature.<ref name="PMID20652025"><pubmed>20652025</pubmed></ref> Research has shown that mutations of the LRP5 causes loss of function, due to incomplete development of retinal vessel network, in both humans and mice. The authors investigated how mutations occur in the LRP5, which leads to abnormal development of the retinal vasculature. They have studied retinal endothelial cells in mutant mice in their study. Their results showed that in retina with mutated LRP5, endothelial cells in the retinal vasculature primarily produced cell clusters in the inner-plexiform layer instead of migrating into deeper layers of the retina to form normal retinal vasculature. The authors also discovered that there was a decrease in Slc38a5, which is “a Müller cell-specific glutamine transporter”, in mice with mutated LRP5. Their results lead the authors to conclude that normal LRP5 is very important in the development of normal retinal vasculature due to their role in causing migration of retinal endothelial cells in the deeper layers of the retina. LRP5 is also important for retinal interneurons and Müller cells to function correctly.

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[[File:Retina-cell-clusters.JPG|350px|thumbnail|'''Endothelial cells form thick clusters in the LRP5 mutant retina''']]
|}

-----------------

===Astrocyte-Derived Vascular Endothelial Growth Factor===

<pubmed>20686684</pubmed>

{| width=800px
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Vascular endothelial growth factor (VEGF) has an important role in normal development of retinal vasculature. <ref name="PMID20686684"><pubmed>20686684</pubmed></ref> In the process of vascularisation of the retina, the retinal astrocytes (both vascularised and not yet vascularised) expresses the vascular endothelial growth factor. <ref name="PMID20686684"/> This fact indicates that vascular endothelial growth factor that are derived from astrocytes of the retina plays an important role in vessel maturation and angiogenesis. <ref name="PMID20686684"/> Therefore the authors wanted to test the role of vascular endothelial growth factor that are derived from astrocytes to find further confirmation. ‘Cre-lox technology’ was used in the experiment to remove the vascular endothelial growth factor from mice retinal astrocytes in the developmental period. <ref name="PMID20686684"/> The results showed that removing vascular endothelial growth factor that are derived from astrocytes caused ‘the regression of smooth muscle cell-coated radial arteries and veins’ from the effects of hyperoxia. <ref name="PMID20686684"/> Hence, this result indicates that vascular endothelial growth factor plays an important role in stabilising blood vessels during the development of the retinal vasculature. <ref name="PMID20686684"/> It has been suggested that this finding may be of relevance to retinopathy in premature neonatal humans. <ref name="PMID20686684"/>

[[File:Astrocyte-vegf-deletion.JPG|250px|thumbnail|'''"Astrocyte specific deletion of VEGF." ''']]
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[[File:Effect-of-vegf-on-retinal-vasculature.JPG|250px|thumbnail|'''"Effects of astrocyte-derived VEGF on retinal vascular development."''']]
[[File:Vegf-protects-vessels.JPG|250px|thumbnail|'''Astrocyte-derived VEGF protects vessels from hyperoxia. ''']]

|}

==Useful Links==

{{External Links}}

[http://www.youtube.com/watch?v=Xme8PA6xv-M Visualisation of eye development in the embryo]

[http://www.youtube.com/watch?v=wJE6pYwAMVU Brief Video on Embryonic development of the eyes]

[http://www.embryo.chronolab.com/sense.htm Embryonic Development of the eye]

[http://webvision.med.utah.edu/book/ Webvision free online textbook]

[http://www.ophthobook.com/chapters/ Free basic online book about the eyes]

[http://www.youtube.com/watch?v=deEjbVdnwyA&feature=related Anatomy of the Eyes- Video]

[http://www.vetmed.vt.edu/education/curriculum/vm8054/eye/EMBYEYE.HTM Simple eye embryology explanation]

==Glossary==

'''Accommodation''' - changing the focal length of the lens in order to focus on an object.

'''Anterior chamber''' - Fluid-filled area located between the iris and cornea.

'''Choroid''' - The middle coat of the eye, located between the sclera and retina, which contains blood vessels that nourish the structures in the eye.

'''Ciliary body''' - Structure located behind the iris which secretes aqueous humour. It contains ciliary muscle, which is involved with changing the shape of the lens for accommodation.

'''Cornea'''- a transparent section in the anterior of the eye which acts as a window over the pupils, and is involved with refracting light as it enters the eye.

'''Downstream genes''' - genes that are activated by other "upstream genes".

'''Ectoderm''' - outermost layer of germ cells in an early embryo.

'''Endoderm''' - innermost layer of germ cells in an early embryo.

'''Extraocular muscles''' - Muscles that control the movement of the eyeball.

'''Glial cells''' - non-neuronal cells that provide structure and protection to neurons as well as producing myelin.

'''Inductive signaling''' - a process whereby the secretion of factors from one cell or tissue triggers a response in another.

'''Iris'''- A circular shaped muscle which controls the opening and contraction of the pupil.

'''Lens'''- A structure inside the eye which refracts light as it enters the eye for clear vision.

'''Lens vesicle''' - the cavity of invaginated ectoderm from the optic placode that will form the lens.

'''Macula''' - a highly pigmented, oval-shaped area located near the centre of the retina. Important for visual acuity.

'''Mesenchyme''' - undifferentiated, loose connective tissue.

'''Mesoderm''' - middle layer of germ cells in an early embryo.

'''Mesothelium''' - the epithelial layer of the mesoderm.

'''Myelinisation''' - development of a myelin sheath around a nerve fibre.

'''Neural crest''' - a portion of the ectoderm situated next to the neural tube.

'''Neural groove''' - a large invagination on the dorsal surface of the embryo which will close off and form the neural tube.

'''Neural tube''' - hollow structure that results from the folding of the neural plate and eventually forms the central nervous system.

'''Neuroblastic layer''' - a layer of immature cells that differentiate to form either glial cells or neurons. The retina has two of these (an inner and outer).

'''Neuroectoderm''' - portion of the ectoderm that develops to form the central and peripheral nervous systems.

'''Optic chiasm''' - the point at which the optic nerves meet and cross over.

'''Optic cup''' - the structure that is formed after the optic vesicle folds in upon itself. This will form the retina.

'''Optic globe''' - a term that refers to the optic cup, lens vesicle and surrounding mesenchyme collectively.

'''Optic Nerve''' - The nerve which carries visual information from the retina to the brain for processing.

'''Optic placode''' - area of thickened ectoderm that gives rise to the lens of the eye.

'''Optic stalk''' - a long, narrow cavity that will produce the optic nerve.

'''Optic vesicle''' - a cavity that buds off from the neural tube and gives rise to the optic cup.

'''Posterior chamber'''- Fluid-filled area located between the iris and lens.

'''Pupil'''- opening in the anterior part of the eye, which controls how much light enters the eye.

'''Retina''' - Light-Sensitive portion located towards the back of the internal surface of the eye, which contains photoreceptors (rods and cones) which detects visual information and transmits it to the brain through the optic nerve.

'''Sclera'''- white part of the external anterior surface of the eye, which envelopes the eyeball to give it support and protection of its internal contents.

'''Upstream genes''' - genes that activate one or more other "downstream genes".

'''Vascularise''' - to invade with blood vessels.

'''Vitreous Chamber'''- Area located between the lens and retina, which contains vitreous (a jelly like substance) whose function is to maintain the shape of the eye.

==Image Gallery==
<gallery>
Image:Eye_diagram_bandw.jpg‎ | Basic structure of the human eye.
Image:Eyediagramcolour1.JPG | Basic anatomy of the eye.
Image:Stage14 sem2b-limb.jpg | A Stage 14 embryo showing the location of an otic placode.
Image:Stage 13 image 060.jpg | A cross section showing the organisation of the developing brain, the optic vesicle and the lens (optic) placode.
Image:Formation of the optic vesicle 1.jpg | Early formation of the optic vesicle from the neural groove.
Image:Formation of the optic vesicle 2.jpg | The optic vesicle at a later stage, showing the optic stalk.
Image:Formation of the optic nerve and chiasm 1.jpg | A recognisable brain and eye structure in later development.
Image:Formation of the optic cup 1.jpg | Mechanism of optic cup formation.
Image:Formation of the optic cup 2.jpg | Layers of the optic cup in retina development.
Image:Formation of the retina 1.jpg | Cross-section of the primitive retina showing cell types and layers.
Image:Formation of the retina 2.jpg | Cross-section of a developed retina showing cell types and layers.
Image:Formation of the lens 1.jpg | The importance of the optic cup in lens differentiation.
Image:Formation of the lens 2.jpg | The lens placode separates from the ectoderm and migrates into the mesoderm forming the lens vesicle.
Image:Formation of the choroid and sclera 1.jpg | The choroid and sclera derives from mesenchyme surrounding the optic cup.
Image:Formation of the eyelid 1.jpg | Small grooves in the ectoderm of the head - the precursors to an eyelid.
Image:Formation of the eyelid 2.jpg | The eye at an advanced stage of embryonic development. Note however, that the eyelids remain fused until much later.

</gallery>

==References==
<references/>

----

--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

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{{2012Projects}}

File:Bionic eye.JPG

2012-10-03T01:20:30Z

Z3254758: Early prototype of the bionic eye. Photo courtesy of Study in Australia.gov Copyright Notice © Commonwealth of Australia 2011 This work is copyright. You may download, display, print and reproduce this material in unaltered form only (retaining this

Early prototype of the bionic eye.

Photo courtesy of Study in Australia.gov

Copyright Notice

© Commonwealth of Australia 2011

This work is copyright. You may download, display, print and reproduce this material in unaltered form only (retaining this notice) for your personal, non-commercial use or use within your organisation. Apart from any use as permitted under the Copyright Act 1968, all other rights are reserved. Requests and inquiries concerning reproduction and rights should be addressed to Commonwealth Copyright Administration, Attorney General’s Department, National Circuit, Barton ACT 2600 or posted at http://www.ag.gov.au/cca

Any comments or queries should be sent to: webmaster@studyinaustralia.gov.au

2012 Group Project 1

2012-10-03T00:32:24Z

Z3254758: /* Stem Cells */

[[File:Eye_collage_2.jpg|right|830px]]

=Vision Development=

==Introduction==

Eyes are an important sensory organ shared across many different species and allow organisms to gather useful visual information from their environment. The visual system uses light from the environment and processes this information in the brain for visual perception. The visual system is complex, and is made up of various structures that work together to form vision. Each of the structures in the eye have specific tasks which contribute to the visual system. Knowledge of how the eye develops extends as far back as Aristotle more than 2000 years ago, and current knowledge shows that most of the crucial events of eye development occur in the embryological stage. The eye is an interesting model for studying the development of tissues in organisms, as it consists of cells from several parts of the embryo including the head ectoderm, neural ectoderm and mesoderm. From its many origins the cells come together and differentiate to produce the complex organ that is the eye. During this period there are many examples of inductive signaling, as the tissues coordinate their development throughout this elegant process.

The main anatomical structures of the eye are as follows:
{|
|
* Cornea

* Sclera

* Choroid

* Iris

* Ciliary body

* Lens

* Anterior chamber

* Posterior chamber

* Retina

* Optic nerve

|[[File:eye_diagram_bandw.jpg|right|250px|thumb|Basic structure of the human eye.]]
|}
[[File:Eyediagramcolour1.JPG|550px]]

==Research History==

=== '''Brief Timeline of Historical Developments on the Eye and its Embryology''' ===

{| width=800px
|-bgcolor="CEDFF2"
| width=100px|'''Time'''
| width=700px|'''Discovery'''

|-bgcolor="F5FAFF"
| '''Ancient Egyptians'''
| First to document cataracts. It is described as being 'the white disease of the eye' or 'darkening of the pupil.' <ref>Edwards, D.D. (1996). Ophthalmology before Hippocrates. In the History of Ophthalmology, ed. D.M. Albert and D.D. Edwards. Cambridge, Mass.: Blackwell Science.</ref> The Egyptians had some knowledge of the eye, however it is not known how much of the anatomy of the eye was known in their era.

|-bgcolor="CEDFF2"
| '''535 BC'''

|
Ancient Greek philosopher Alcmaeon conducted dissection of humans for the first time in recorded history. This included dissection of the eye. However, not much is known about which anatomical features he discovered. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17.">Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17.</ref>

|-bgcolor="F5FAFF"
| '''384- 322 BC'''

| [[File:Aristotle-eye.jpg|200px|thumbnail|The eye according to Aristotle.<ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "> Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau </ref> Note the lens is missing, and there are three vessels drawn that was believed to transport fluid to and from the eye.<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
]]
Aristotle performed dissections of animal embryos.<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

When Aristotle described the embryo of a ten day old chicken, he wrote "The eyes about this time, if taken out, are larger than beans and black; if their skin is removed the fluid inside is white and cold, shining brightly in the light, but nothing solid." <ref name="Magnus, H. (1998). Ophthalmology of the ancients. In J. Hirschberg (Ed.), The History of Ophthalmology: The monographs, Vol. 4, Part 1 (F.C. Blodi, Trans.) Bonn: Wayenborgh.">Magnus, H. (1998). Ophthalmology of the ancients. In J. Hirschberg (Ed.), The History of Ophthalmology: The monographs, Vol. 4, Part 1 (F.C. Blodi, Trans.) Bonn: Wayenborgh.</ref>

Aristotle believed that the eyes started forming during early embryogenesis, however, he also believed that the eyes are the last organs to form completely, and he incorrectly thought that the eyes shrink in later embryonic development. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press.">Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press.</ref> .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"

| '''340 BC'''

| Lens is thought to have been discovered by Hippocrates, due to his descriptions of the contents of the internal eye There has been studies in chick development later on by followers of Hippocrates. They claimed that eyes were visible in early embryogenesis. .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
|-bgcolor="F5FAFF"
|'''25 BC - 50 AD'''

| [[File:Celsus-eye.jpg|150px|thumb|The eye according to Celsus. <ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "/>
Note the lens is placed in the centre of the eye, in the vitreous.<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> ]]

Aulus Cornelius Celsus wrote a Roman medical text called 'De Medicina' in which he wrote that the lens was the part of the eye from which vision originated. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.">Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.</ref> Celsus also incorrectly drew the lens in the center of the globe in his diagram of the eye. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

|-bgcolor="CEDFF2"
| '''23-79 AD '''
|
Pliny the Elder said that the eye is the last of the organs to develop in the womb <ref name="Magnus, H. (1998). Ophthalmology of the ancients. In J. Hirschberg (Ed.), The History of Ophthalmology: The monographs, Vol. 4, Part 1 (F.C. Blodi, Trans.) Bonn: Wayenborgh."/>
|-bgcolor="F5FAFF"
| '''98-117 AD'''

| [[File:Rufus-eye.jpg|150px|thumb|The eye according to Rufus of Ephesus. <ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "/>
Note the lens is placed in the correct position, behind the iris of the eye <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> ]]

Rufus of Ephesus identified the lens as being located in the anterior part of the eye, close to the pupil. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

His diagram illustrates that he knew the correct position of the lens as being directly behind the iris, in the anterior part of the eye, and not in the centre as was previously depicted by others before him.

|-bgcolor="CEDFF2"
| '''130-200 AD'''

| [[File:Galen-eye1.jpg|150px|thumb|The eye according to Galen. <ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "/> ]]

Claudius Galen practised medicine in Rome. He wrote:

"1. Within the eye the principal orgran of sensation is the crystalline lens.

2. The sensation potential comes from the brain and is conducted via the optic nerves.

3. All other parts of the eyeball are supporting structures." <ref> Hirschberge, J. (1982). Antiquity, Vol. X in the History of Ophthalmology (F.C. Blodi, Trans.) Bonn: Wayenborgh. pp. 280 </ref>

Galen thought that the lens was produced from the vitreous. He also believed that the retina’s function was to give nourishment to the lens and vitreous, and to carry visual information to the brain from the lens. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

|-bgcolor="F5FAFF"

| '''1514-1564'''

| Andreas Vesalius published his anatomy book "De Humani Corporis Fabrica in 1543. He had the misconception that the lens was located in the centre of the eyeball. .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> He also wrote that the lens functioned "like a convex lens made of glass" <ref name="Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.">Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.</ref> pp. 48
|-bgcolor="CEDFF2"
| '''1535-1606'''

| Georg Bartisch correctly drew a diagram of the lens placed behind the iris in his book 'Ophthalmodouleia: das ist Augendienst'. <ref name="Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>
|-bgcolor="F5FAFF"

| '''1537-1619'''

| Fallopio Hieronymus Fabricius ab Aquapendente studied anatomy and embryology. He studied chicken embryos, and thought that chalazae (which comes from egg white) gives rise to the eyes. He also drew the lens directly behind the iris in a diagram in is book 'Tractatus de Oculo Visuque Organo. <ref name="Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

|-bgcolor="CEDFF2"
| '''1583'''

| Felix Platter published his book 'De corporis Humani Structura et Usu, after he performed dissections of human bodies. He believed that the retina is the primary visual organ in the eye. .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="F5FAFF"
| '''1619'''
| Scheiner is given credit to be the first person to correctly draw the diagram of the anatomy of the eye. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
|-bgcolor="CEDFF2"
| '''1672'''
| Marcello Malpighi described the embryonic development of the chicken. He drew many detailed diagrams of the chick eye. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1665'''
| Nicolaus Steno identified the choroid fissure in his study of a developing embryo of a chicken. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="CEDFF2"
| '''1754'''

| Albrecht von Haller studied the embryology of the eye. With help from his student Johann Gottfried Zinn, he contributed to the understanding of the development of the ciliary body, ciliary zonule, and their relationship with the lens and vitreous. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1817'''

| Christian Pander discovered the three embryonic germ layers, which he wrote about in his book. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/> Pander was the first to think of 'the optic vesicles as lateral evaginations' of the 'prosencephalon'; however, he was incorrect about the details regarding how 'the eye develops from these evaginations'. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="CEDFF2"
| '''1828-1837'''

| Karl Ernst von Baer studied embryology. He discovered that the optic vesicles were 'outgrowths of the embryonic forebrain' <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> which he believed was caused by pressure from fluids in the central nervous system. Von Baer also believed that the optic vesicle opens to form the pupil, and that fluid in the optic vesicle coagulates to form the vitreous body and lens. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1830'''

| Emil Huschke discovered that the lens forms from the invagination of the surface ectoderm. He concluded that the lens hence does not form ‘from the fluid of the optic vesicle’ <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> as previously thought.
|-bgcolor="CEDFF2"
| '''1832'''

| Emil Huschke wrote in his manuscript ‘Ueber die erste Entwinkenlung des Auges und die damit zusammenhängende Cyklopie’ that the lens capsule forms from the outer surface ectoderm, which detaches and moves back inward, which is later enclosed again by several membranes, such as by the cornea. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

Huschke also described how the optic cup and choroid fissure forms. He discovered that the optic vesicles are produced from the two-layered optic cup. However, he incorrectly described the destiny of the ‘individual optic cup layers’. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

|-bgcolor="F5FAFF"
| '''1838'''
| Matthias Jakob Schleiden and Theodor Schwann formulated the ‘cell theory’: “All living things are formed from cells, the cell is the smallest unit of life, and cells arise from pre-existing cells.” <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
|-bgcolor="CEDFF2"
| '''1839'''

| Theodor Schwann contributed a better understanding of the development of the lens through studying the foetus of a pig, which he wrote about in his book ‘Mikroskopische Untersuchungen Über Die Uebereinstimmung in Der Struktur Und Dem Wachsthum Der Thiere Und Pflanzen’. He wrote that the lens is made of ‘concentric layers’ of fibres which proceeds from an anterior to posterior direction. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1842'''
| Robert Remak gave the current names to the three embryonic germ layers: ectoderm, mesoderm and endoderm. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"
| '''1843'''
| Wilhelm Werneck published his book ‘Beiträge zur Gewebelehre des Kristallkörpers’. He wrote that the contents inside of the lens is not made of fluids, as was previously believed. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/> Werneck also discovered that the fibers of the lens continues to grow from the outside to the centre during embryogenesis. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

|-bgcolor="F5FAFF"
| '''1855'''

| Robert Remak wrote his book ‘Untersuchungen über die Entwickelung der Wirbelthiere’. He wrote about what he discovered in his studies of the development of the eye in the embryos of chickens, frogs, and rabbits. He wrote very descriptively about the embryology of lens formation, amongst other topics. He discovered that the ectoderm gives rise to the lens placode. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

|-bgcolor="CEDFF2"
| '''1858'''
| Henry Gray published his book 'Anatomy, Descriptive and Surgical'. He had also previously studied the embryonic development of the optic nerve and retina of chickens.
|-bgcolor="F5FAFF"
| '''1877'''
| Paul Leonhard Kessler wrote about the embryonic development of the lens in mice in his book ‘Zur Entwickelung des Auges der Wirbelthiere. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"
| '''1891'''
| Vincenzo Colucci studied newts and discovered their ability to regenerate the lens.<ref> Tsonis, P. A. (2001). Regeneration of the Vertebrate Lens and Other Eye Structures. eLS. (Online Publication). DOI: 10.1038/npg.els.0001102 </ref>
|-bgcolor="F5FAFF"
| '''1892'''
| Dr. Oscar Hertwig published his book ‘Text-Book of the Embryology of Man and Mammals. <ref> Hertwig, O. Text-book of the embryology of man and mammals. S. Sonnenschein 1901. (Translated from the 3d German ed. by Edward L. Mark.) </ref> It contains a very detailed description of the development of the eye, according to the findings at that time. [http://embryology.med.unsw.edu.au/embryology/index.php?title=Book_-_Text-Book_of_the_Embryology_of_Man_and_Mammals_16-2#The_Development_of_the_Eye]
|-bgcolor="CEDFF2"
| '''1895'''
| Gustav Wolff also independently studied newts and discovered their ability to regenerate the lens. .<ref> Tsonis, P. A. (2001). Regeneration of the Vertebrate Lens and Other Eye Structures. eLS. (Online Publication). DOI: 10.1038/npg.els.0001102 </ref>

|-bgcolor="F5FAFF"

| '''1900'''
| Carl Rabl published his book ‘Uber den Bau und die Entwicklung der Linse’. He wrote about the development of the lens in mammals, fish, birds, reptiles, and amphibians. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"
| '''1901'''
| Hans Spemann published his findings from his experimental studies about the formation of the lens in the frog. He found that the optic cup needed to be in contact with the ectoderm for normal development of the eye. <ref> Spemann, H. (1901). Über Correlationen in der Entwicklung des Auges. Verhand. Anat. Ges. 15: 61-79. </ref> <ref> Saha, M. (1991). Spemann seen through a lens. In Gilbert, S. F. (ed.). A Conceptual History of Modern Embryology. Plenum Press, NY. pp. 91-108.</ref>
|-bgcolor="F5FAFF"
| '''1906'''
| Brown ‘s book “The Embryology Anatomy and Histology of the Eye” was published. It contained detailed descriptions of the embryonic development of the eye according to the knowledge current at that time, mainly based on observations from embryos of rabbits and chickens. <ref> Brown, E.J. (1906). The Embryology Anatomy and Histology of the Eye. Chicago: Hazlitt & Walker. 1906 </ref>

|-bgcolor="CEDFF2"
| '''1907'''

| John Clement Heisler published his book ‘A Text-book of embryology’. It contains a chapter detailing the embryonic development of the eye, according to the knowledge current at that time. The book’s copyright has expired, so it can be viewed free online: [http://archive.org/details/atextbookembryo01heisgoog]

Julius Kollman also published his book 'Atlas of the Development of Man'. It contained very detailed description and illustrations showing the embryonic development of the human according to the knowledge current at that time. His illustrations were reused by many others after his time and built upon for further refined understanding of the embryology of the human.

Here are examples of Julius Kollman's excellent illustrations showing eye development in various stages:

'''Formation of Primary Optic Vesicle:'''
<gallery>
File:Kollmann691.jpg|The blue part at the bottom is the endoderm. The pink middle layer is the mesoderm. The top yellow layer is the ectoderm. The fold labelled as 'augenfeld' is the place where the optic vesicle will form.
File:Kollmann692.jpg|The eye area (augenfeld) is a bowl shaped bulge still located on the side walls.
File:Kollmann693.jpg| The neural tube is shown after removal of all of the ectoderm and ventral organs, such as heart, gut tube, etc. The primary optic vesicle forms a slightly flattened hollow protrusion on the forebrain.
File:Kollmann694.jpg|The lateral surface of the primary optic vesicle is slightly depressed, showing the first sign of the emergence of the secondary optic vesicle
</gallery>

'''Development of Lens:'''

<gallery>
File:Kollmann695.jpg|The bulging lateral wall of the primary optic vesicle is covered by a fairly well demarcated lens plate, a direct continuation of the ectoderm. Between the optic vesicle and the lens pit are some flattened spindle-shaped cells. In the adjoining mesoderm are cross-sections of capillaries.
File:Kollmann697.jpg|The lens still hangs together with the ectoderm. The primary eye vesicle is indented with respect to the lens. Between the lens and the lateral plate of the optic vesicle is a narrow space, which allows area to further develop later.
File:Kollmann698.jpg|4th Week of development. The internal organisation shows the secondary optic vesicle. A: The rear wall of lens is noticeable and is enveloped by mesoderm. B: The edges of the lens pit is already grown and the lens vesicles are formed, which is still related to the remaining ectoderm.
File:Kollmann699.jpg|The lens has now cut off from the ectoderm, but is still very superficial. Between it and the lateral lamina of the optic cup, there is a considerable space. The eye stalk has become longer and is enclosed together with the optic cup and lens of the mesoderm. The cornea, sclera and choroid make gradual development.
</gallery>

|-bgcolor="F5FAFF"

| '''1921'''
| Bailey and Miller published their textbook “Text-Book of Embryology “. <ref> Bailey, F.R. and Miller, A.M. (1921). Text-Book of Embryology. New York: William Wood and Co. (Note- This book is only at an early edited stage)</ref> It contains detailed description of the development of the embryonic eye according to the knowledge current at that time. [http://embryology.med.unsw.edu.au/embryology/index.php?title=Book_-_Text-Book_of_Embryology_18]

|-bgcolor="CEDFF2"
| '''1925'''

| Mann published his research article, in which he gives a detailed account of the development of the human iris. He divided the development of the iris into four stages: weeks 4-7 (before the ectodermal iris forms or before the anterior chamber forms); weeks 7-11 (anterior chamber appears, and mesodermal iris forms); weeks 11-12 (ectodermal iris forms); 3-8 months (muscles of the pupil forms from ectodermal iris, and the central portion of the mesodermal iris atrophies to make the pupil clear). <ref name="PMID18168466"><pubmed>18168466</pubmed></ref>
O Leser also published an article detailing the development of extraocular muscles in mammals he studied. <ref name="PMID18168498"><pubmed>18168498</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1939'''
| Holtfreter <ref> Holtfreter, J. (1939). Gewebeaffinitat, ein Mittel der embryonalen
Formbildung. Arch. Exp. Zellforsch. 23, 169-209. </ref> studied amphibians and observed that that the development of the eye stops at the ‘optic vesicle stage’ if there is no contact ‘with the epidermis and neural crest driven mesenchyme’. <ref name=”PMID11023863”><pubmed>11023863</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1955'''
| Barber published his book ‘Embryology of the human eye’. <ref> Barber AN: Embryology of the human eye. St. Louis. CV Mosby 1955</ref> In contains detailed descriptions of the embryological development of the human eye according to the knowledge current at that time. It contains many photographs of the eye at different stages of development.

|-bgcolor="F5FAFF"
| '''1957'''
| Coulombre studied a chicken embryo to find the role of intraocular pressure in the development of the chick’s eye, especially in regards to its control of the size of the eye structures. <ref name="PMID13469954"><pubmed>13469954</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1958'''
| Coulombre studied the development of the cornea and how it develops its transparency. <ref name="PMID13563560"><pubmed>13563560</pubmed></ref> He also studied the development of corneal curvature. <ref name="PMID 13519969"><pubmed> 13519969</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1962'''
| Coulombre studied the development of the conjunctival papillae and scleral ossicles. <ref name="PMID 14023393"><pubmed> 14023393</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1963'''
| Coulombre studied the development of lens fibers and their orientation. <ref name="PMID14077035"><pubmed>14077035</pubmed></ref> He also studied the development of pigmented epithelium. <ref name="PMID14023394"><pubmed>14023394</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1964'''

| Coulombre further studied the development of the lens to determine the role of the lens in eye growth. <ref name="PMID14189921"><pubmed>14189921</pubmed></ref> He also studied the role of thyroid in the development of the cornea and the development of corneal transparency. <ref name="PMID14211912"><pubmed>14211912</pubmed></ref> Mann also published his work called ‘The development of the human eye’, which contains detailed description of the embryonic development of the eye according to current knowledge at that time. <ref> Mann I. The development of the human eye. New York: Grune and Stratton 1964</ref>

|-bgcolor="CEDFF2"
| '''1965'''
| Coulombre published his findings regarding the regeneration of the neural retina from pigmented epithelium in the embryo of chickens. <ref name="PMID5833111"><pubmed>5833111</pubmed></ref> Smelser also published his findings on the embryological development and morphology of the lens. <ref name="PMID14340157"><pubmed>14340157</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1966'''

| Formation of the face and orbit occurs from the differentiation of neural crest cells. <ref name="PMID5969670"><pubmed>5969670</pubmed></ref> O’Rahilly also published findings of the development of the eye in the early stages of human embryos. <ref> O'Rahilly, R. 1966 The early development of the eye in staged human embryos. Contr. Embry. Carnegie Inst., Wash., 38: 1–42</ref>

|-bgcolor="CEDFF2"
| '''1968'''
| Findings of the postnatal development of the retina of rats was published. <ref name="PMID5640327"><pubmed>5640327</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1969'''

| Mann again published his work called ‘The development of the human eye’. He stated that that the lens in humans forms completely from the ectoderm. <ref name=”Mann I. The Development of the Human Eye. New York, USA: Grune & Stratton, Inc; 1969”> Mann I. The Development of the Human Eye. New York, USA: Grune & Stratton, Inc; 1969</ref> Coulombre also studied the development of the lens, and took note of its size, shape and orientation throughout its developmental stages. <ref name="PMID 5772716"><pubmed> 5772716</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1970'''
| Coulombre again further studied the regeneration of the neural retina from pigmented epithelium of embryos of chickens. <ref name="PMID 5472476"><pubmed> 5472476</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1971'''

| Coulombre further studied the development of the lens. This time he focused on analysing the histological mechanisms in the reconstitution of the lens from implanted lens epithelium. <ref name="PMID 4925671"><pubmed> 4925671</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1973'''
| A research article was published, detailing the embryonic development of the retina of humans. <ref name="PMID 6650859"><pubmed> 6650859</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1976'''

| Geeraets published his observations of the closure of the embryonic optic fissure in golden hamsters, using the electron microscope. <ref name="PMID 1266776"><pubmed> 1266776</pubmed></ref> Kornneef also published an article based on his studies of the development of connective tissue in the human orbit. <ref name="PMID 1020699"><pubmed> 1020699</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1981'''
| A research article was published detailing how myelin forms in the optic nerve of humans. <ref name="PMID 7224936"><pubmed> 7224936</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1983'''
| O’Rahilly’s further research developments was published, reporting the timing and sequence of events in the development of the embryonic human eye. <ref name="PMID 6650859"><pubmed> 6650859</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1990'''

| Van Driell et al. <ref>Driell, D. Van; Provis, J.M.; Billson, F.A.: Early differentiation of ganglion, amacrine, bipolar and Muller cells in the developing fovea of the human retina. J. Comp. Neurol. 291: 203-219.</ref> studied the manner in which amacrine, bipolar, retinal ganglion cells, and Muller cells differentiate in the developing fovea of the retina of a 15-week old human foetus. <ref name="PMID1628748"><pubmed>1628748</pubmed></ref> Tripathy also published an article providing evidence that the lacrimal glands in humans originates from the neuroectoderm. <ref name="PMID2406219"><pubmed>2406219</pubmed></ref>

|}

==Development, Structure and Function of Ocular Components==

The eye itself is formed from several components; notably the optic placode of the head ectoderm, the optic vesicle from the neural tube, and mesenchyme from the mesoderm and neural crest cells. The optic placode contributes the lens to the eye, the optic vesicle gives rise to layers of the retina, while the mesenchyme will produce the ciliary body, iris, choroid and sclera.<ref>http://www.vetmed.vt.edu/education/curriculum/vm8054/eye/EMBYEYE.HTM</ref> Cells from the neural tube will also produce the optic nerve, which receives nerve impulses from the retina of the eye. Eyes initially form as laterally paired structures and migrate medially in the human embryo. In other animals such as birds and lizards, the eyes do not migrate and develop laterally on the head. The optic placodes become prominent on the surface of the embryo at approximately Stage 14 of development.

[[File:Stage14 sem2b-limb.jpg|200px|thumb|left|A Stage 14 embryo showing the location of an otic placode.<ref name="http://embryology.med.unsw.edu.au/embryology/index.php?title=ANAT2341_Lab_6_-_Early_Embryo">http://embryology.med.unsw.edu.au/embryology/index.php?title=ANAT2341_Lab_6_-_Early_Embryo</ref>]] [[File:Stage 13 image 060.jpg|400px|thumb|center|A cross section showing the organisation of the developing brain, the optic vesicle and the lens (optic) placode.<ref name="http://embryology.med.unsw.edu.au/embryology/index.php?title=ANAT2341_Lab_6_-_Early_Embryo"/>]]

===Optic Nerve===

The optic nerve consists of nerve fibres that transmit information from the retinal photoreceptor cells to the brain. The optic nerve is formed from the optic stalk, which develops as the optic vesicle migrates from its origin in the neural tube to its destination - the surface ectoderm - where it will fuse with the optic placode (also known as the lens placode, which will contribute the lens to the eye).<ref name="PMID11687490"><pubmed>11687490</pubmed></ref>

[[File:Formation of the optic vesicle 1.jpg|400px|thumb|left|Fig. 1: Early formation of the optic vesicle from the neural groove.]] [[File:Formation of the optic vesicle 2.jpg|400px|thumb|center|Fig. 2: The optic vesicle at a later stage, showing the optic stalk.]]

As can be seen in Figure 1 above, the optic vesicle forms from the neural tube. However, note that the neural tube has not yet closed, and is still the neural groove at this point. Figure 2 then shows the optic vesicle at slightly later stage in the same simplified cross-section of the embryo, as it migrates from the neural tube to the surface ectoderm. Note the presence of the optic stalk which links the optic vesicle to the neural tube. Later in development, this primitive structure will become the optic nerve, which will link the eye to the brain.

The nerve fibres themselves will initially originate from the retinal ganglion cells in the eye during week 6.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008">Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008</ref> After two weeks, these fibers will have grown along the inner wall of the optic stalk and have reached the brain. They grow both in length and width, with the nerve fibres filling the hollow optic stalk to form the solid optic nerve. More than one million nerve fibers will eventually make up the optic nerve, along with glial cells which arise from the inner wall of the optic stalk itself.<ref><pubmed>1451666</pubmed></ref> Myelinisation of the optic nerve begins much later in development at around 7 months, beginning at the optic chiasm and moving towards the eye.<ref><pubmed>7224936</pubmed></ref> The optic chiasm forms just before the nerves reach the brain, and is where half the nerve fibres from each eye will cross over to the opposite side of the brain. This is demonstrated in Figure 3. Note the crossing over of the optic nerves just before they enter the brain, at the optic chiasm. This organisation is now much more familiar, with the eyes near the ectoderm and the optic nerve leading through the mesoderm to the brain buried deep in the embryo.

[[File:Formation of the optic nerve and chiasm 1.jpg|400px|thumb|center|Fig. 3: A recognisable brain and eye structure in later development.]]

===Retina===

The retinal component of the eye is formed when the optic vesicle folds in upon itself, forming the optic cup (see Figure 4). In doing so it creates two layers - an inner wall and an outer wall of the optic cup (Figure 5). These two layers of the optic cup will give rise to the two layers of the retina - the inner neural retina, and the outer pigmented epithelium.<ref name="PMID11687490"/> Note the existence of the space between the two layers of the retina. This is known as the intraretinal space and disappears by the 7th week of development, however the two layers never completely fuse and can become separated as a result of physical trauma to the head - leading to a detached retina and loss of vision.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/>

The inner wall of the optic cup, which will give rise to the neural retina, consists of a layer of pseudostratified cells (see Figure 6) that later differentiate into rod, cone, bipolar, ganglion, horizontal, amacrine and glial cells of the retina (Figure 7).<ref name="PMID18168748"><pubmed>18168748</pubmed></ref> The outer wall of the optic cup consists of a layer of cuboidal cells that contain melanin - the light absorbing pigment. The function of this layer is to absorb light and prevent internal reflection of light within the eye, which would impair our ability to form distinct images. Interestingly, in some animals such as cats, this layer actually reflects light intentionally to increase the amount of light available to the eye in low-light conditions. This is why cats seem to have eyes that glow in the dark.<ref>http://dialspace.dial.pipex.com/agarman/bco/fact4.htm</ref>

[[File:Formation of the optic cup 1.jpg|400px|thumb|left|Fig. 4: Mechanism of optic cup formation.]] [[File:Formation of the optic cup 2.jpg|400px|thumb|center|Fig. 5: Layers of the optic cup in retina development.]]

The inner wall itself is divided into two components - the inner neuroblastic layer and the outer neuroblastic layer (see Figure 6). The outer neuroblastic layer forms the rod and cone cells while the inner neuroblastic layer forms the remaining cell types found in the retina - the bipolar, ganglion, horizontal, amacrine and glial cells (Figure 7).<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/> The organisation of the retina is interesting in that incoming light passes through several layers of these neural retina cells before it is detected by rod and cone cells at the back of the retina, and then nerve signals are passed back through the layers of neural retina cells that the light just passed through moments before - a seemingly strange design that the eye does not share with man-made light-capturing devices such as a camera (imagine putting the wires in front of the image sensor!).

Differentiation of the neuroblastic layers into neural retina cells occurs in a pattern both within the layers and across the retina. Cells differentiate from the inner neuroblastic layer to the outer neuroblastic layer, and differentiate from the central retina to the peripheral retina.<ref name="PMID18168748"/> The macula is first identifiable in week 22 when ganglion cells start to form multiple rows, and the primitive fovea begins to form at approximately the same time as a depression in the macula.<ref><pubmed>6462623</pubmed></ref> It is not until 15-45 months after birth that this area becomes exclusively populated by cone cells and becomes the fovea centralis - the area of the retina with the highest visual acuity.

[[File:Formation of the retina 1.jpg|400px|thumb|left|Fig. 6: Cross-section of the primitive retina showing cell types and layers.]] [[File:Formation of the retina 2.jpg|400px|thumb|center|Fig. 7:Cross-section of a developed retina showing cell types and layers.]]

===Ciliary Body===

The ciliary body consists of ciliary processes and three portions of fibres that constitute the ciliary muscles. It functions to maintain normal eye physiology as well as playing a direct role in accommodation.

During development, the ciliary processes form slightly posterior to the iris, developing from part of the anterior rim of the optic cup. It is thought that the folded structure of the ciliary processes is brought about by intraocular pressure and specific signalling pathways.<ref name="PMID16959249"><pubmed>16959249</pubmed></ref> While the ciliary muscles and the endothelial cells of the ciliary blood vessels are chiefly formed by mesenchymal cells<ref><pubmed>16249499</pubmed></ref>, the neural crest and neuroectoderm also contribute to their development.<ref><pubmed>12127103</pubmed></ref> The normal development of the ciliary body is dependent on the correct expression of bone morphogenetic protein (BMP)-4, which is a member of the transforming growth factor-β superfamily.<ref><pubmed>1222340</pubmed></ref> Napier and Kidson (2007) summarised numerous genes that have been associated with ciliary body development, however their direct roles have not been well documented.<ref name="PMID16959249"/>

===Iris===

The iris is a thin layer that develops at the end of the third month of development and is derived from the anterior rim of the optic cup. The stroma of the iris develops from cells of neural crest cell origin.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/> The muscles that are responsible for the dilation and constriction of the pupil (dilator pupillae and sphincter pupillae muscles) form from the neuroectoderm of the optic cup. These cells are initially epithelial cells that then transform into smooth muscle cells. <ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"></ref>. The invagination of the optic vesicle which creates the optic cup, also causes the formation of the optic cup lip. This is the region of the where the epithelium doubles back, separating the outer pigmented layer and the inner nonpigmented layer. This is the edge of the iris that borders on the pupil<ref><pubmed> Retinal and anterior eye compartments derive from a common progenitor pool in the avian optic cup</pubmed></ref>.

The final colour of the iris is not evident until the postnatal period. It is determined by a number of genes including IRF4, SLC24A4 and MATP<ref><pubmed>19710684</pubmed></ref>. Other features such as crypt frequency, furrow contractions, presence of peripupillary pigmented ring, and number of nevi also become evident during development<ref><pubmed>21835309</pubmed></ref>. Mutations in Pax6 have been shown to cause partial or complete loss of the iris <ref><pubmed>12386935</pubmed></ref>.

===Cornea===

The cornea is the transparent, avascular, most anterior portion of the eye. It is responsible for conducting light into the eye and focusing it on to the retina, as well as maintaining the rigidity of the eyeball. It consists of 5 layers- the epithelium, Bowman’s layer, stroma, Descemet’s membrane and the endothelium.

The epithelium and endothelium of the cornea first appear during the 5th week of gestation. The epithelium of the external surface of the cornea is derived from surface ectoderm, while the mesenchyme is derived from the mesoderm<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"/>. The endothelium is a two-cell cuboidal layer which is made up of differentiated neural crest cells that were initially from the optic cup. By week 8 the endothelial cells begin to secrete a basement membrance which later forms Descemet’s membrane<ref><pubmed>6511224</pubmed></ref>. At approximately 16 weeks gestation the Bowman’s membrane begins to form from the thickening of the stroma that is located under the corneal epithelium<ref>Riordan-Eva P, Whitcher JP. Vaughn and Asbury's General Ophthalmology, Lange Medical Books/McGraw Hill. 2004:25–27</ref>. During the third month glycosaminoglycans secreted by fibroblasts form the ground substance of the cornea, with collagen fibrils and keratan sulphate also appearing around this time. Shortly after this tight junctions form between the endothelial cells<ref><pubmed>19481138</pubmed></ref>. Fibroblast growth factor causes the epithelial cells to proliferate<ref><pubmed>20105280</pubmed></ref>.

Towards the end of the gestational period the cornea becomes larger due to the production of aqueous humor<ref>Yanoff M, Duker JS. Ophthalmology. Mosby; St. Louis, MO: 2004</ref>. The final transparent structure develops because hyaluronidase removes hyaluronic acid, thyroxine causes dehydration of the stroma, and the entire structure becomes avascular<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/>. Numerous genes have been implicated in the development of the cornea, these include, but are not limited to, PAX6, PITX2, FOXC1, MAF, TMEM114, SOX2, OTX2 and BMP4<ref><pubmed>18637741</pubmed></ref>. Pax6 and Pax6(5a) isoforms are essential for the normal development of the eye. Over or under expression can both lead to major structural abnormalities<ref><pubmed>18386822</pubmed></ref>.

===Lens===

The lens has its origin from the optic placode, which develops on the ectodermic surface of the embryo and migrates both medially and inwards into the embryo. The lens allows accommodation of the eye, and adjusts its thickness in order to focus on near or far objects. The study of lens development was one of the first to highlight the importance of inductive signaling in development, with Spemann's pioneering work at the start of the 20th century, finding that the absence of retinal development resulted in the absence of lens formation.<ref name="PMID11687490"/> Indeed, it has been consistently shown that the interaction of the migrating optic vesicle with the surface ectoderm of the head is vital in producing differentiation of the lens.<ref name="PMID15558475"><pubmed>15558475</pubmed></ref> The mechanism of interaction is complex but basically involves upstream genes switching on downstream genes, with the genes eventually producing specialised proteins which constitute the lens. The whole process starts with the signaling molecules from the optic cup initiating a thickening of the surface ectoderm of the head (Figure 8). It is thought that this region of specific ectoderm is responsive to the signaling molecules, as lens formation is incomplete or absent when ectoderm from the lateral portion of the embryo (i.e. non-head ectoderm) is exposed to the same inductive signaling processes.<ref name="PMID9216064"><pubmed>9216064</pubmed></ref> Pax6 has been shown to be one of the major genes required for differentiation of the lens, which in turn switches on transcriptional genes such as Sox 1, 2 and 3 among others - producing water-soluble proteins called crystallins - responsible for giving the lens its transparency and refractive properties.<ref name="PMID9609835"><pubmed>9609835</pubmed></ref>

[[File:Formation of the lens 1.jpg|400px|thumb|left|Fig. 8: The importance of the optic cup in lens differentiation.]] [[File:Formation of the lens 2.jpg|400px|thumb|center|Fig. 9: The lens placode separates from the ectoderm and migrates into the mesoderm forming the lens vesicle.]]

The lens placode invaginates from the head ectoderm and migrates into the mesoderm (Figure 9). Once this structure (now known as the lens vesicle) is in place opposite the optic cup, the combined structure is referred to as the optic globe and resembles a recognisable eye structure. The lens continues to differentiate further, as mentioned above, through the formation of crystallin proteins, which give the lens its unique properties and allows for the fine control over the degree of refraction that takes place.

===Aqueous Chambers===

There are both anterior and posterior aqueous chambers of the eye which contain aqueous humour. A space develops in the mesenchyme situated between the lens and cornea to form the anterior aqueous chamber. The mesenchyme located superficially to this chamber forms the mesothelium as well as the transparent portion of the cornea.

The posterior chamber develops from a similar space in the mesenchyme, however it is located between the iris and the lens. The anterior and posterior chambers are able to communicate with one another once the papillary membrane vanishes and the pupil is formed. This channel is known as the scleral venous sinus.<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011">Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011</ref>

Contained within the aqueous chambers is aqueous humor. The production of aqueous humor is dependant on the development of the ciliary body. It is produced in the ciliary processes and it’s production is a metabolic process driven by the delivery of oxygen and the removal of wastes via the ciliary circulation<ref><pubmed>20801226</pubmed></ref>.

===Choroid and Sclera===

The choroid and sclera are adjacent layers that surround the eye and act to vascularise and protect the eye respectively. They are formed from neural crest and mesoderm-derived mesenchyme which condenses around the optic cup and lens vesicle between weeks 5 and 7 of development to form a primitive eyeball structure known as the optic globe.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/> Blood vessels first start to appear in the choroid layer at approximately week 15, and arteries and veins can be distinguished by week 23.<ref>Development of the Choroid and Related Structures, K. Sellheyer, Eye (1990) 4, 255-261</ref> Inductive processes are thought to play a vital role during formation of the choroid and sclera; with the retinal pigmented epithelium inducing differentiation of the surrounding mesenchyme while at the same time the neural crest-derived mesenchyme contributing components to the retinal pigmented epithelium such as melanocytes.<ref name="PMID1628748"/> In addition to having functional roles themselves, the primitive choroid and sclera also contribute components to the developing ciliary body and cornea (Figure 10). In the adult eye, the choroid is continuous with the ciliary body and the sclera with the cornea.

[[File:Formation of the choroid and sclera 1.jpg|400px|thumb|center|Fig. 10: The choroid and sclera derives from mesenchyme surrounding the optic cup.]]

===Eyelids===

The eyelids are ectodermal and mesodermal in origin and are an extension of the skin which covers and protects the eye. The surface ectoderm gives rise to the conjunctiva, skin epithelium, hair follicles, cilia, Zeis glands, glands of Moll, and meibomian glands. <ref name=" Cook CS, Ozanics V, Jakobiec FA. (1994) Prenatal development of the eye and its adnexa. In Tasman W, Jaeger EA, editors: Duane’s foundations of clinical ophthalmology, vol 1, Philadelphia, 1994, Lippincott. "> Cook CS, Ozanics V, Jakobiec FA. (1994) Prenatal development of the eye and its adnexa. In Tasman W, Jaeger EA, editors: Duane’s foundations of clinical ophthalmology, vol 1, Philadelphia, 1994, Lippincott. </ref> The mesenchyme gives rise to the tarsal plates, levator muscles, orbicularis muscles, and tarsal muscle of Muller. <ref name=" Cook CS, Ozanics V, Jakobiec FA. (1994) Prenatal development of the eye and its adnexa. In Tasman W, Jaeger EA, editors: Duane’s foundations of clinical ophthalmology, vol 1, Philadelphia, 1994, Lippincott. "/> Eyelid formation can be first noted during week 5 when small grooves develop in the surface ectoderm (Figure 11).<ref><pubmed>7364662</pubmed></ref> These small grooves deepen and extend into the mesoderm and the primitive eyelid structures grow towards one another, eventually fusing together during week 8.<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"/> It is not until week 26-28 that the eyelids will separate again. The anterior surface of the eyelid becomes covered by two layers of epithelium; this forms the epidermis of the eyelids. <ref name="Kikkawa DO, Lucarelli MJ, Shovlin JP, et al: Ophthalmic facial anatomy and physiology. In Kaufman PL, Alm A, editors: Adler’s physiology of the eye, St Louis, 2003, Mosby, pp 16."> Kikkawa DO, Lucarelli MJ, Shovlin JP, et al: Ophthalmic facial anatomy and physiology. In Kaufman PL, Alm A, editors: Adler’s physiology of the eye, St Louis, 2003, Mosby, pp 16.</ref> Tarsal plates then begin to develop, which eventually leads to the formation of meibomian glands. <ref name="PMID1628748"/> The ectoderm reflects over the developing cornea to form the conjunctival sac, a space that is filled by secretions from the lacrimal gland in order to allow smooth motions of the eyelid over the eye and also to clean the cornea and prevent accumulation of particles on the eye that may disrupt vision. By the time the eyelids separate, the eye has all its major components present (Figure 12), and further development consists mainly of growth and vascularisation.

[[File:Formation of the eyelid 1.jpg|400px|thumb|left|Fig.11: Small grooves in the ectoderm of the head - the precursors to an eyelid.]] [[File:Formation of the eyelid 2.jpg|400px|thumb|center|Fig. 12: The eye after week 8 of development. Note however, that the eyelids remain fused until weeks 26-28.]]

===Lacrimal Glands===

There are three stages of lacrimal gland development. The first is the presumptive glandular stage in which the superior conjunctival fornix epithelium thickens and the surrounding mesenchymal cells condense. These mesenchymal cells are of neural crest origin<ref><pubmed>9882499</pubmed></ref>. The second stage sees the development of nodular formations around the superior conjunctival fornix and the formation of lumina within the epithelial buds, this stage is therefore known as the bud stage. Innervation and vascularisation also occur during this stage. The final morphological changes occur during the glandular maturity stage which occurs in weeks 9-16 when the lacrimal glands begin to resemble the mature glands. During the 13th week the lacrimal and zygomatic nerves anastomose<ref><pubmed>14635806</pubmed></ref>.

These glands are responsible for the production of tears however they do not start to function until 1-3 months after birth. The mature lacrimal gland is made up of two lobes- the palpebral and orbital lobes.

==Current Research==

Not only are there still many important processes and components of eye development that we would like to understand, this knowledge also contributes to the development of treatments for eye disorders and technologies such as the bionic eye.

===The impact of visible light on the immature retina===

<pubmed>22405869</pubmed>

The authors mentioned in this article <ref name="PMID22405869"><pubmed>22405869</pubmed></ref> that they were interested in investigating the effect of light on postnatal eye development in mice, because mice are born with fused eyelids, which separate 12 days after birth. Before the eyelids separate, the retina develops in mice with very little radiation from light. It is believed that the darkness plays a role in the development of the retina in mice, which is why their eyelids are fused for 12 days after birth. Therefore the authors were interested to see what effect light would have on postnatal retinal development of mice, with special interest in retinal ganglion cells (RGC). In their experiment, they surgically opened the eyelids on the right eyes of some of the mice to expose them to visible light 12 hours per day, while they left some other mice in the dark after surgical separation of their eyelids. They also kept the left eyes of the mice naturally fused as controls in the experiment. Their results showed that early light exposure in mice causes a decrease in retinal ganglion cells because it affects cellular apoptosis in the retina. The authors also observed that early exposure to light in mice causes lumican mRna transcription to resume and to quickly increase. (Lumican normally stays silent in retina after birth).

---------

===GABA Maintains the Proliferation of Progenitors and Non-Pigmented Ciliary Epithelium===

<pubmed>22590629</pubmed>

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| GABA is an ‘inhibitory neurotransmitter’ in the central nervous system of adults. <ref name="PMID22590629"><pubmed>22590629</pubmed></ref> It is responsible for controlling proliferation of stem cells and progenitor cells. The authors of this article <ref name="PMID22590629"/> was interested to find the effects of GABA on proliferation of progenitor cells and non-pigmented ciliary epithelial cells (NPE) in the retina. Their study focused on progenitor cells and non-pigmented epithelium of the ciliary body in chickens. Non-pigmented epithelial cells in chickens arise from the neuroepithelium of the optic cup. They share similar functions as progenitors of the early retina, such as expression of Chx10 and Pax6 genes. It is not agreed upon whether epithelial cells of the ciliary body have stem cell properties. However, it has been found that these cells can be cultured and transplanted into retinas that are injured, in order to replace neurons that were previously lost. However, there is not much known about what factors regulate the proliferation of stem cells. Hence the authors were interested in finding the effects of GABA on proliferation of retinal cells. Their results showed that non-pigmented epithelial cells in chickens ‘express extrasynaptic-like GABAA receptors’ that have the ability to regulate cell proliferation. It has been found that inhibiting these ‘GABAA receptors’ also causes a decrease in proliferation of retinal progenitor cells and non-pigmented epithelial cells in 'the intact E8 retina’. <ref name="PMID22590629"/>

|
[[File:Gaba-effects-retina.JPG|thumbnail|250px|'''GABAA receptor mediated effects on retinal progenitor cell proliferation'''
]]
|}

-------------------------

===Stem Cells===

[http://www.advancedcell.com/patients/clinical-trial-information/ Advanced Cell Technology] is a biotechnology company which is currently running two clinical trials that utilise human embryonic stem cell derived retinal pigmented epithelial cells. These trials are examining the possibility of using these cells to treat stargardt's macular dystrophy and dry age-related macular degeneration.

Despite the discovery of human embryonic stem cells (hESCs) 13 years ago, these trials are the first to describe the subretinal transplantation of hESCs into humans. The participants in these trials were sufferers of Stargardt's macular dystrophy or dry age-related macular degeneration, which is the chief cause of blindness in the developed world.

The trials were relatively successful in the sense that the hESC-derived retinal pigment epithelium cells that were implanted integrated well into the existing tissue, and there were no signs of hyperproliferation, abnormal growth, or rejection. The authors hope that in future this technique will be applied to patients in the earlier stages of disease, preventing disease progression<ref><pubmed>22281388</pubmed></ref>.

-------------------

===MIP/Aquaporin 0 Represents a Direct Transcriptional Target of PITX3 in the Developing Lens===

<pubmed>21698120</pubmed>

{| width=800px
|-
|PITX3 plays a siginificant role in the development of lens in vertebrates. If there is a deficiency is PITX3, it causes a range of problems in humans such as microphthalmia, Peter’s anomaly, or isolated cataracts. Mutation of PITX3 also causes degeneration of the lens in zebrafish and mice. It is therefore important to understand what factors may affect the decrease in PITX3, as a normal level of PITX3 is needed to maintain normal eye development. The authors wanted to investigate specific genes which are affected by PITX3. Previous research has shown that MIP and Aquaporin causes defects in the lens in both mice and humans. MIP and Aquaporin are targeted by PITX3, so their imbalance is interrelated in the cause of defects in the lens. Therefore it has been previously proven that PITX3 is needed for normal development of the lens. However, there has not been much information previously known regarding the exact effect that PITX3 has, or the specific genes it targets. Since MIP and Aquaporin is common genes found in humans, mice and zebrafish, the authors <ref name="PMID21698120"><pubmed>21698120</pubmed></ref> chose to study these genes to understand the pathway that PITX3 takes and its exact involvement in the development of the lens. Their results proved that deficiency in MIP and Aquaporin indeed affects normal development of the lens, and it is indeed related to deficiency in PITX3. However, there is still more research needed to understand PITX3 and the genes it interacts with, and their effect in ocular development.

|
[[File:Mip1-expression-in-pitx3.jpg|thumbnail|250px|'''Analysis of mip1 expression in pitx3-mo and control embryos via in situ hybridization and RT-PCR''']]
|}

-------------------

===Activation of c-Jun N-terminal kinase (JNK) during mitosis in retinal progenitor cells.===

<pubmed>22496813</pubmed>

{| width=800px
|-
| In the past, most studies about c-Jun N-terminal kinase (JNK) in the retina have been in relation to neurodegeneration. <ref name="PMID22496813"><pubmed>22496813</pubmed></ref> Therefore the authors in this article were interested in investigating the function of c-Jun N-terminal kinase in the retinal progenitor cells in neonatal rats. <ref name="PMID22496813"/> In the experiment, they took retinal tissue from newborn rats and fixed them, and subsequently examined them using confocal microscopy and fluorescence to discover c-Jun N-terminal kinase ‘phosphorylation by immunohistochemistry’. <ref name="PMID22496813"/> Mitotic cells in the retina were identified during the experiment. The results of their experiment revealed that c-Jun N-terminal kinase is phosphorylated in the developing retina of neonatal rats during the mitosis of progenitor cells. <ref name="PMID22496813"/> This shows that c-Jun N-terminal kinase can control the proliferation of progenitor cells in the developing retina. Their experiment also revealed that inhibiting c-Jun N-terminal kinase causes disruptions to the mitotic cell cycle by reducing the cell numbers in anaphase. <ref name="PMID22496813"/> However, inhibiting c-Jun N-terminal kinase did not change the cell numbers in metaphase or prophase. <ref name="PMID22496813"/>

|
[[File:JNK1.png|thumbnail|300px|'''"JNK is phosphorylated during mitosis of retinal progenitor cells."''']]
|}

----------------------------

===LRP5 is required for vascular development in deeper layers of the retina===

<pubmed>20652025</pubmed>

{| width=800px
|-
|
The lipoprotein receptor-related protein 5 (LRP5) has a significant function in the development of retinal vasculature.<ref name="PMID20652025"><pubmed>20652025</pubmed></ref> Research has shown that mutations of the LRP5 causes loss of function, due to incomplete development of retinal vessel network, in both humans and mice. The authors investigated how mutations occur in the LRP5, which leads to abnormal development of the retinal vasculature. They have studied retinal endothelial cells in mutant mice in their study. Their results showed that in retina with mutated LRP5, endothelial cells in the retinal vasculature primarily produced cell clusters in the inner-plexiform layer instead of migrating into deeper layers of the retina to form normal retinal vasculature. The authors also discovered that there was a decrease in Slc38a5, which is “a Müller cell-specific glutamine transporter”, in mice with mutated LRP5. Their results lead the authors to conclude that normal LRP5 is very important in the development of normal retinal vasculature due to their role in causing migration of retinal endothelial cells in the deeper layers of the retina. LRP5 is also important for retinal interneurons and Müller cells to function correctly.

|
[[File:Retina-cell-clusters.JPG|350px|thumbnail|'''Endothelial cells form thick clusters in the LRP5 mutant retina''']]
|}

-----------------

===Astrocyte-Derived Vascular Endothelial Growth Factor===

<pubmed>20686684</pubmed>

{| width=800px
|-
|
Vascular endothelial growth factor (VEGF) has an important role in normal development of retinal vasculature. <ref name="PMID20686684"><pubmed>20686684</pubmed></ref> In the process of vascularisation of the retina, the retinal astrocytes (both vascularised and not yet vascularised) expresses the vascular endothelial growth factor. <ref name="PMID20686684"/> This fact indicates that vascular endothelial growth factor that are derived from astrocytes of the retina plays an important role in vessel maturation and angiogenesis. <ref name="PMID20686684"/> Therefore the authors wanted to test the role of vascular endothelial growth factor that are derived from astrocytes to find further confirmation. ‘Cre-lox technology’ was used in the experiment to remove the vascular endothelial growth factor from mice retinal astrocytes in the developmental period. <ref name="PMID20686684"/> The results showed that removing vascular endothelial growth factor that are derived from astrocytes caused ‘the regression of smooth muscle cell-coated radial arteries and veins’ from the effects of hyperoxia. <ref name="PMID20686684"/> Hence, this result indicates that vascular endothelial growth factor plays an important role in stabilising blood vessels during the development of the retinal vasculature. <ref name="PMID20686684"/> It has been suggested that this finding may be of relevance to retinopathy in premature neonatal humans. <ref name="PMID20686684"/>

[[File:Astrocyte-vegf-deletion.JPG|250px|thumbnail|'''"Astrocyte specific deletion of VEGF." ''']]
|
[[File:Effect-of-vegf-on-retinal-vasculature.JPG|250px|thumbnail|'''"Effects of astrocyte-derived VEGF on retinal vascular development."''']]
[[File:Vegf-protects-vessels.JPG|250px|thumbnail|'''Astrocyte-derived VEGF protects vessels from hyperoxia. ''']]

|}

==Useful Links==

{{External Links}}

[http://www.youtube.com/watch?v=Xme8PA6xv-M Visualisation of eye development in the embryo]

[http://www.youtube.com/watch?v=wJE6pYwAMVU Brief Video on Embryonic development of the eyes]

[http://www.embryo.chronolab.com/sense.htm Embryonic Development of the eye]

[http://webvision.med.utah.edu/book/ Webvision free online textbook]

[http://www.ophthobook.com/chapters/ Free basic online book about the eyes]

[http://www.youtube.com/watch?v=deEjbVdnwyA&feature=related Anatomy of the Eyes- Video]

==Glossary==

'''Accommodation''' - changing the focal length of the lens in order to focus on an object.

'''Downstream genes''' - genes that are activated by other "upstream genes".

'''Ectoderm''' - outermost layer of germ cells in an early embryo.

'''Endoderm''' - innermost layer of germ cells in an early embryo.

'''Glial cells''' - non-neuronal cells that provide structure and protection to neurons as well as producing myelin.

'''Inductive signaling''' - a process whereby the secretion of factors from one cell or tissue triggers a response in another.

'''Lens vesicle''' - the cavity of invaginated ectoderm from the optic placode that will form the lens.

'''Macula''' - a highly pigmented, oval-shaped area located near the centre of the retina. Important for visual acuity.

'''Mesenchyme''' - undifferentiated, loose connective tissue.

'''Mesoderm''' - middle layer of germ cells in an early embryo.

'''Mesothelium''' - the epithelial layer of the mesoderm.

'''Myelinisation''' - development of a myelin sheath around a nerve fibre.

'''Neural crest''' - a portion of the ectoderm situated next to the neural tube.

'''Neural groove''' - a large invagination on the dorsal surface of the embryo which will close off and form the neural tube.

'''Neural tube''' - hollow structure that results from the folding of the neural plate and eventually forms the central nervous system.

'''Neuroblastic layer''' - a layer of immature cells that differentiate to form either glial cells or neurons. The retina has two of these (an inner and outer).

'''Neuroectoderm''' - portion of the ectoderm that develops to form the central and peripheral nervous systems.

'''Optic chiasm''' - the point at which the optic nerves meet and cross over.

'''Optic cup''' - the structure that is formed after the optic vesicle folds in upon itself. This will form the retina.

'''Optic globe''' - a term that refers to the optic cup, lens vesicle and surrounding mesenchyme collectively.

'''Optic placode''' - area of thickened ectoderm that gives rise to the lens of the eye.

'''Optic stalk''' - a long, narrow cavity that will produce the optic nerve.

'''Optic vesicle''' - a cavity that buds off from the neural tube and gives rise to the optic cup.

'''Upstream genes''' - genes that activate one or more other "downstream genes".

'''Vascularise''' - to invade with blood vessels.

==Image Gallery==
<gallery>
Image:Eye_diagram_bandw.jpg‎ | Basic structure of the human eye.
Image:Stage14 sem2b-limb.jpg | A Stage 14 embryo showing the location of an otic placode.
Image:Stage 13 image 060.jpg | A cross section showing the organisation of the developing brain, the optic vesicle and the lens (optic) placode.
Image:Formation of the optic vesicle 1.jpg | Early formation of the optic vesicle from the neural groove.
Image:Formation of the optic vesicle 2.jpg | The optic vesicle at a later stage, showing the optic stalk.
Image:Formation of the optic nerve and chiasm 1.jpg | A recognisable brain and eye structure in later development.
Image:Formation of the optic cup 1.jpg | Mechanism of optic cup formation.
Image:Formation of the optic cup 2.jpg | Layers of the optic cup in retina development.
Image:Formation of the retina 1.jpg | Cross-section of the primitive retina showing cell types and layers.
Image:Formation of the retina 2.jpg | Cross-section of a developed retina showing cell types and layers.
Image:Formation of the lens 1.jpg | The importance of the optic cup in lens differentiation.
Image:Formation of the lens 2.jpg | The lens placode separates from the ectoderm and migrates into the mesoderm forming the lens vesicle.
Image:Formation of the choroid and sclera 1.jpg | The choroid and sclera derives from mesenchyme surrounding the optic cup.
Image:Formation of the eyelid 1.jpg | Small grooves in the ectoderm of the head - the precursors to an eyelid.
Image:Formation of the eyelid 2.jpg | The eye at an advanced stage of embryonic development. Note however, that the eyelids remain fused until much later.

</gallery>

==References==
<references/>

----

--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

----

{{2012Projects}}

2012 Group Project 1

2012-10-03T00:15:36Z

Z3254758: /* Current Research */

[[File:Eye_collage_2.jpg|right|830px]]

=Vision Development=

==Introduction==

Eyes are an important sensory organ shared across many different species and allow organisms to gather useful visual information from their environment. The visual system uses light from the environment and processes this information in the brain for visual perception. The visual system is complex, and is made up of various structures that work together to form vision. Each of the structures in the eye have specific tasks which contribute to the visual system. Knowledge of how the eye develops extends as far back as Aristotle more than 2000 years ago, and current knowledge shows that most of the crucial events of eye development occur in the embryological stage. The eye is an interesting model for studying the development of tissues in organisms, as it consists of cells from several parts of the embryo including the head ectoderm, neural ectoderm and mesoderm. From its many origins the cells come together and differentiate to produce the complex organ that is the eye. During this period there are many examples of inductive signaling, as the tissues coordinate their development throughout this elegant process.

The main anatomical structures of the eye are as follows:
{|
|
* Cornea

* Sclera

* Choroid

* Iris

* Ciliary body

* Lens

* Anterior chamber

* Posterior chamber

* Retina

* Optic nerve

|[[File:eye_diagram_bandw.jpg|right|250px|thumb|Basic structure of the human eye.]]
|}
[[File:Eyediagramcolour1.JPG|550px]]

==Research History==

=== '''Brief Timeline of Historical Developments on the Eye and its Embryology''' ===

{| width=800px
|-bgcolor="CEDFF2"
| width=100px|'''Time'''
| width=700px|'''Discovery'''

|-bgcolor="F5FAFF"
| '''Ancient Egyptians'''
| First to document cataracts. It is described as being 'the white disease of the eye' or 'darkening of the pupil.' <ref>Edwards, D.D. (1996). Ophthalmology before Hippocrates. In the History of Ophthalmology, ed. D.M. Albert and D.D. Edwards. Cambridge, Mass.: Blackwell Science.</ref> The Egyptians had some knowledge of the eye, however it is not known how much of the anatomy of the eye was known in their era.

|-bgcolor="CEDFF2"
| '''535 BC'''

|
Ancient Greek philosopher Alcmaeon conducted dissection of humans for the first time in recorded history. This included dissection of the eye. However, not much is known about which anatomical features he discovered. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17.">Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17.</ref>

|-bgcolor="F5FAFF"
| '''384- 322 BC'''

| [[File:Aristotle-eye.jpg|200px|thumbnail|The eye according to Aristotle.<ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "> Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau </ref> Note the lens is missing, and there are three vessels drawn that was believed to transport fluid to and from the eye.<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
]]
Aristotle performed dissections of animal embryos.<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

When Aristotle described the embryo of a ten day old chicken, he wrote "The eyes about this time, if taken out, are larger than beans and black; if their skin is removed the fluid inside is white and cold, shining brightly in the light, but nothing solid." <ref name="Magnus, H. (1998). Ophthalmology of the ancients. In J. Hirschberg (Ed.), The History of Ophthalmology: The monographs, Vol. 4, Part 1 (F.C. Blodi, Trans.) Bonn: Wayenborgh.">Magnus, H. (1998). Ophthalmology of the ancients. In J. Hirschberg (Ed.), The History of Ophthalmology: The monographs, Vol. 4, Part 1 (F.C. Blodi, Trans.) Bonn: Wayenborgh.</ref>

Aristotle believed that the eyes started forming during early embryogenesis, however, he also believed that the eyes are the last organs to form completely, and he incorrectly thought that the eyes shrink in later embryonic development. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press.">Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press.</ref> .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"

| '''340 BC'''

| Lens is thought to have been discovered by Hippocrates, due to his descriptions of the contents of the internal eye There has been studies in chick development later on by followers of Hippocrates. They claimed that eyes were visible in early embryogenesis. .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
|-bgcolor="F5FAFF"
|'''25 BC - 50 AD'''

| [[File:Celsus-eye.jpg|150px|thumb|The eye according to Celsus. <ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "/>
Note the lens is placed in the centre of the eye, in the vitreous.<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> ]]

Aulus Cornelius Celsus wrote a Roman medical text called 'De Medicina' in which he wrote that the lens was the part of the eye from which vision originated. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.">Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.</ref> Celsus also incorrectly drew the lens in the center of the globe in his diagram of the eye. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

|-bgcolor="CEDFF2"
| '''23-79 AD '''
|
Pliny the Elder said that the eye is the last of the organs to develop in the womb <ref name="Magnus, H. (1998). Ophthalmology of the ancients. In J. Hirschberg (Ed.), The History of Ophthalmology: The monographs, Vol. 4, Part 1 (F.C. Blodi, Trans.) Bonn: Wayenborgh."/>
|-bgcolor="F5FAFF"
| '''98-117 AD'''

| [[File:Rufus-eye.jpg|150px|thumb|The eye according to Rufus of Ephesus. <ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "/>
Note the lens is placed in the correct position, behind the iris of the eye <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> ]]

Rufus of Ephesus identified the lens as being located in the anterior part of the eye, close to the pupil. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

His diagram illustrates that he knew the correct position of the lens as being directly behind the iris, in the anterior part of the eye, and not in the centre as was previously depicted by others before him.

|-bgcolor="CEDFF2"
| '''130-200 AD'''

| [[File:Galen-eye1.jpg|150px|thumb|The eye according to Galen. <ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "/> ]]

Claudius Galen practised medicine in Rome. He wrote:

"1. Within the eye the principal orgran of sensation is the crystalline lens.

2. The sensation potential comes from the brain and is conducted via the optic nerves.

3. All other parts of the eyeball are supporting structures." <ref> Hirschberge, J. (1982). Antiquity, Vol. X in the History of Ophthalmology (F.C. Blodi, Trans.) Bonn: Wayenborgh. pp. 280 </ref>

Galen thought that the lens was produced from the vitreous. He also believed that the retina’s function was to give nourishment to the lens and vitreous, and to carry visual information to the brain from the lens. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

|-bgcolor="F5FAFF"

| '''1514-1564'''

| Andreas Vesalius published his anatomy book "De Humani Corporis Fabrica in 1543. He had the misconception that the lens was located in the centre of the eyeball. .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> He also wrote that the lens functioned "like a convex lens made of glass" <ref name="Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.">Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.</ref> pp. 48
|-bgcolor="CEDFF2"
| '''1535-1606'''

| Georg Bartisch correctly drew a diagram of the lens placed behind the iris in his book 'Ophthalmodouleia: das ist Augendienst'. <ref name="Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>
|-bgcolor="F5FAFF"

| '''1537-1619'''

| Fallopio Hieronymus Fabricius ab Aquapendente studied anatomy and embryology. He studied chicken embryos, and thought that chalazae (which comes from egg white) gives rise to the eyes. He also drew the lens directly behind the iris in a diagram in is book 'Tractatus de Oculo Visuque Organo. <ref name="Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

|-bgcolor="CEDFF2"
| '''1583'''

| Felix Platter published his book 'De corporis Humani Structura et Usu, after he performed dissections of human bodies. He believed that the retina is the primary visual organ in the eye. .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="F5FAFF"
| '''1619'''
| Scheiner is given credit to be the first person to correctly draw the diagram of the anatomy of the eye. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
|-bgcolor="CEDFF2"
| '''1672'''
| Marcello Malpighi described the embryonic development of the chicken. He drew many detailed diagrams of the chick eye. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1665'''
| Nicolaus Steno identified the choroid fissure in his study of a developing embryo of a chicken. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="CEDFF2"
| '''1754'''

| Albrecht von Haller studied the embryology of the eye. With help from his student Johann Gottfried Zinn, he contributed to the understanding of the development of the ciliary body, ciliary zonule, and their relationship with the lens and vitreous. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1817'''

| Christian Pander discovered the three embryonic germ layers, which he wrote about in his book. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/> Pander was the first to think of 'the optic vesicles as lateral evaginations' of the 'prosencephalon'; however, he was incorrect about the details regarding how 'the eye develops from these evaginations'. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="CEDFF2"
| '''1828-1837'''

| Karl Ernst von Baer studied embryology. He discovered that the optic vesicles were 'outgrowths of the embryonic forebrain' <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> which he believed was caused by pressure from fluids in the central nervous system. Von Baer also believed that the optic vesicle opens to form the pupil, and that fluid in the optic vesicle coagulates to form the vitreous body and lens. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1830'''

| Emil Huschke discovered that the lens forms from the invagination of the surface ectoderm. He concluded that the lens hence does not form ‘from the fluid of the optic vesicle’ <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> as previously thought.
|-bgcolor="CEDFF2"
| '''1832'''

| Emil Huschke wrote in his manuscript ‘Ueber die erste Entwinkenlung des Auges und die damit zusammenhängende Cyklopie’ that the lens capsule forms from the outer surface ectoderm, which detaches and moves back inward, which is later enclosed again by several membranes, such as by the cornea. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

Huschke also described how the optic cup and choroid fissure forms. He discovered that the optic vesicles are produced from the two-layered optic cup. However, he incorrectly described the destiny of the ‘individual optic cup layers’. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

|-bgcolor="F5FAFF"
| '''1838'''
| Matthias Jakob Schleiden and Theodor Schwann formulated the ‘cell theory’: “All living things are formed from cells, the cell is the smallest unit of life, and cells arise from pre-existing cells.” <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
|-bgcolor="CEDFF2"
| '''1839'''

| Theodor Schwann contributed a better understanding of the development of the lens through studying the foetus of a pig, which he wrote about in his book ‘Mikroskopische Untersuchungen Über Die Uebereinstimmung in Der Struktur Und Dem Wachsthum Der Thiere Und Pflanzen’. He wrote that the lens is made of ‘concentric layers’ of fibres which proceeds from an anterior to posterior direction. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1842'''
| Robert Remak gave the current names to the three embryonic germ layers: ectoderm, mesoderm and endoderm. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"
| '''1843'''
| Wilhelm Werneck published his book ‘Beiträge zur Gewebelehre des Kristallkörpers’. He wrote that the contents inside of the lens is not made of fluids, as was previously believed. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/> Werneck also discovered that the fibers of the lens continues to grow from the outside to the centre during embryogenesis. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

|-bgcolor="F5FAFF"
| '''1855'''

| Robert Remak wrote his book ‘Untersuchungen über die Entwickelung der Wirbelthiere’. He wrote about what he discovered in his studies of the development of the eye in the embryos of chickens, frogs, and rabbits. He wrote very descriptively about the embryology of lens formation, amongst other topics. He discovered that the ectoderm gives rise to the lens placode. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

|-bgcolor="CEDFF2"
| '''1858'''
| Henry Gray published his book 'Anatomy, Descriptive and Surgical'. He had also previously studied the embryonic development of the optic nerve and retina of chickens.
|-bgcolor="F5FAFF"
| '''1877'''
| Paul Leonhard Kessler wrote about the embryonic development of the lens in mice in his book ‘Zur Entwickelung des Auges der Wirbelthiere. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"
| '''1891'''
| Vincenzo Colucci studied newts and discovered their ability to regenerate the lens.<ref> Tsonis, P. A. (2001). Regeneration of the Vertebrate Lens and Other Eye Structures. eLS. (Online Publication). DOI: 10.1038/npg.els.0001102 </ref>
|-bgcolor="F5FAFF"
| '''1892'''
| Dr. Oscar Hertwig published his book ‘Text-Book of the Embryology of Man and Mammals. <ref> Hertwig, O. Text-book of the embryology of man and mammals. S. Sonnenschein 1901. (Translated from the 3d German ed. by Edward L. Mark.) </ref> It contains a very detailed description of the development of the eye, according to the findings at that time. [http://embryology.med.unsw.edu.au/embryology/index.php?title=Book_-_Text-Book_of_the_Embryology_of_Man_and_Mammals_16-2#The_Development_of_the_Eye]
|-bgcolor="CEDFF2"
| '''1895'''
| Gustav Wolff also independently studied newts and discovered their ability to regenerate the lens. .<ref> Tsonis, P. A. (2001). Regeneration of the Vertebrate Lens and Other Eye Structures. eLS. (Online Publication). DOI: 10.1038/npg.els.0001102 </ref>

|-bgcolor="F5FAFF"

| '''1900'''
| Carl Rabl published his book ‘Uber den Bau und die Entwicklung der Linse’. He wrote about the development of the lens in mammals, fish, birds, reptiles, and amphibians. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"
| '''1901'''
| Hans Spemann published his findings from his experimental studies about the formation of the lens in the frog. He found that the optic cup needed to be in contact with the ectoderm for normal development of the eye. <ref> Spemann, H. (1901). Über Correlationen in der Entwicklung des Auges. Verhand. Anat. Ges. 15: 61-79. </ref> <ref> Saha, M. (1991). Spemann seen through a lens. In Gilbert, S. F. (ed.). A Conceptual History of Modern Embryology. Plenum Press, NY. pp. 91-108.</ref>
|-bgcolor="F5FAFF"
| '''1906'''
| Brown ‘s book “The Embryology Anatomy and Histology of the Eye” was published. It contained detailed descriptions of the embryonic development of the eye according to the knowledge current at that time, mainly based on observations from embryos of rabbits and chickens. <ref> Brown, E.J. (1906). The Embryology Anatomy and Histology of the Eye. Chicago: Hazlitt & Walker. 1906 </ref>

|-bgcolor="CEDFF2"
| '''1907'''

| John Clement Heisler published his book ‘A Text-book of embryology’. It contains a chapter detailing the embryonic development of the eye, according to the knowledge current at that time. The book’s copyright has expired, so it can be viewed free online: [http://archive.org/details/atextbookembryo01heisgoog]

Julius Kollman also published his book 'Atlas of the Development of Man'. It contained very detailed description and illustrations showing the embryonic development of the human according to the knowledge current at that time. His illustrations were reused by many others after his time and built upon for further refined understanding of the embryology of the human.

Here are examples of Julius Kollman's excellent illustrations showing eye development in various stages:

'''Formation of Primary Optic Vesicle:'''
<gallery>
File:Kollmann691.jpg|The blue part at the bottom is the endoderm. The pink middle layer is the mesoderm. The top yellow layer is the ectoderm. The fold labelled as 'augenfeld' is the place where the optic vesicle will form.
File:Kollmann692.jpg|The eye area (augenfeld) is a bowl shaped bulge still located on the side walls.
File:Kollmann693.jpg| The neural tube is shown after removal of all of the ectoderm and ventral organs, such as heart, gut tube, etc. The primary optic vesicle forms a slightly flattened hollow protrusion on the forebrain.
File:Kollmann694.jpg|The lateral surface of the primary optic vesicle is slightly depressed, showing the first sign of the emergence of the secondary optic vesicle
</gallery>

'''Development of Lens:'''

<gallery>
File:Kollmann695.jpg|The bulging lateral wall of the primary optic vesicle is covered by a fairly well demarcated lens plate, a direct continuation of the ectoderm. Between the optic vesicle and the lens pit are some flattened spindle-shaped cells. In the adjoining mesoderm are cross-sections of capillaries.
File:Kollmann697.jpg|The lens still hangs together with the ectoderm. The primary eye vesicle is indented with respect to the lens. Between the lens and the lateral plate of the optic vesicle is a narrow space, which allows area to further develop later.
File:Kollmann698.jpg|4th Week of development. The internal organisation shows the secondary optic vesicle. A: The rear wall of lens is noticeable and is enveloped by mesoderm. B: The edges of the lens pit is already grown and the lens vesicles are formed, which is still related to the remaining ectoderm.
File:Kollmann699.jpg|The lens has now cut off from the ectoderm, but is still very superficial. Between it and the lateral lamina of the optic cup, there is a considerable space. The eye stalk has become longer and is enclosed together with the optic cup and lens of the mesoderm. The cornea, sclera and choroid make gradual development.
</gallery>

|-bgcolor="F5FAFF"

| '''1921'''
| Bailey and Miller published their textbook “Text-Book of Embryology “. <ref> Bailey, F.R. and Miller, A.M. (1921). Text-Book of Embryology. New York: William Wood and Co. (Note- This book is only at an early edited stage)</ref> It contains detailed description of the development of the embryonic eye according to the knowledge current at that time. [http://embryology.med.unsw.edu.au/embryology/index.php?title=Book_-_Text-Book_of_Embryology_18]

|-bgcolor="CEDFF2"
| '''1925'''

| Mann published his research article, in which he gives a detailed account of the development of the human iris. He divided the development of the iris into four stages: weeks 4-7 (before the ectodermal iris forms or before the anterior chamber forms); weeks 7-11 (anterior chamber appears, and mesodermal iris forms); weeks 11-12 (ectodermal iris forms); 3-8 months (muscles of the pupil forms from ectodermal iris, and the central portion of the mesodermal iris atrophies to make the pupil clear). <ref name="PMID18168466"><pubmed>18168466</pubmed></ref>
O Leser also published an article detailing the development of extraocular muscles in mammals he studied. <ref name="PMID18168498"><pubmed>18168498</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1939'''
| Holtfreter <ref> Holtfreter, J. (1939). Gewebeaffinitat, ein Mittel der embryonalen
Formbildung. Arch. Exp. Zellforsch. 23, 169-209. </ref> studied amphibians and observed that that the development of the eye stops at the ‘optic vesicle stage’ if there is no contact ‘with the epidermis and neural crest driven mesenchyme’. <ref name=”PMID11023863”><pubmed>11023863</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1955'''
| Barber published his book ‘Embryology of the human eye’. <ref> Barber AN: Embryology of the human eye. St. Louis. CV Mosby 1955</ref> In contains detailed descriptions of the embryological development of the human eye according to the knowledge current at that time. It contains many photographs of the eye at different stages of development.

|-bgcolor="F5FAFF"
| '''1957'''
| Coulombre studied a chicken embryo to find the role of intraocular pressure in the development of the chick’s eye, especially in regards to its control of the size of the eye structures. <ref name="PMID13469954"><pubmed>13469954</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1958'''
| Coulombre studied the development of the cornea and how it develops its transparency. <ref name="PMID13563560"><pubmed>13563560</pubmed></ref> He also studied the development of corneal curvature. <ref name="PMID 13519969"><pubmed> 13519969</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1962'''
| Coulombre studied the development of the conjunctival papillae and scleral ossicles. <ref name="PMID 14023393"><pubmed> 14023393</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1963'''
| Coulombre studied the development of lens fibers and their orientation. <ref name="PMID14077035"><pubmed>14077035</pubmed></ref> He also studied the development of pigmented epithelium. <ref name="PMID14023394"><pubmed>14023394</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1964'''

| Coulombre further studied the development of the lens to determine the role of the lens in eye growth. <ref name="PMID14189921"><pubmed>14189921</pubmed></ref> He also studied the role of thyroid in the development of the cornea and the development of corneal transparency. <ref name="PMID14211912"><pubmed>14211912</pubmed></ref> Mann also published his work called ‘The development of the human eye’, which contains detailed description of the embryonic development of the eye according to current knowledge at that time. <ref> Mann I. The development of the human eye. New York: Grune and Stratton 1964</ref>

|-bgcolor="CEDFF2"
| '''1965'''
| Coulombre published his findings regarding the regeneration of the neural retina from pigmented epithelium in the embryo of chickens. <ref name="PMID5833111"><pubmed>5833111</pubmed></ref> Smelser also published his findings on the embryological development and morphology of the lens. <ref name="PMID14340157"><pubmed>14340157</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1966'''

| Formation of the face and orbit occurs from the differentiation of neural crest cells. <ref name="PMID5969670"><pubmed>5969670</pubmed></ref> O’Rahilly also published findings of the development of the eye in the early stages of human embryos. <ref> O'Rahilly, R. 1966 The early development of the eye in staged human embryos. Contr. Embry. Carnegie Inst., Wash., 38: 1–42</ref>

|-bgcolor="CEDFF2"
| '''1968'''
| Findings of the postnatal development of the retina of rats was published. <ref name="PMID5640327"><pubmed>5640327</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1969'''

| Mann again published his work called ‘The development of the human eye’. He stated that that the lens in humans forms completely from the ectoderm. <ref name=”Mann I. The Development of the Human Eye. New York, USA: Grune & Stratton, Inc; 1969”> Mann I. The Development of the Human Eye. New York, USA: Grune & Stratton, Inc; 1969</ref> Coulombre also studied the development of the lens, and took note of its size, shape and orientation throughout its developmental stages. <ref name="PMID 5772716"><pubmed> 5772716</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1970'''
| Coulombre again further studied the regeneration of the neural retina from pigmented epithelium of embryos of chickens. <ref name="PMID 5472476"><pubmed> 5472476</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1971'''

| Coulombre further studied the development of the lens. This time he focused on analysing the histological mechanisms in the reconstitution of the lens from implanted lens epithelium. <ref name="PMID 4925671"><pubmed> 4925671</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1973'''
| A research article was published, detailing the embryonic development of the retina of humans. <ref name="PMID 6650859"><pubmed> 6650859</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1976'''

| Geeraets published his observations of the closure of the embryonic optic fissure in golden hamsters, using the electron microscope. <ref name="PMID 1266776"><pubmed> 1266776</pubmed></ref> Kornneef also published an article based on his studies of the development of connective tissue in the human orbit. <ref name="PMID 1020699"><pubmed> 1020699</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1981'''
| A research article was published detailing how myelin forms in the optic nerve of humans. <ref name="PMID 7224936"><pubmed> 7224936</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1983'''
| O’Rahilly’s further research developments was published, reporting the timing and sequence of events in the development of the embryonic human eye. <ref name="PMID 6650859"><pubmed> 6650859</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1990'''

| Van Driell et al. <ref>Driell, D. Van; Provis, J.M.; Billson, F.A.: Early differentiation of ganglion, amacrine, bipolar and Muller cells in the developing fovea of the human retina. J. Comp. Neurol. 291: 203-219.</ref> studied the manner in which amacrine, bipolar, retinal ganglion cells, and Muller cells differentiate in the developing fovea of the retina of a 15-week old human foetus. <ref name="PMID1628748"><pubmed>1628748</pubmed></ref> Tripathy also published an article providing evidence that the lacrimal glands in humans originates from the neuroectoderm. <ref name="PMID2406219"><pubmed>2406219</pubmed></ref>

|}

==Development, Structure and Function of Ocular Components==

The eye itself is formed from several components; notably the optic placode of the head ectoderm, the optic vesicle from the neural tube, and mesenchyme from the mesoderm and neural crest cells. The optic placode contributes the lens to the eye, the optic vesicle gives rise to layers of the retina, while the mesenchyme will produce the ciliary body, iris, choroid and sclera.<ref>http://www.vetmed.vt.edu/education/curriculum/vm8054/eye/EMBYEYE.HTM</ref> Cells from the neural tube will also produce the optic nerve, which receives nerve impulses from the retina of the eye. Eyes initially form as laterally paired structures and migrate medially in the human embryo. In other animals such as birds and lizards, the eyes do not migrate and develop laterally on the head. The optic placodes become prominent on the surface of the embryo at approximately Stage 14 of development.

[[File:Stage14 sem2b-limb.jpg|200px|thumb|left|A Stage 14 embryo showing the location of an otic placode.<ref name="http://embryology.med.unsw.edu.au/embryology/index.php?title=ANAT2341_Lab_6_-_Early_Embryo">http://embryology.med.unsw.edu.au/embryology/index.php?title=ANAT2341_Lab_6_-_Early_Embryo</ref>]] [[File:Stage 13 image 060.jpg|400px|thumb|center|A cross section showing the organisation of the developing brain, the optic vesicle and the lens (optic) placode.<ref name="http://embryology.med.unsw.edu.au/embryology/index.php?title=ANAT2341_Lab_6_-_Early_Embryo"/>]]

===Optic Nerve===

The optic nerve consists of nerve fibres that transmit information from the retinal photoreceptor cells to the brain. The optic nerve is formed from the optic stalk, which develops as the optic vesicle migrates from its origin in the neural tube to its destination - the surface ectoderm - where it will fuse with the optic placode (also known as the lens placode, which will contribute the lens to the eye).<ref name="PMID11687490"><pubmed>11687490</pubmed></ref>

[[File:Formation of the optic vesicle 1.jpg|400px|thumb|left|Fig. 1: Early formation of the optic vesicle from the neural groove.]] [[File:Formation of the optic vesicle 2.jpg|400px|thumb|center|Fig. 2: The optic vesicle at a later stage, showing the optic stalk.]]

As can be seen in Figure 1 above, the optic vesicle forms from the neural tube. However, note that the neural tube has not yet closed, and is still the neural groove at this point. Figure 2 then shows the optic vesicle at slightly later stage in the same simplified cross-section of the embryo, as it migrates from the neural tube to the surface ectoderm. Note the presence of the optic stalk which links the optic vesicle to the neural tube. Later in development, this primitive structure will become the optic nerve, which will link the eye to the brain.

The nerve fibres themselves will initially originate from the retinal ganglion cells in the eye during week 6.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008">Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008</ref> After two weeks, these fibers will have grown along the inner wall of the optic stalk and have reached the brain. They grow both in length and width, with the nerve fibres filling the hollow optic stalk to form the solid optic nerve. More than one million nerve fibers will eventually make up the optic nerve, along with glial cells which arise from the inner wall of the optic stalk itself.<ref><pubmed>1451666</pubmed></ref> Myelinisation of the optic nerve begins much later in development at around 7 months, beginning at the optic chiasm and moving towards the eye.<ref><pubmed>7224936</pubmed></ref> The optic chiasm forms just before the nerves reach the brain, and is where half the nerve fibres from each eye will cross over to the opposite side of the brain. This is demonstrated in Figure 3. Note the crossing over of the optic nerves just before they enter the brain, at the optic chiasm. This organisation is now much more familiar, with the eyes near the ectoderm and the optic nerve leading through the mesoderm to the brain buried deep in the embryo.

[[File:Formation of the optic nerve and chiasm 1.jpg|400px|thumb|center|Fig. 3: A recognisable brain and eye structure in later development.]]

===Retina===

The retinal component of the eye is formed when the optic vesicle folds in upon itself, forming the optic cup (see Figure 4). In doing so it creates two layers - an inner wall and an outer wall of the optic cup (Figure 5). These two layers of the optic cup will give rise to the two layers of the retina - the inner neural retina, and the outer pigmented epithelium.<ref name="PMID11687490"/> Note the existence of the space between the two layers of the retina. This is known as the intraretinal space and disappears by the 7th week of development, however the two layers never completely fuse and can become separated as a result of physical trauma to the head - leading to a detached retina and loss of vision.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/>

The inner wall of the optic cup, which will give rise to the neural retina, consists of a layer of pseudostratified cells (see Figure 6) that later differentiate into rod, cone, bipolar, ganglion, horizontal, amacrine and glial cells of the retina (Figure 7).<ref name="PMID18168748"><pubmed>18168748</pubmed></ref> The outer wall of the optic cup consists of a layer of cuboidal cells that contain melanin - the light absorbing pigment. The function of this layer is to absorb light and prevent internal reflection of light within the eye, which would impair our ability to form distinct images. Interestingly, in some animals such as cats, this layer actually reflects light intentionally to increase the amount of light available to the eye in low-light conditions. This is why cats seem to have eyes that glow in the dark.<ref>http://dialspace.dial.pipex.com/agarman/bco/fact4.htm</ref>

[[File:Formation of the optic cup 1.jpg|400px|thumb|left|Fig. 4: Mechanism of optic cup formation.]] [[File:Formation of the optic cup 2.jpg|400px|thumb|center|Fig. 5: Layers of the optic cup in retina development.]]

The inner wall itself is divided into two components - the inner neuroblastic layer and the outer neuroblastic layer (see Figure 6). The outer neuroblastic layer forms the rod and cone cells while the inner neuroblastic layer forms the remaining cell types found in the retina - the bipolar, ganglion, horizontal, amacrine and glial cells (Figure 7).<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/> The organisation of the retina is interesting in that incoming light passes through several layers of these neural retina cells before it is detected by rod and cone cells at the back of the retina, and then nerve signals are passed back through the layers of neural retina cells that the light just passed through moments before - a seemingly strange design that the eye does not share with man-made light-capturing devices such as a camera (imagine putting the wires in front of the image sensor!).

Differentiation of the neuroblastic layers into neural retina cells occurs in a pattern both within the layers and across the retina. Cells differentiate from the inner neuroblastic layer to the outer neuroblastic layer, and differentiate from the central retina to the peripheral retina.<ref name="PMID18168748"/> The macula is first identifiable in week 22 when ganglion cells start to form multiple rows, and the primitive fovea begins to form at approximately the same time as a depression in the macula.<ref><pubmed>6462623</pubmed></ref> It is not until 15-45 months after birth that this area becomes exclusively populated by cone cells and becomes the fovea centralis - the area of the retina with the highest visual acuity.

[[File:Formation of the retina 1.jpg|400px|thumb|left|Fig. 6: Cross-section of the primitive retina showing cell types and layers.]] [[File:Formation of the retina 2.jpg|400px|thumb|center|Fig. 7:Cross-section of a developed retina showing cell types and layers.]]

===Ciliary Body===

The ciliary body consists of ciliary processes and three portions of fibres that constitute the ciliary muscles. It functions to maintain normal eye physiology as well as playing a direct role in accommodation.

During development, the ciliary processes form slightly posterior to the iris, developing from part of the anterior rim of the optic cup. It is thought that the folded structure of the ciliary processes is brought about by intraocular pressure and specific signalling pathways.<ref name="PMID16959249"><pubmed>16959249</pubmed></ref> While the ciliary muscles and the endothelial cells of the ciliary blood vessels are chiefly formed by mesenchymal cells<ref><pubmed>16249499</pubmed></ref>, the neural crest and neuroectoderm also contribute to their development.<ref><pubmed>12127103</pubmed></ref> The normal development of the ciliary body is dependent on the correct expression of bone morphogenetic protein (BMP)-4, which is a member of the transforming growth factor-β superfamily.<ref><pubmed>1222340</pubmed></ref> Napier and Kidson (2007) summarised numerous genes that have been associated with ciliary body development, however their direct roles have not been well documented.<ref name="PMID16959249"/>

===Iris===

The iris is a thin layer that develops at the end of the third month of development and is derived from the anterior rim of the optic cup. The stroma of the iris develops from cells of neural crest cell origin.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/> The muscles that are responsible for the dilation and constriction of the pupil (dilator pupillae and sphincter pupillae muscles) form from the neuroectoderm of the optic cup. These cells are initially epithelial cells that then transform into smooth muscle cells. <ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"></ref>. The invagination of the optic vesicle which creates the optic cup, also causes the formation of the optic cup lip. This is the region of the where the epithelium doubles back, separating the outer pigmented layer and the inner nonpigmented layer. This is the edge of the iris that borders on the pupil<ref><pubmed> Retinal and anterior eye compartments derive from a common progenitor pool in the avian optic cup</pubmed></ref>.

The final colour of the iris is not evident until the postnatal period. It is determined by a number of genes including IRF4, SLC24A4 and MATP<ref><pubmed>19710684</pubmed></ref>. Other features such as crypt frequency, furrow contractions, presence of peripupillary pigmented ring, and number of nevi also become evident during development<ref><pubmed>21835309</pubmed></ref>. Mutations in Pax6 have been shown to cause partial or complete loss of the iris <ref><pubmed>12386935</pubmed></ref>.

===Cornea===

The cornea is the transparent, avascular, most anterior portion of the eye. It is responsible for conducting light into the eye and focusing it on to the retina, as well as maintaining the rigidity of the eyeball. It consists of 5 layers- the epithelium, Bowman’s layer, stroma, Descemet’s membrane and the endothelium.

The epithelium and endothelium of the cornea first appear during the 5th week of gestation. The epithelium of the external surface of the cornea is derived from surface ectoderm, while the mesenchyme is derived from the mesoderm<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"/>. The endothelium is a two-cell cuboidal layer which is made up of differentiated neural crest cells that were initially from the optic cup. By week 8 the endothelial cells begin to secrete a basement membrance which later forms Descemet’s membrane<ref><pubmed>6511224</pubmed></ref>. At approximately 16 weeks gestation the Bowman’s membrane begins to form from the thickening of the stroma that is located under the corneal epithelium<ref>Riordan-Eva P, Whitcher JP. Vaughn and Asbury's General Ophthalmology, Lange Medical Books/McGraw Hill. 2004:25–27</ref>. During the third month glycosaminoglycans secreted by fibroblasts form the ground substance of the cornea, with collagen fibrils and keratan sulphate also appearing around this time. Shortly after this tight junctions form between the endothelial cells<ref><pubmed>19481138</pubmed></ref>. Fibroblast growth factor causes the epithelial cells to proliferate<ref><pubmed>20105280</pubmed></ref>.

Towards the end of the gestational period the cornea becomes larger due to the production of aqueous humor<ref>Yanoff M, Duker JS. Ophthalmology. Mosby; St. Louis, MO: 2004</ref>. The final transparent structure develops because hyaluronidase removes hyaluronic acid, thyroxine causes dehydration of the stroma, and the entire structure becomes avascular<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/>. Numerous genes have been implicated in the development of the cornea, these include, but are not limited to, PAX6, PITX2, FOXC1, MAF, TMEM114, SOX2, OTX2 and BMP4<ref><pubmed>18637741</pubmed></ref>. Pax6 and Pax6(5a) isoforms are essential for the normal development of the eye. Over or under expression can both lead to major structural abnormalities<ref><pubmed>18386822</pubmed></ref>.

===Lens===

The lens has its origin from the optic placode, which develops on the ectodermic surface of the embryo and migrates both medially and inwards into the embryo. The lens allows accommodation of the eye, and adjusts its thickness in order to focus on near or far objects. The study of lens development was one of the first to highlight the importance of inductive signaling in development, with Spemann's pioneering work at the start of the 20th century, finding that the absence of retinal development resulted in the absence of lens formation.<ref name="PMID11687490"/> Indeed, it has been consistently shown that the interaction of the migrating optic vesicle with the surface ectoderm of the head is vital in producing differentiation of the lens.<ref name="PMID15558475"><pubmed>15558475</pubmed></ref> The mechanism of interaction is complex but basically involves upstream genes switching on downstream genes, with the genes eventually producing specialised proteins which constitute the lens. The whole process starts with the signaling molecules from the optic cup initiating a thickening of the surface ectoderm of the head (Figure 8). It is thought that this region of specific ectoderm is responsive to the signaling molecules, as lens formation is incomplete or absent when ectoderm from the lateral portion of the embryo (i.e. non-head ectoderm) is exposed to the same inductive signaling processes.<ref name="PMID9216064"><pubmed>9216064</pubmed></ref> Pax6 has been shown to be one of the major genes required for differentiation of the lens, which in turn switches on transcriptional genes such as Sox 1, 2 and 3 among others - producing water-soluble proteins called crystallins - responsible for giving the lens its transparency and refractive properties.<ref name="PMID9609835"><pubmed>9609835</pubmed></ref>

[[File:Formation of the lens 1.jpg|400px|thumb|left|Fig. 8: The importance of the optic cup in lens differentiation.]] [[File:Formation of the lens 2.jpg|400px|thumb|center|Fig. 9: The lens placode separates from the ectoderm and migrates into the mesoderm forming the lens vesicle.]]

The lens placode invaginates from the head ectoderm and migrates into the mesoderm (Figure 9). Once this structure (now known as the lens vesicle) is in place opposite the optic cup, the combined structure is referred to as the optic globe and resembles a recognisable eye structure. The lens continues to differentiate further, as mentioned above, through the formation of crystallin proteins, which give the lens its unique properties and allows for the fine control over the degree of refraction that takes place.

===Aqueous Chambers===

There are both anterior and posterior aqueous chambers of the eye which contain aqueous humour. A space develops in the mesenchyme situated between the lens and cornea to form the anterior aqueous chamber. The mesenchyme located superficially to this chamber forms the mesothelium as well as the transparent portion of the cornea.

The posterior chamber develops from a similar space in the mesenchyme, however it is located between the iris and the lens. The anterior and posterior chambers are able to communicate with one another once the papillary membrane vanishes and the pupil is formed. This channel is known as the scleral venous sinus.<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011">Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011</ref>

Contained within the aqueous chambers is aqueous humor. The production of aqueous humor is dependant on the development of the ciliary body. It is produced in the ciliary processes and it’s production is a metabolic process driven by the delivery of oxygen and the removal of wastes via the ciliary circulation<ref><pubmed>20801226</pubmed></ref>.

===Choroid and Sclera===

The choroid and sclera are adjacent layers that surround the eye and act to vascularise and protect the eye respectively. They are formed from neural crest and mesoderm-derived mesenchyme which condenses around the optic cup and lens vesicle between weeks 5 and 7 of development to form a primitive eyeball structure known as the optic globe.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/> Blood vessels first start to appear in the choroid layer at approximately week 15, and arteries and veins can be distinguished by week 23.<ref>Development of the Choroid and Related Structures, K. Sellheyer, Eye (1990) 4, 255-261</ref> Inductive processes are thought to play a vital role during formation of the choroid and sclera; with the retinal pigmented epithelium inducing differentiation of the surrounding mesenchyme while at the same time the neural crest-derived mesenchyme contributing components to the retinal pigmented epithelium such as melanocytes.<ref name="PMID1628748"/> In addition to having functional roles themselves, the primitive choroid and sclera also contribute components to the developing ciliary body and cornea (Figure 10). In the adult eye, the choroid is continuous with the ciliary body and the sclera with the cornea.

[[File:Formation of the choroid and sclera 1.jpg|400px|thumb|center|Fig. 10: The choroid and sclera derives from mesenchyme surrounding the optic cup.]]

===Eyelids===

The eyelids are ectodermal and mesodermal in origin and are an extension of the skin which covers and protects the eye. The surface ectoderm gives rise to the conjunctiva, skin epithelium, hair follicles, cilia, Zeis glands, glands of Moll, and meibomian glands. <ref name=" Cook CS, Ozanics V, Jakobiec FA. (1994) Prenatal development of the eye and its adnexa. In Tasman W, Jaeger EA, editors: Duane’s foundations of clinical ophthalmology, vol 1, Philadelphia, 1994, Lippincott. "> Cook CS, Ozanics V, Jakobiec FA. (1994) Prenatal development of the eye and its adnexa. In Tasman W, Jaeger EA, editors: Duane’s foundations of clinical ophthalmology, vol 1, Philadelphia, 1994, Lippincott. </ref> The mesenchyme gives rise to the tarsal plates, levator muscles, orbicularis muscles, and tarsal muscle of Muller. <ref name=" Cook CS, Ozanics V, Jakobiec FA. (1994) Prenatal development of the eye and its adnexa. In Tasman W, Jaeger EA, editors: Duane’s foundations of clinical ophthalmology, vol 1, Philadelphia, 1994, Lippincott. "/> Eyelid formation can be first noted during week 5 when small grooves develop in the surface ectoderm (Figure 11).<ref><pubmed>7364662</pubmed></ref> These small grooves deepen and extend into the mesoderm and the primitive eyelid structures grow towards one another, eventually fusing together during week 8.<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"/> It is not until week 26-28 that the eyelids will separate again. The anterior surface of the eyelid becomes covered by two layers of epithelium; this forms the epidermis of the eyelids. <ref name="Kikkawa DO, Lucarelli MJ, Shovlin JP, et al: Ophthalmic facial anatomy and physiology. In Kaufman PL, Alm A, editors: Adler’s physiology of the eye, St Louis, 2003, Mosby, pp 16."> Kikkawa DO, Lucarelli MJ, Shovlin JP, et al: Ophthalmic facial anatomy and physiology. In Kaufman PL, Alm A, editors: Adler’s physiology of the eye, St Louis, 2003, Mosby, pp 16.</ref> Tarsal plates then begin to develop, which eventually leads to the formation of meibomian glands. <ref name="PMID1628748"/> The ectoderm reflects over the developing cornea to form the conjunctival sac, a space that is filled by secretions from the lacrimal gland in order to allow smooth motions of the eyelid over the eye and also to clean the cornea and prevent accumulation of particles on the eye that may disrupt vision. By the time the eyelids separate, the eye has all its major components present (Figure 12), and further development consists mainly of growth and vascularisation.

[[File:Formation of the eyelid 1.jpg|400px|thumb|left|Fig.11: Small grooves in the ectoderm of the head - the precursors to an eyelid.]] [[File:Formation of the eyelid 2.jpg|400px|thumb|center|Fig. 12: The eye at an advanced stage of embryonic development. Note however, that the eyelids remain fused until much later.]]

===Lacrimal Glands===

There are three stages of lacrimal gland development. The first is the presumptive glandular stage in which the superior conjunctival fornix epithelium thickens and the surrounding mesenchymal cells condense. These mesenchymal cells are of neural crest origin<ref><pubmed>9882499</pubmed></ref>. The second stage sees the development of nodular formations around the superior conjunctival fornix and the formation of lumina within the epithelial buds, this stage is therefore known as the bud stage. Innervation and vascularisation also occur during this stage. The final morphological changes occur during the glandular maturity stage which occurs in weeks 9-16 when the lacrimal glands begin to resemble the mature glands. During the 13th week the lacrimal and zygomatic nerves anastomose<ref><pubmed>14635806</pubmed></ref>.

These glands are responsible for the production of tears however they do not start to function until 1-3 months after birth. The mature lacrimal gland is made up of two lobes- the palpebral and orbital lobes.

==Current Research==

Not only are there still many important processes and components of eye development that we would like to understand, this knowledge also contributes to the development of treatments for eye disorders and technologies such as the bionic eye.

===The impact of visible light on the immature retina===

<pubmed>22405869</pubmed>

The authors mentioned in this article <ref name="PMID22405869"><pubmed>22405869</pubmed></ref> that they were interested in investigating the effect of light on postnatal eye development in mice, because mice are born with fused eyelids, which separate 12 days after birth. Before the eyelids separate, the retina develops in mice with very little radiation from light. It is believed that the darkness plays a role in the development of the retina in mice, which is why their eyelids are fused for 12 days after birth. Therefore the authors were interested to see what effect light would have on postnatal retinal development of mice, with special interest in retinal ganglion cells (RGC). In their experiment, they surgically opened the eyelids on the right eyes of some of the mice to expose them to visible light 12 hours per day, while they left some other mice in the dark after surgical separation of their eyelids. They also kept the left eyes of the mice naturally fused as controls in the experiment. Their results showed that early light exposure in mice causes a decrease in retinal ganglion cells because it affects cellular apoptosis in the retina. The authors also observed that early exposure to light in mice causes lumican mRna transcription to resume and to quickly increase. (Lumican normally stays silent in retina after birth).

---------

===GABA Maintains the Proliferation of Progenitors and Non-Pigmented Ciliary Epithelium===

<pubmed>22590629</pubmed>

{| width=800px
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| width=450px|
| width=350px|

|-
| GABA is an ‘inhibitory neurotransmitter’ in the central nervous system of adults. <ref name="PMID22590629"><pubmed>22590629</pubmed></ref> It is responsible for controlling proliferation of stem cells and progenitor cells. The authors of this article <ref name="PMID22590629"/> was interested to find the effects of GABA on proliferation of progenitor cells and non-pigmented ciliary epithelial cells (NPE) in the retina. Their study focused on progenitor cells and non-pigmented epithelium of the ciliary body in chickens. Non-pigmented epithelial cells in chickens arise from the neuroepithelium of the optic cup. They share similar functions as progenitors of the early retina, such as expression of Chx10 and Pax6 genes. It is not agreed upon whether epithelial cells of the ciliary body have stem cell properties. However, it has been found that these cells can be cultured and transplanted into retinas that are injured, in order to replace neurons that were previously lost. However, there is not much known about what factors regulate the proliferation of stem cells. Hence the authors were interested in finding the effects of GABA on proliferation of retinal cells. Their results showed that non-pigmented epithelial cells in chickens ‘express extrasynaptic-like GABAA receptors’ that have the ability to regulate cell proliferation. It has been found that inhibiting these ‘GABAA receptors’ also causes a decrease in proliferation of retinal progenitor cells and non-pigmented epithelial cells in 'the intact E8 retina’. <ref name="PMID22590629"/>

|
[[File:Gaba-effects-retina.JPG|thumbnail|250px|'''GABAA receptor mediated effects on retinal progenitor cell proliferation'''
]]
|}

-------------------------

===Stem Cells===

[http://www.advancedcell.com/patients/clinical-trial-information/ Advanced Cell Technology]- A biotechnology company which is currently running two clinical trials that utilise human embryonic stem cell derived retinal pigmented epithelial cells. These trials are examining the possibility of using these cells to treat stargardt's macular dystrophy and dry age-related macular degeneration<ref><pubmed>22281388</pubmed></ref>.

-------------------

===MIP/Aquaporin 0 Represents a Direct Transcriptional Target of PITX3 in the Developing Lens===

<pubmed>21698120</pubmed>

{| width=800px
|-
|PITX3 plays a siginificant role in the development of lens in vertebrates. If there is a deficiency is PITX3, it causes a range of problems in humans such as microphthalmia, Peter’s anomaly, or isolated cataracts. Mutation of PITX3 also causes degeneration of the lens in zebrafish and mice. It is therefore important to understand what factors may affect the decrease in PITX3, as a normal level of PITX3 is needed to maintain normal eye development. The authors wanted to investigate specific genes which are affected by PITX3. Previous research has shown that MIP and Aquaporin causes defects in the lens in both mice and humans. MIP and Aquaporin are targeted by PITX3, so their imbalance is interrelated in the cause of defects in the lens. Therefore it has been previously proven that PITX3 is needed for normal development of the lens. However, there has not been much information previously known regarding the exact effect that PITX3 has, or the specific genes it targets. Since MIP and Aquaporin is common genes found in humans, mice and zebrafish, the authors <ref name="PMID21698120"><pubmed>21698120</pubmed></ref> chose to study these genes to understand the pathway that PITX3 takes and its exact involvement in the development of the lens. Their results proved that deficiency in MIP and Aquaporin indeed affects normal development of the lens, and it is indeed related to deficiency in PITX3. However, there is still more research needed to understand PITX3 and the genes it interacts with, and their effect in ocular development.

|
[[File:Mip1-expression-in-pitx3.jpg|thumbnail|250px|'''Analysis of mip1 expression in pitx3-mo and control embryos via in situ hybridization and RT-PCR''']]
|}

-------------------

===Activation of c-Jun N-terminal kinase (JNK) during mitosis in retinal progenitor cells.===

<pubmed>22496813</pubmed>

{| width=800px
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| In the past, most studies about c-Jun N-terminal kinase (JNK) in the retina have been in relation to neurodegeneration. <ref name="PMID22496813"><pubmed>22496813</pubmed></ref> Therefore the authors in this article were interested in investigating the function of c-Jun N-terminal kinase in the retinal progenitor cells in neonatal rats. <ref name="PMID22496813"/> In the experiment, they took retinal tissue from newborn rats and fixed them, and subsequently examined them using confocal microscopy and fluorescence to discover c-Jun N-terminal kinase ‘phosphorylation by immunohistochemistry’. <ref name="PMID22496813"/> Mitotic cells in the retina were identified during the experiment. The results of their experiment revealed that c-Jun N-terminal kinase is phosphorylated in the developing retina of neonatal rats during the mitosis of progenitor cells. <ref name="PMID22496813"/> This shows that c-Jun N-terminal kinase can control the proliferation of progenitor cells in the developing retina. Their experiment also revealed that inhibiting c-Jun N-terminal kinase causes disruptions to the mitotic cell cycle by reducing the cell numbers in anaphase. <ref name="PMID22496813"/> However, inhibiting c-Jun N-terminal kinase did not change the cell numbers in metaphase or prophase. <ref name="PMID22496813"/>

|
[[File:JNK1.png|thumbnail|300px|'''"JNK is phosphorylated during mitosis of retinal progenitor cells."''']]
|}

----------------------------

===LRP5 is required for vascular development in deeper layers of the retina===

<pubmed>20652025</pubmed>

{| width=800px
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|
The lipoprotein receptor-related protein 5 (LRP5) has a significant function in the development of retinal vasculature.<ref name="PMID20652025"><pubmed>20652025</pubmed></ref> Research has shown that mutations of the LRP5 causes loss of function, due to incomplete development of retinal vessel network, in both humans and mice. The authors investigated how mutations occur in the LRP5, which leads to abnormal development of the retinal vasculature. They have studied retinal endothelial cells in mutant mice in their study. Their results showed that in retina with mutated LRP5, endothelial cells in the retinal vasculature primarily produced cell clusters in the inner-plexiform layer instead of migrating into deeper layers of the retina to form normal retinal vasculature. The authors also discovered that there was a decrease in Slc38a5, which is “a Müller cell-specific glutamine transporter”, in mice with mutated LRP5. Their results lead the authors to conclude that normal LRP5 is very important in the development of normal retinal vasculature due to their role in causing migration of retinal endothelial cells in the deeper layers of the retina. LRP5 is also important for retinal interneurons and Müller cells to function correctly.

|
[[File:Retina-cell-clusters.JPG|350px|thumbnail|'''Endothelial cells form thick clusters in the LRP5 mutant retina''']]
|}

-----------------

===Astrocyte-Derived Vascular Endothelial Growth Factor===

<pubmed>20686684</pubmed>

{| width=800px
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|
Vascular endothelial growth factor (VEGF) has an important role in normal development of retinal vasculature. <ref name="PMID20686684"><pubmed>20686684</pubmed></ref> In the process of vascularisation of the retina, the retinal astrocytes (both vascularised and not yet vascularised) expresses the vascular endothelial growth factor. <ref name="PMID20686684"/> This fact indicates that vascular endothelial growth factor that are derived from astrocytes of the retina plays an important role in vessel maturation and angiogenesis. <ref name="PMID20686684"/> Therefore the authors wanted to test the role of vascular endothelial growth factor that are derived from astrocytes to find further confirmation. ‘Cre-lox technology’ was used in the experiment to remove the vascular endothelial growth factor from mice retinal astrocytes in the developmental period. <ref name="PMID20686684"/> The results showed that removing vascular endothelial growth factor that are derived from astrocytes caused ‘the regression of smooth muscle cell-coated radial arteries and veins’ from the effects of hyperoxia. <ref name="PMID20686684"/> Hence, this result indicates that vascular endothelial growth factor plays an important role in stabilising blood vessels during the development of the retinal vasculature. <ref name="PMID20686684"/> It has been suggested that this finding may be of relevance to retinopathy in premature neonatal humans. <ref name="PMID20686684"/>

[[File:Astrocyte-vegf-deletion.JPG|250px|thumbnail|'''"Astrocyte specific deletion of VEGF." ''']]
|
[[File:Effect-of-vegf-on-retinal-vasculature.JPG|250px|thumbnail|'''"Effects of astrocyte-derived VEGF on retinal vascular development."''']]
[[File:Vegf-protects-vessels.JPG|250px|thumbnail|'''Astrocyte-derived VEGF protects vessels from hyperoxia. ''']]

|}

==Useful Links==

{{External Links}}

[http://www.youtube.com/watch?v=Xme8PA6xv-M Visualisation of eye development in the embryo]

[http://www.embryo.chronolab.com/sense.htm Embryonic Development of the eye]

==Glossary==

'''Accommodation''' - changing the focal length of the lens in order to focus on an object.

'''Downstream genes''' - genes that are activated by other "upstream genes".

'''Ectoderm''' - outermost layer of germ cells in an early embryo.

'''Endoderm''' - innermost layer of germ cells in an early embryo.

'''Glial cells''' - non-neuronal cells that provide structure and protection to neurons as well as producing myelin.

'''Inductive signaling''' - a process whereby the secretion of factors from one cell or tissue triggers a response in another.

'''Lens vesicle''' - the cavity of invaginated ectoderm from the optic placode that will form the lens.

'''Macula''' - a highly pigmented, oval-shaped area located near the centre of the retina. Important for visual acuity.

'''Mesenchyme''' - undifferentiated, loose connective tissue.

'''Mesoderm''' - middle layer of germ cells in an early embryo.

'''Mesothelium''' - the epithelial layer of the mesoderm.

'''Myelinisation''' - development of a myelin sheath around a nerve fibre.

'''Neural crest''' - a portion of the ectoderm situated next to the neural tube.

'''Neural groove''' - a large invagination on the dorsal surface of the embryo which will close off and form the neural tube.

'''Neural tube''' - hollow structure that results from the folding of the neural plate and eventually forms the central nervous system.

'''Neuroblastic layer''' - a layer of immature cells that differentiate to form either glial cells or neurons. The retina has two of these (an inner and outer).

'''Neuroectoderm''' - portion of the ectoderm that develops to form the central and peripheral nervous systems.

'''Optic chiasm''' - the point at which the optic nerves meet and cross over.

'''Optic cup''' - the structure that is formed after the optic vesicle folds in upon itself. This will form the retina.

'''Optic globe''' - a term that refers to the optic cup, lens vesicle and surrounding mesenchyme collectively.

'''Optic placode''' - area of thickened ectoderm that gives rise to the lens of the eye.

'''Optic stalk''' - a long, narrow cavity that will produce the optic nerve.

'''Optic vesicle''' - a cavity that buds off from the neural tube and gives rise to the optic cup.

'''Upstream genes''' - genes that activate one or more other "downstream genes".

'''Vascularise''' - to invade with blood vessels.

==Image Gallery==
<gallery>
Image:Eye_diagram_bandw.jpg‎ | Basic structure of the human eye.
Image:Stage14 sem2b-limb.jpg | A Stage 14 embryo showing the location of an otic placode.
Image:Stage 13 image 060.jpg | A cross section showing the organisation of the developing brain, the optic vesicle and the lens (optic) placode.
Image:Formation of the optic vesicle 1.jpg | Early formation of the optic vesicle from the neural groove.
Image:Formation of the optic vesicle 2.jpg | The optic vesicle at a later stage, showing the optic stalk.
Image:Formation of the optic nerve and chiasm 1.jpg | A recognisable brain and eye structure in later development.
Image:Formation of the optic cup 1.jpg | Mechanism of optic cup formation.
Image:Formation of the optic cup 2.jpg | Layers of the optic cup in retina development.
Image:Formation of the retina 1.jpg | Cross-section of the primitive retina showing cell types and layers.
Image:Formation of the retina 2.jpg | Cross-section of a developed retina showing cell types and layers.
Image:Formation of the lens 1.jpg | The importance of the optic cup in lens differentiation.
Image:Formation of the lens 2.jpg | The lens placode separates from the ectoderm and migrates into the mesoderm forming the lens vesicle.
Image:Formation of the choroid and sclera 1.jpg | The choroid and sclera derives from mesenchyme surrounding the optic cup.
Image:Formation of the eyelid 1.jpg | Small grooves in the ectoderm of the head - the precursors to an eyelid.
Image:Formation of the eyelid 2.jpg | The eye at an advanced stage of embryonic development. Note however, that the eyelids remain fused until much later.

</gallery>

==References==
<references/>

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--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

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{{2012Projects}}

User:Z3254758

2012-10-03T00:11:36Z

Z3254758: /* Lab Attendance */

==Lab Attendance==

--[[User:Z3254758|Z3254758]] 10:04, 25 July 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:35, 1 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:09, 8 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:04, 15 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:15, 22 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:05, 29 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 11:08, 12 September 2012 (EST) arrived at 10:10am

--[[User:Z3254758|Z3254758]] 10:02, 19 September 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:07, 26 September 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:11, 3 October 2012 (EST)

==Lab 1==

<pubmed>22178154</pubmed>

This article reviews some important features of capacitation as well as presenting their findings regarding the role of PLD-dependent actin polymerization in sperm motility during capacitation. They demonstrated the importance of PLD-dependent actin polymerization for developing hyper-activated motility.

==Lab 2==

{|
|-
|'''Task 1'''

|-
|[[File:Paternal_chromatin_mouse_embryos.jpg|thumb|left]]

|-
|'''Task 2'''

|-
|Rac1 and RhoA are Rho GTPases that regulate the invasion of the human embryo through the endometrial stroma. Inhibition of Rac1 expression prevents embryo invasion of the stroma, whereas inhibition of RhoA promotes it. Rac1 also plays a role in human endometrial stromal cell migration.

<pubmed>PMC2562412</pubmed>
|}

==Lab 3==

1. Gestational age refers to the time period between the first day of the mothers last period and birth. Fertilisation age is the time between conception and birth. <ref><pubmed>15520122</pubmed></ref>.

==Lab 4==

1.

Amniocentesis- involves using a needle to take a sample of amnitoic fluid. It can be used to detect down syndrome and turner syndrome among other abnormalities.

Chorionic villus sampling- a needle is used to take a sample of chorionic villus (placental tissue). It is helpful in detecting down syndrome and cystic fibrosis.

2.

<pubmed>3240835</pubmed>

This paper demonstrates the successful use of intrathecally injected mesenchymal cells derived from human umbilical cord blood to partially recanalise a dissected basilar artery. The patient was a 17 year old Korean man with infarction of the bilateral pons, midbrain and right superior cerebellum as a result of the basilar artery dissection.

The paper identifies that human umbilical cord blood contains hematopoietic stem cells, as well as mesenchymal stem cells which express neural makers Tuj1, TrkA, glial fibrillary acidic protein and cyclic nucleotide phosphodiesterases.

As a result of his condition the patient became quadriplegic, was unable to speak, and was unable to move his eyes, as well as a number of other symptoms. His clinical symptoms were visibly improved 5 days after the initial treatment with the mesenchymal cells. After the 27th day of treatment he regained his gag reflex, was able to swallow, had pupil dilation and was able to move his eyes, his soft palate stopped sagging, and the rigidity of his muscle tone reduced enough to allow him to sit in a wheelchair.

==Lab 7==

1.Provide a one sentence definition of a muscle satellite cell (b) In one paragraph, briefly discuss two examples of when satellite cells are activated ?

Satelite cells are stem cells that are located under the basal laminar of each muscle. When muscle is damaged satelite cells infiltrate the muscle and repair or replace it. They are normally quiescent.

2.In one brief paragraph, describe what happens to skeletal muscle fibre type and size when the innervating motor nerve sustains long term damage such as in spinal cord injury?

==Lab 8- Peer Review==

'''Group 2- Somatosensory'''

-Great introduction. Really puts the project in context and justifies the importance of your research. Citations need to be formatted like the rest of the page

-History of discoveries-very poor syntax, word repetition and no paragraphs. What is Weber's full name? This is entitled "history of discoveries" when it is actually just a very brief, nonspecific summary of "Weber". What about the other interesting discoveries from various scientists over decades?

-Adult Central Somatosensory systems- ascending in what? Position? Importance? Activity? Sensitivity? This needs a more informative opening sentence.

-Trigeminal system and Development of the Primary Somatosensory Cortex- are well explained and ideas are presented in a logical, flowing manner. Great picture with a good description and referencing (impressed you drew it).

-"making connections between...." what do the stages mean? Why does it start at stage 23 instead of stage 1?

-touch/touch receptors is good but where are the references?

-pain and pressure sections also good but needs paragraphs and the formatting of citations is incorrect

-bullet points in pressure section need a brief sentence introducing their purpose. Papers listed at bottom of section should be correctly cited instead of having hyperlinks

-interesting info in temperature

-current research- maybe you could put the name of the paper and authors and explain how they conducted their study? That would help with understanding the nice picture

-Glossary is incomplete

-Needs more pictures

-minor grammatical and spelling errors throughout but overall very good and well sequenced.

'''Group 3- Taste'''

Overall this is an excellent project. Well written, great informative photos, good use of tables, and comprehensive information that's well explained.

A few of the photos don't have the appropriate copyright information and some sections of text haven't been referenced, but in general this ticks all of the boxes

'''Group 4- olfaction'''

-numerous typos and syntax errors throughout. My favourite is "naval cavity"

-generally well explained and I like how you've used different formats for each section to keep it interesting

-this seems a bit random-

"SINUSES: A:
EFFECT OF AMNIOTIC FLUID ON THE DEVELOPMENT OF OLFACTION IN THE FETUS (current research in the field):"

-I think the anatomy section should come before the developmental timeline just to put the developmental stages in context

-abnormal function is very comprehensive :)

-current research is great, it appears some quality research went into this

-excellent use of resources throughout, including your external links. I think you've covered everything well

'''Group 5- abnormal vision'''

-content of introduction is good and immediately puts the page in context. Emphasises abnormal development. Perhaps reconsider the syntax of some of the sentences

-paragraphing throughout project needs review

-a picture near the beginning would make the page more engaging. Seeing you can't talk too much about normal eye development, it might help in conveying some information

-you frequently make use of the carnergie stages, which is great, but perhaps briefly describe what this system means

-it's good that you have contrasted normal and abnormal development for each structure, but make sure the information isn't repeated in the "normal development" section, or perhaps remove that section altogether

- info about what the different genes control is good. What does "the first embryonic days 8.5" mean?

-I assume the two separate sections in "ocular manifestations" are genetic and environmental, but because they're not stated in the intro of this section and there's so much information in-between, it's difficult to tell. The formatting of this section adds to the confusion. Keeping the information and formatting consistent for each abnormality will make this easier to follow. The appropriate heading, sub-heading etc formatting needs to be used as well

-I like your case study, it reminds us of how these problems effect real people

-no current research or external links section?

-excellent use of resources

'''Group 6-Hearing'''

-you had me at puppy

-good intro (a few typos) and history (I like your table)

-the start of adult anatomy and histology should have an opening sentence instead of just listing information. There is no histology?

-I'm guessing the heading for development is meant to be bigger instead of it appearing to be part of "adult anatomy and histology"? This section is very comprehensive!

-your "neural domain" drawing is a good way of explaining this concept

-the summary box is a great idea, but perhaps it should be entitled "Summary of inner ear development"

-I don't understand why this is present- "NOTE: DEFINITIONS OF SYNDROMIC AND NON SYNDROMIC HEARING LOSS". You have explained what non-syndromic hearing loss is in the 1 Mutation of GJB2 gene section, but as your note says, it might be good to have a brief section with these definitions

-your genetic and structural disease tables are nice but I feel that the formatting should be the same for all of the diseases, or you should explain why you've chosen to emphasise these abnormalities

-the PDF in the Toxoplasmosis section seems to have some good info, but should be formatted like the other references

-the references in the rubella, cytomegalovirus infection, drugs and technologies to detect sections need to be formatted properly. Some info in drugs section isn't referenced at all

-technologies to detect is not a very informative heading, you need to specify what you're detecting. The syntax in this section and "technologies to overcome the problems" is poor (including the headings)

-in text hyperlinks in current research section are good for making page more interactive

-you appear to have used a lot of great resources

== References ==
<references/>

2012 Group Project 1

2012-10-03T00:05:58Z

Z3254758: /* Lacrimal Glands */

[[File:Eye_collage_2.jpg|right|830px]]

=Vision Development=

==Introduction==

Eyes are an important sensory organ shared across many different species and allow organisms to gather useful visual information from their environment. The visual system uses light from the environment and processes this information in the brain for visual perception. The visual system is complex, and is made up of various structures that work together to form vision. Each of the structures in the eye have specific tasks which contribute to the visual system. Knowledge of how the eye develops extends as far back as Aristotle more than 2000 years ago, and current knowledge shows that most of the crucial events of eye development occur in the embryological stage. The eye is an interesting model for studying the development of tissues in organisms, as it consists of cells from several parts of the embryo including the head ectoderm, neural ectoderm and mesoderm. From its many origins the cells come together and differentiate to produce the complex organ that is the eye. During this period there are many examples of inductive signaling, as the tissues coordinate their development throughout this elegant process.

The main anatomical structures of the eye are as follows:
{|
|
* Cornea

* Sclera

* Choroid

* Iris

* Ciliary body

* Lens

* Anterior chamber

* Posterior chamber

* Retina

* Optic nerve

|[[File:eye_diagram_bandw.jpg|right|250px|thumb|Basic structure of the human eye.]]
|}
[[File:Eyediagramcolour1.JPG|550px]]

==Research History==

=== '''Brief Timeline of Historical Developments on the Eye and its Embryology''' ===

{| width=800px
|-bgcolor="CEDFF2"
| width=100px|'''Time'''
| width=700px|'''Discovery'''

|-bgcolor="F5FAFF"
| '''Ancient Egyptians'''
| First to document cataracts. It is described as being 'the white disease of the eye' or 'darkening of the pupil.' <ref>Edwards, D.D. (1996). Ophthalmology before Hippocrates. In the History of Ophthalmology, ed. D.M. Albert and D.D. Edwards. Cambridge, Mass.: Blackwell Science.</ref> The Egyptians had some knowledge of the eye, however it is not known how much of the anatomy of the eye was known in their era.

|-bgcolor="CEDFF2"
| '''535 BC'''

|
Ancient Greek philosopher Alcmaeon conducted dissection of humans for the first time in recorded history. This included dissection of the eye. However, not much is known about which anatomical features he discovered. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17.">Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17.</ref>

|-bgcolor="F5FAFF"
| '''384- 322 BC'''

| [[File:Aristotle-eye.jpg|200px|thumbnail|The eye according to Aristotle.<ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "> Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau </ref> Note the lens is missing, and there are three vessels drawn that was believed to transport fluid to and from the eye.<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
]]
Aristotle performed dissections of animal embryos.<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

When Aristotle described the embryo of a ten day old chicken, he wrote "The eyes about this time, if taken out, are larger than beans and black; if their skin is removed the fluid inside is white and cold, shining brightly in the light, but nothing solid." <ref name="Magnus, H. (1998). Ophthalmology of the ancients. In J. Hirschberg (Ed.), The History of Ophthalmology: The monographs, Vol. 4, Part 1 (F.C. Blodi, Trans.) Bonn: Wayenborgh.">Magnus, H. (1998). Ophthalmology of the ancients. In J. Hirschberg (Ed.), The History of Ophthalmology: The monographs, Vol. 4, Part 1 (F.C. Blodi, Trans.) Bonn: Wayenborgh.</ref>

Aristotle believed that the eyes started forming during early embryogenesis, however, he also believed that the eyes are the last organs to form completely, and he incorrectly thought that the eyes shrink in later embryonic development. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press.">Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press.</ref> .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"

| '''340 BC'''

| Lens is thought to have been discovered by Hippocrates, due to his descriptions of the contents of the internal eye There has been studies in chick development later on by followers of Hippocrates. They claimed that eyes were visible in early embryogenesis. .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
|-bgcolor="F5FAFF"
|'''25 BC - 50 AD'''

| [[File:Celsus-eye.jpg|150px|thumb|The eye according to Celsus. <ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "/>
Note the lens is placed in the centre of the eye, in the vitreous.<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> ]]

Aulus Cornelius Celsus wrote a Roman medical text called 'De Medicina' in which he wrote that the lens was the part of the eye from which vision originated. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.">Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.</ref> Celsus also incorrectly drew the lens in the center of the globe in his diagram of the eye. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

|-bgcolor="CEDFF2"
| '''23-79 AD '''
|
Pliny the Elder said that the eye is the last of the organs to develop in the womb <ref name="Magnus, H. (1998). Ophthalmology of the ancients. In J. Hirschberg (Ed.), The History of Ophthalmology: The monographs, Vol. 4, Part 1 (F.C. Blodi, Trans.) Bonn: Wayenborgh."/>
|-bgcolor="F5FAFF"
| '''98-117 AD'''

| [[File:Rufus-eye.jpg|150px|thumb|The eye according to Rufus of Ephesus. <ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "/>
Note the lens is placed in the correct position, behind the iris of the eye <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> ]]

Rufus of Ephesus identified the lens as being located in the anterior part of the eye, close to the pupil. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

His diagram illustrates that he knew the correct position of the lens as being directly behind the iris, in the anterior part of the eye, and not in the centre as was previously depicted by others before him.

|-bgcolor="CEDFF2"
| '''130-200 AD'''

| [[File:Galen-eye1.jpg|150px|thumb|The eye according to Galen. <ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "/> ]]

Claudius Galen practised medicine in Rome. He wrote:

"1. Within the eye the principal orgran of sensation is the crystalline lens.

2. The sensation potential comes from the brain and is conducted via the optic nerves.

3. All other parts of the eyeball are supporting structures." <ref> Hirschberge, J. (1982). Antiquity, Vol. X in the History of Ophthalmology (F.C. Blodi, Trans.) Bonn: Wayenborgh. pp. 280 </ref>

Galen thought that the lens was produced from the vitreous. He also believed that the retina’s function was to give nourishment to the lens and vitreous, and to carry visual information to the brain from the lens. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

|-bgcolor="F5FAFF"

| '''1514-1564'''

| Andreas Vesalius published his anatomy book "De Humani Corporis Fabrica in 1543. He had the misconception that the lens was located in the centre of the eyeball. .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> He also wrote that the lens functioned "like a convex lens made of glass" <ref name="Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.">Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.</ref> pp. 48
|-bgcolor="CEDFF2"
| '''1535-1606'''

| Georg Bartisch correctly drew a diagram of the lens placed behind the iris in his book 'Ophthalmodouleia: das ist Augendienst'. <ref name="Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>
|-bgcolor="F5FAFF"

| '''1537-1619'''

| Fallopio Hieronymus Fabricius ab Aquapendente studied anatomy and embryology. He studied chicken embryos, and thought that chalazae (which comes from egg white) gives rise to the eyes. He also drew the lens directly behind the iris in a diagram in is book 'Tractatus de Oculo Visuque Organo. <ref name="Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

|-bgcolor="CEDFF2"
| '''1583'''

| Felix Platter published his book 'De corporis Humani Structura et Usu, after he performed dissections of human bodies. He believed that the retina is the primary visual organ in the eye. .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="F5FAFF"
| '''1619'''
| Scheiner is given credit to be the first person to correctly draw the diagram of the anatomy of the eye. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
|-bgcolor="CEDFF2"
| '''1672'''
| Marcello Malpighi described the embryonic development of the chicken. He drew many detailed diagrams of the chick eye. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1665'''
| Nicolaus Steno identified the choroid fissure in his study of a developing embryo of a chicken. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="CEDFF2"
| '''1754'''

| Albrecht von Haller studied the embryology of the eye. With help from his student Johann Gottfried Zinn, he contributed to the understanding of the development of the ciliary body, ciliary zonule, and their relationship with the lens and vitreous. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1817'''

| Christian Pander discovered the three embryonic germ layers, which he wrote about in his book. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/> Pander was the first to think of 'the optic vesicles as lateral evaginations' of the 'prosencephalon'; however, he was incorrect about the details regarding how 'the eye develops from these evaginations'. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="CEDFF2"
| '''1828-1837'''

| Karl Ernst von Baer studied embryology. He discovered that the optic vesicles were 'outgrowths of the embryonic forebrain' <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> which he believed was caused by pressure from fluids in the central nervous system. Von Baer also believed that the optic vesicle opens to form the pupil, and that fluid in the optic vesicle coagulates to form the vitreous body and lens. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1830'''

| Emil Huschke discovered that the lens forms from the invagination of the surface ectoderm. He concluded that the lens hence does not form ‘from the fluid of the optic vesicle’ <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> as previously thought.
|-bgcolor="CEDFF2"
| '''1832'''

| Emil Huschke wrote in his manuscript ‘Ueber die erste Entwinkenlung des Auges und die damit zusammenhängende Cyklopie’ that the lens capsule forms from the outer surface ectoderm, which detaches and moves back inward, which is later enclosed again by several membranes, such as by the cornea. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

Huschke also described how the optic cup and choroid fissure forms. He discovered that the optic vesicles are produced from the two-layered optic cup. However, he incorrectly described the destiny of the ‘individual optic cup layers’. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

|-bgcolor="F5FAFF"
| '''1838'''
| Matthias Jakob Schleiden and Theodor Schwann formulated the ‘cell theory’: “All living things are formed from cells, the cell is the smallest unit of life, and cells arise from pre-existing cells.” <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
|-bgcolor="CEDFF2"
| '''1839'''

| Theodor Schwann contributed a better understanding of the development of the lens through studying the foetus of a pig, which he wrote about in his book ‘Mikroskopische Untersuchungen Über Die Uebereinstimmung in Der Struktur Und Dem Wachsthum Der Thiere Und Pflanzen’. He wrote that the lens is made of ‘concentric layers’ of fibres which proceeds from an anterior to posterior direction. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1842'''
| Robert Remak gave the current names to the three embryonic germ layers: ectoderm, mesoderm and endoderm. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"
| '''1843'''
| Wilhelm Werneck published his book ‘Beiträge zur Gewebelehre des Kristallkörpers’. He wrote that the contents inside of the lens is not made of fluids, as was previously believed. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/> Werneck also discovered that the fibers of the lens continues to grow from the outside to the centre during embryogenesis. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

|-bgcolor="F5FAFF"
| '''1855'''

| Robert Remak wrote his book ‘Untersuchungen über die Entwickelung der Wirbelthiere’. He wrote about what he discovered in his studies of the development of the eye in the embryos of chickens, frogs, and rabbits. He wrote very descriptively about the embryology of lens formation, amongst other topics. He discovered that the ectoderm gives rise to the lens placode. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

|-bgcolor="CEDFF2"
| '''1858'''
| Henry Gray published his book 'Anatomy, Descriptive and Surgical'. He had also previously studied the embryonic development of the optic nerve and retina of chickens.
|-bgcolor="F5FAFF"
| '''1877'''
| Paul Leonhard Kessler wrote about the embryonic development of the lens in mice in his book ‘Zur Entwickelung des Auges der Wirbelthiere. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"
| '''1891'''
| Vincenzo Colucci studied newts and discovered their ability to regenerate the lens.<ref> Tsonis, P. A. (2001). Regeneration of the Vertebrate Lens and Other Eye Structures. eLS. (Online Publication). DOI: 10.1038/npg.els.0001102 </ref>
|-bgcolor="F5FAFF"
| '''1892'''
| Dr. Oscar Hertwig published his book ‘Text-Book of the Embryology of Man and Mammals. <ref> Hertwig, O. Text-book of the embryology of man and mammals. S. Sonnenschein 1901. (Translated from the 3d German ed. by Edward L. Mark.) </ref> It contains a very detailed description of the development of the eye, according to the findings at that time. [http://embryology.med.unsw.edu.au/embryology/index.php?title=Book_-_Text-Book_of_the_Embryology_of_Man_and_Mammals_16-2#The_Development_of_the_Eye]
|-bgcolor="CEDFF2"
| '''1895'''
| Gustav Wolff also independently studied newts and discovered their ability to regenerate the lens. .<ref> Tsonis, P. A. (2001). Regeneration of the Vertebrate Lens and Other Eye Structures. eLS. (Online Publication). DOI: 10.1038/npg.els.0001102 </ref>

|-bgcolor="F5FAFF"

| '''1900'''
| Carl Rabl published his book ‘Uber den Bau und die Entwicklung der Linse’. He wrote about the development of the lens in mammals, fish, birds, reptiles, and amphibians. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"
| '''1901'''
| Hans Spemann published his findings from his experimental studies about the formation of the lens in the frog. He found that the optic cup needed to be in contact with the ectoderm for normal development of the eye. <ref> Spemann, H. (1901). Über Correlationen in der Entwicklung des Auges. Verhand. Anat. Ges. 15: 61-79. </ref> <ref> Saha, M. (1991). Spemann seen through a lens. In Gilbert, S. F. (ed.). A Conceptual History of Modern Embryology. Plenum Press, NY. pp. 91-108.</ref>
|-bgcolor="F5FAFF"
| '''1906'''
| Brown ‘s book “The Embryology Anatomy and Histology of the Eye” was published. It contained detailed descriptions of the embryonic development of the eye according to the knowledge current at that time, mainly based on observations from embryos of rabbits and chickens. <ref> Brown, E.J. (1906). The Embryology Anatomy and Histology of the Eye. Chicago: Hazlitt & Walker. 1906 </ref>

|-bgcolor="CEDFF2"
| '''1907'''

| John Clement Heisler published his book ‘A Text-book of embryology’. It contains a chapter detailing the embryonic development of the eye, according to the knowledge current at that time. The book’s copyright has expired, so it can be viewed free online: [http://archive.org/details/atextbookembryo01heisgoog]

Julius Kollman also published his book 'Atlas of the Development of Man'. It contained very detailed description and illustrations showing the embryonic development of the human according to the knowledge current at that time. His illustrations were reused by many others after his time and built upon for further refined understanding of the embryology of the human.

Here are examples of Julius Kollman's excellent illustrations showing eye development in various stages:

'''Formation of Primary Optic Vesicle:'''
<gallery>
File:Kollmann691.jpg|The blue part at the bottom is the endoderm. The pink middle layer is the mesoderm. The top yellow layer is the ectoderm. The fold labelled as 'augenfeld' is the place where the optic vesicle will form.
File:Kollmann692.jpg|The eye area (augenfeld) is a bowl shaped bulge still located on the side walls.
File:Kollmann693.jpg| The neural tube is shown after removal of all of the ectoderm and ventral organs, such as heart, gut tube, etc. The primary optic vesicle forms a slightly flattened hollow protrusion on the forebrain.
File:Kollmann694.jpg|The lateral surface of the primary optic vesicle is slightly depressed, showing the first sign of the emergence of the secondary optic vesicle
</gallery>

'''Development of Lens:'''

<gallery>
File:Kollmann695.jpg|The bulging lateral wall of the primary optic vesicle is covered by a fairly well demarcated lens plate, a direct continuation of the ectoderm. Between the optic vesicle and the lens pit are some flattened spindle-shaped cells. In the adjoining mesoderm are cross-sections of capillaries.
File:Kollmann697.jpg|The lens still hangs together with the ectoderm. The primary eye vesicle is indented with respect to the lens. Between the lens and the lateral plate of the optic vesicle is a narrow space, which allows area to further develop later.
File:Kollmann698.jpg|4th Week of development. The internal organisation shows the secondary optic vesicle. A: The rear wall of lens is noticeable and is enveloped by mesoderm. B: The edges of the lens pit is already grown and the lens vesicles are formed, which is still related to the remaining ectoderm.
File:Kollmann699.jpg|The lens has now cut off from the ectoderm, but is still very superficial. Between it and the lateral lamina of the optic cup, there is a considerable space. The eye stalk has become longer and is enclosed together with the optic cup and lens of the mesoderm. The cornea, sclera and choroid make gradual development.
</gallery>

|-bgcolor="F5FAFF"

| '''1921'''
| Bailey and Miller published their textbook “Text-Book of Embryology “. <ref> Bailey, F.R. and Miller, A.M. (1921). Text-Book of Embryology. New York: William Wood and Co. (Note- This book is only at an early edited stage)</ref> It contains detailed description of the development of the embryonic eye according to the knowledge current at that time. [http://embryology.med.unsw.edu.au/embryology/index.php?title=Book_-_Text-Book_of_Embryology_18]

|-bgcolor="CEDFF2"
| '''1925'''

| Mann published his research article, in which he gives a detailed account of the development of the human iris. He divided the development of the iris into four stages: weeks 4-7 (before the ectodermal iris forms or before the anterior chamber forms); weeks 7-11 (anterior chamber appears, and mesodermal iris forms); weeks 11-12 (ectodermal iris forms); 3-8 months (muscles of the pupil forms from ectodermal iris, and the central portion of the mesodermal iris atrophies to make the pupil clear). <ref name="PMID18168466"><pubmed>18168466</pubmed></ref>
O Leser also published an article detailing the development of extraocular muscles in mammals he studied. <ref name="PMID18168498"><pubmed>18168498</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1939'''
| Holtfreter <ref> Holtfreter, J. (1939). Gewebeaffinitat, ein Mittel der embryonalen
Formbildung. Arch. Exp. Zellforsch. 23, 169-209. </ref> studied amphibians and observed that that the development of the eye stops at the ‘optic vesicle stage’ if there is no contact ‘with the epidermis and neural crest driven mesenchyme’. <ref name=”PMID11023863”><pubmed>11023863</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1955'''
| Barber published his book ‘Embryology of the human eye’. <ref> Barber AN: Embryology of the human eye. St. Louis. CV Mosby 1955</ref> In contains detailed descriptions of the embryological development of the human eye according to the knowledge current at that time. It contains many photographs of the eye at different stages of development.

|-bgcolor="F5FAFF"
| '''1957'''
| Coulombre studied a chicken embryo to find the role of intraocular pressure in the development of the chick’s eye, especially in regards to its control of the size of the eye structures. <ref name="PMID13469954"><pubmed>13469954</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1958'''
| Coulombre studied the development of the cornea and how it develops its transparency. <ref name="PMID13563560"><pubmed>13563560</pubmed></ref> He also studied the development of corneal curvature. <ref name="PMID 13519969"><pubmed> 13519969</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1962'''
| Coulombre studied the development of the conjunctival papillae and scleral ossicles. <ref name="PMID 14023393"><pubmed> 14023393</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1963'''
| Coulombre studied the development of lens fibers and their orientation. <ref name="PMID14077035"><pubmed>14077035</pubmed></ref> He also studied the development of pigmented epithelium. <ref name="PMID14023394"><pubmed>14023394</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1964'''

| Coulombre further studied the development of the lens to determine the role of the lens in eye growth. <ref name="PMID14189921"><pubmed>14189921</pubmed></ref> He also studied the role of thyroid in the development of the cornea and the development of corneal transparency. <ref name="PMID14211912"><pubmed>14211912</pubmed></ref> Mann also published his work called ‘The development of the human eye’, which contains detailed description of the embryonic development of the eye according to current knowledge at that time. <ref> Mann I. The development of the human eye. New York: Grune and Stratton 1964</ref>

|-bgcolor="CEDFF2"
| '''1965'''
| Coulombre published his findings regarding the regeneration of the neural retina from pigmented epithelium in the embryo of chickens. <ref name="PMID5833111"><pubmed>5833111</pubmed></ref> Smelser also published his findings on the embryological development and morphology of the lens. <ref name="PMID14340157"><pubmed>14340157</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1966'''

| Formation of the face and orbit occurs from the differentiation of neural crest cells. <ref name="PMID5969670"><pubmed>5969670</pubmed></ref> O’Rahilly also published findings of the development of the eye in the early stages of human embryos. <ref> O'Rahilly, R. 1966 The early development of the eye in staged human embryos. Contr. Embry. Carnegie Inst., Wash., 38: 1–42</ref>

|-bgcolor="CEDFF2"
| '''1968'''
| Findings of the postnatal development of the retina of rats was published. <ref name="PMID5640327"><pubmed>5640327</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1969'''

| Mann again published his work called ‘The development of the human eye’. He stated that that the lens in humans forms completely from the ectoderm. <ref name=”Mann I. The Development of the Human Eye. New York, USA: Grune & Stratton, Inc; 1969”> Mann I. The Development of the Human Eye. New York, USA: Grune & Stratton, Inc; 1969</ref> Coulombre also studied the development of the lens, and took note of its size, shape and orientation throughout its developmental stages. <ref name="PMID 5772716"><pubmed> 5772716</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1970'''
| Coulombre again further studied the regeneration of the neural retina from pigmented epithelium of embryos of chickens. <ref name="PMID 5472476"><pubmed> 5472476</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1971'''

| Coulombre further studied the development of the lens. This time he focused on analysing the histological mechanisms in the reconstitution of the lens from implanted lens epithelium. <ref name="PMID 4925671"><pubmed> 4925671</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1973'''
| A research article was published, detailing the embryonic development of the retina of humans. <ref name="PMID 6650859"><pubmed> 6650859</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1976'''

| Geeraets published his observations of the closure of the embryonic optic fissure in golden hamsters, using the electron microscope. <ref name="PMID 1266776"><pubmed> 1266776</pubmed></ref> Kornneef also published an article based on his studies of the development of connective tissue in the human orbit. <ref name="PMID 1020699"><pubmed> 1020699</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1981'''
| A research article was published detailing how myelin forms in the optic nerve of humans. <ref name="PMID 7224936"><pubmed> 7224936</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1983'''
| O’Rahilly’s further research developments was published, reporting the timing and sequence of events in the development of the embryonic human eye. <ref name="PMID 6650859"><pubmed> 6650859</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1990'''

| Van Driell et al. <ref>Driell, D. Van; Provis, J.M.; Billson, F.A.: Early differentiation of ganglion, amacrine, bipolar and Muller cells in the developing fovea of the human retina. J. Comp. Neurol. 291: 203-219.</ref> studied the manner in which amacrine, bipolar, retinal ganglion cells, and Muller cells differentiate in the developing fovea of the retina of a 15-week old human foetus. <ref name="PMID1628748"><pubmed>1628748</pubmed></ref> Tripathy also published an article providing evidence that the lacrimal glands in humans originates from the neuroectoderm. <ref name="PMID2406219"><pubmed>2406219</pubmed></ref>

|}

==Development, Structure and Function of Ocular Components==

The eye itself is formed from several components; notably the optic placode of the head ectoderm, the optic vesicle from the neural tube, and mesenchyme from the mesoderm and neural crest cells. The optic placode contributes the lens to the eye, the optic vesicle gives rise to layers of the retina, while the mesenchyme will produce the ciliary body, iris, choroid and sclera.<ref>http://www.vetmed.vt.edu/education/curriculum/vm8054/eye/EMBYEYE.HTM</ref> Cells from the neural tube will also produce the optic nerve, which receives nerve impulses from the retina of the eye. Eyes initially form as laterally paired structures and migrate medially in the human embryo. In other animals such as birds and lizards, the eyes do not migrate and develop laterally on the head. The optic placodes become prominent on the surface of the embryo at approximately Stage 14 of development.

[[File:Stage14 sem2b-limb.jpg|200px|thumb|left|A Stage 14 embryo showing the location of an otic placode.<ref name="http://embryology.med.unsw.edu.au/embryology/index.php?title=ANAT2341_Lab_6_-_Early_Embryo">http://embryology.med.unsw.edu.au/embryology/index.php?title=ANAT2341_Lab_6_-_Early_Embryo</ref>]] [[File:Stage 13 image 060.jpg|400px|thumb|center|A cross section showing the organisation of the developing brain, the optic vesicle and the lens (optic) placode.<ref name="http://embryology.med.unsw.edu.au/embryology/index.php?title=ANAT2341_Lab_6_-_Early_Embryo"/>]]

===Optic Nerve===

The optic nerve consists of nerve fibres that transmit information from the retinal photoreceptor cells to the brain. The optic nerve is formed from the optic stalk, which develops as the optic vesicle migrates from its origin in the neural tube to its destination - the surface ectoderm - where it will fuse with the optic placode (also known as the lens placode, which will contribute the lens to the eye).<ref name="PMID11687490"><pubmed>11687490</pubmed></ref>

[[File:Formation of the optic vesicle 1.jpg|400px|thumb|left|Fig. 1: Early formation of the optic vesicle from the neural groove.]] [[File:Formation of the optic vesicle 2.jpg|400px|thumb|center|Fig. 2: The optic vesicle at a later stage, showing the optic stalk.]]

As can be seen in Figure 1 above, the optic vesicle forms from the neural tube. However, note that the neural tube has not yet closed, and is still the neural groove at this point. Figure 2 then shows the optic vesicle at slightly later stage in the same simplified cross-section of the embryo, as it migrates from the neural tube to the surface ectoderm. Note the presence of the optic stalk which links the optic vesicle to the neural tube. Later in development, this primitive structure will become the optic nerve, which will link the eye to the brain.

The nerve fibres themselves will initially originate from the retinal ganglion cells in the eye during week 6.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008">Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008</ref> After two weeks, these fibers will have grown along the inner wall of the optic stalk and have reached the brain. They grow both in length and width, with the nerve fibres filling the hollow optic stalk to form the solid optic nerve. More than one million nerve fibers will eventually make up the optic nerve, along with glial cells which arise from the inner wall of the optic stalk itself.<ref><pubmed>1451666</pubmed></ref> Myelinisation of the optic nerve begins much later in development at around 7 months, beginning at the optic chiasm and moving towards the eye.<ref><pubmed>7224936</pubmed></ref> The optic chiasm forms just before the nerves reach the brain, and is where half the nerve fibres from each eye will cross over to the opposite side of the brain. This is demonstrated in Figure 3. Note the crossing over of the optic nerves just before they enter the brain, at the optic chiasm. This organisation is now much more familiar, with the eyes near the ectoderm and the optic nerve leading through the mesoderm to the brain buried deep in the embryo.

[[File:Formation of the optic nerve and chiasm 1.jpg|400px|thumb|center|Fig. 3: A recognisable brain and eye structure in later development.]]

===Retina===

The retinal component of the eye is formed when the optic vesicle folds in upon itself, forming the optic cup (see Figure 4). In doing so it creates two layers - an inner wall and an outer wall of the optic cup (Figure 5). These two layers of the optic cup will give rise to the two layers of the retina - the inner neural retina, and the outer pigmented epithelium.<ref name="PMID11687490"/> Note the existence of the space between the two layers of the retina. This is known as the intraretinal space and disappears by the 7th week of development, however the two layers never completely fuse and can become separated as a result of physical trauma to the head - leading to a detached retina and loss of vision.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/>

The inner wall of the optic cup, which will give rise to the neural retina, consists of a layer of pseudostratified cells (see Figure 6) that later differentiate into rod, cone, bipolar, ganglion, horizontal, amacrine and glial cells of the retina (Figure 7).<ref name="PMID18168748"><pubmed>18168748</pubmed></ref> The outer wall of the optic cup consists of a layer of cuboidal cells that contain melanin - the light absorbing pigment. The function of this layer is to absorb light and prevent internal reflection of light within the eye, which would impair our ability to form distinct images. Interestingly, in some animals such as cats, this layer actually reflects light intentionally to increase the amount of light available to the eye in low-light conditions. This is why cats seem to have eyes that glow in the dark.<ref>http://dialspace.dial.pipex.com/agarman/bco/fact4.htm</ref>

[[File:Formation of the optic cup 1.jpg|400px|thumb|left|Fig. 4: Mechanism of optic cup formation.]] [[File:Formation of the optic cup 2.jpg|400px|thumb|center|Fig. 5: Layers of the optic cup in retina development.]]

The inner wall itself is divided into two components - the inner neuroblastic layer and the outer neuroblastic layer (see Figure 6). The outer neuroblastic layer forms the rod and cone cells while the inner neuroblastic layer forms the remaining cell types found in the retina - the bipolar, ganglion, horizontal, amacrine and glial cells (Figure 7).<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/> The organisation of the retina is interesting in that incoming light passes through several layers of these neural retina cells before it is detected by rod and cone cells at the back of the retina, and then nerve signals are passed back through the layers of neural retina cells that the light just passed through moments before - a seemingly strange design that the eye does not share with man-made light-capturing devices such as a camera (imagine putting the wires in front of the image sensor!).

Differentiation of the neuroblastic layers into neural retina cells occurs in a pattern both within the layers and across the retina. Cells differentiate from the inner neuroblastic layer to the outer neuroblastic layer, and differentiate from the central retina to the peripheral retina.<ref name="PMID18168748"/> The macula is first identifiable in week 22 when ganglion cells start to form multiple rows, and the primitive fovea begins to form at approximately the same time as a depression in the macula.<ref><pubmed>6462623</pubmed></ref> It is not until 15-45 months after birth that this area becomes exclusively populated by cone cells and becomes the fovea centralis - the area of the retina with the highest visual acuity.

[[File:Formation of the retina 1.jpg|400px|thumb|left|Fig. 6: Cross-section of the primitive retina showing cell types and layers.]] [[File:Formation of the retina 2.jpg|400px|thumb|center|Fig. 7:Cross-section of a developed retina showing cell types and layers.]]

===Ciliary Body===

The ciliary body consists of ciliary processes and three portions of fibres that constitute the ciliary muscles. It functions to maintain normal eye physiology as well as playing a direct role in accommodation.

During development, the ciliary processes form slightly posterior to the iris, developing from part of the anterior rim of the optic cup. It is thought that the folded structure of the ciliary processes is brought about by intraocular pressure and specific signalling pathways.<ref name="PMID16959249"><pubmed>16959249</pubmed></ref> While the ciliary muscles and the endothelial cells of the ciliary blood vessels are chiefly formed by mesenchymal cells<ref><pubmed>16249499</pubmed></ref>, the neural crest and neuroectoderm also contribute to their development.<ref><pubmed>12127103</pubmed></ref> The normal development of the ciliary body is dependent on the correct expression of bone morphogenetic protein (BMP)-4, which is a member of the transforming growth factor-β superfamily.<ref><pubmed>1222340</pubmed></ref> Napier and Kidson (2007) summarised numerous genes that have been associated with ciliary body development, however their direct roles have not been well documented.<ref name="PMID16959249"/>

===Iris===

The iris is a thin layer that develops at the end of the third month of development and is derived from the anterior rim of the optic cup. The stroma of the iris develops from cells of neural crest cell origin.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/> The muscles that are responsible for the dilation and constriction of the pupil (dilator pupillae and sphincter pupillae muscles) form from the neuroectoderm of the optic cup. These cells are initially epithelial cells that then transform into smooth muscle cells. <ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"></ref>. The invagination of the optic vesicle which creates the optic cup, also causes the formation of the optic cup lip. This is the region of the where the epithelium doubles back, separating the outer pigmented layer and the inner nonpigmented layer. This is the edge of the iris that borders on the pupil<ref><pubmed> Retinal and anterior eye compartments derive from a common progenitor pool in the avian optic cup</pubmed></ref>.

The final colour of the iris is not evident until the postnatal period. It is determined by a number of genes including IRF4, SLC24A4 and MATP<ref><pubmed>19710684</pubmed></ref>. Other features such as crypt frequency, furrow contractions, presence of peripupillary pigmented ring, and number of nevi also become evident during development<ref><pubmed>21835309</pubmed></ref>. Mutations in Pax6 have been shown to cause partial or complete loss of the iris <ref><pubmed>12386935</pubmed></ref>.

===Cornea===

The cornea is the transparent, avascular, most anterior portion of the eye. It is responsible for conducting light into the eye and focusing it on to the retina, as well as maintaining the rigidity of the eyeball. It consists of 5 layers- the epithelium, Bowman’s layer, stroma, Descemet’s membrane and the endothelium.

The epithelium and endothelium of the cornea first appear during the 5th week of gestation. The epithelium of the external surface of the cornea is derived from surface ectoderm, while the mesenchyme is derived from the mesoderm<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"/>. The endothelium is a two-cell cuboidal layer which is made up of differentiated neural crest cells that were initially from the optic cup. By week 8 the endothelial cells begin to secrete a basement membrance which later forms Descemet’s membrane<ref><pubmed>6511224</pubmed></ref>. At approximately 16 weeks gestation the Bowman’s membrane begins to form from the thickening of the stroma that is located under the corneal epithelium<ref>Riordan-Eva P, Whitcher JP. Vaughn and Asbury's General Ophthalmology, Lange Medical Books/McGraw Hill. 2004:25–27</ref>. During the third month glycosaminoglycans secreted by fibroblasts form the ground substance of the cornea, with collagen fibrils and keratan sulphate also appearing around this time. Shortly after this tight junctions form between the endothelial cells<ref><pubmed>19481138</pubmed></ref>. Fibroblast growth factor causes the epithelial cells to proliferate<ref><pubmed>20105280</pubmed></ref>.

Towards the end of the gestational period the cornea becomes larger due to the production of aqueous humor<ref>Yanoff M, Duker JS. Ophthalmology. Mosby; St. Louis, MO: 2004</ref>. The final transparent structure develops because hyaluronidase removes hyaluronic acid, thyroxine causes dehydration of the stroma, and the entire structure becomes avascular<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/>. Numerous genes have been implicated in the development of the cornea, these include, but are not limited to, PAX6, PITX2, FOXC1, MAF, TMEM114, SOX2, OTX2 and BMP4<ref><pubmed>18637741</pubmed></ref>. Pax6 and Pax6(5a) isoforms are essential for the normal development of the eye. Over or under expression can both lead to major structural abnormalities<ref><pubmed>18386822</pubmed></ref>.

===Lens===

The lens has its origin from the optic placode, which develops on the ectodermic surface of the embryo and migrates both medially and inwards into the embryo. The lens allows accommodation of the eye, and adjusts its thickness in order to focus on near or far objects. The study of lens development was one of the first to highlight the importance of inductive signaling in development, with Spemann's pioneering work at the start of the 20th century, finding that the absence of retinal development resulted in the absence of lens formation.<ref name="PMID11687490"/> Indeed, it has been consistently shown that the interaction of the migrating optic vesicle with the surface ectoderm of the head is vital in producing differentiation of the lens.<ref name="PMID15558475"><pubmed>15558475</pubmed></ref> The mechanism of interaction is complex but basically involves upstream genes switching on downstream genes, with the genes eventually producing specialised proteins which constitute the lens. The whole process starts with the signaling molecules from the optic cup initiating a thickening of the surface ectoderm of the head (Figure 8). It is thought that this region of specific ectoderm is responsive to the signaling molecules, as lens formation is incomplete or absent when ectoderm from the lateral portion of the embryo (i.e. non-head ectoderm) is exposed to the same inductive signaling processes.<ref name="PMID9216064"><pubmed>9216064</pubmed></ref> Pax6 has been shown to be one of the major genes required for differentiation of the lens, which in turn switches on transcriptional genes such as Sox 1, 2 and 3 among others - producing water-soluble proteins called crystallins - responsible for giving the lens its transparency and refractive properties.<ref name="PMID9609835"><pubmed>9609835</pubmed></ref>

[[File:Formation of the lens 1.jpg|400px|thumb|left|Fig. 8: The importance of the optic cup in lens differentiation.]] [[File:Formation of the lens 2.jpg|400px|thumb|center|Fig. 9: The lens placode separates from the ectoderm and migrates into the mesoderm forming the lens vesicle.]]

The lens placode invaginates from the head ectoderm and migrates into the mesoderm (Figure 9). Once this structure (now known as the lens vesicle) is in place opposite the optic cup, the combined structure is referred to as the optic globe and resembles a recognisable eye structure. The lens continues to differentiate further, as mentioned above, through the formation of crystallin proteins, which give the lens its unique properties and allows for the fine control over the degree of refraction that takes place.

===Aqueous Chambers===

There are both anterior and posterior aqueous chambers of the eye which contain aqueous humour. A space develops in the mesenchyme situated between the lens and cornea to form the anterior aqueous chamber. The mesenchyme located superficially to this chamber forms the mesothelium as well as the transparent portion of the cornea.

The posterior chamber develops from a similar space in the mesenchyme, however it is located between the iris and the lens. The anterior and posterior chambers are able to communicate with one another once the papillary membrane vanishes and the pupil is formed. This channel is known as the scleral venous sinus.<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011">Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011</ref>

Contained within the aqueous chambers is aqueous humor. The production of aqueous humor is dependant on the development of the ciliary body. It is produced in the ciliary processes and it’s production is a metabolic process driven by the delivery of oxygen and the removal of wastes via the ciliary circulation<ref><pubmed>20801226</pubmed></ref>.

===Choroid and Sclera===

The choroid and sclera are adjacent layers that surround the eye and act to vascularise and protect the eye respectively. They are formed from neural crest and mesoderm-derived mesenchyme which condenses around the optic cup and lens vesicle between weeks 5 and 7 of development to form a primitive eyeball structure known as the optic globe.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/> Blood vessels first start to appear in the choroid layer at approximately week 15, and arteries and veins can be distinguished by week 23.<ref>Development of the Choroid and Related Structures, K. Sellheyer, Eye (1990) 4, 255-261</ref> Inductive processes are thought to play a vital role during formation of the choroid and sclera; with the retinal pigmented epithelium inducing differentiation of the surrounding mesenchyme while at the same time the neural crest-derived mesenchyme contributing components to the retinal pigmented epithelium such as melanocytes.<ref name="PMID1628748"/> In addition to having functional roles themselves, the primitive choroid and sclera also contribute components to the developing ciliary body and cornea (Figure 10). In the adult eye, the choroid is continuous with the ciliary body and the sclera with the cornea.

[[File:Formation of the choroid and sclera 1.jpg|400px|thumb|center|Fig. 10: The choroid and sclera derives from mesenchyme surrounding the optic cup.]]

===Eyelids===

The eyelids are ectodermal and mesodermal in origin and are an extension of the skin which covers and protects the eye. The surface ectoderm gives rise to the conjunctiva, skin epithelium, hair follicles, cilia, Zeis glands, glands of Moll, and meibomian glands. <ref name=" Cook CS, Ozanics V, Jakobiec FA. (1994) Prenatal development of the eye and its adnexa. In Tasman W, Jaeger EA, editors: Duane’s foundations of clinical ophthalmology, vol 1, Philadelphia, 1994, Lippincott. "> Cook CS, Ozanics V, Jakobiec FA. (1994) Prenatal development of the eye and its adnexa. In Tasman W, Jaeger EA, editors: Duane’s foundations of clinical ophthalmology, vol 1, Philadelphia, 1994, Lippincott. </ref> The mesenchyme gives rise to the tarsal plates, levator muscles, orbicularis muscles, and tarsal muscle of Muller. <ref name=" Cook CS, Ozanics V, Jakobiec FA. (1994) Prenatal development of the eye and its adnexa. In Tasman W, Jaeger EA, editors: Duane’s foundations of clinical ophthalmology, vol 1, Philadelphia, 1994, Lippincott. "/> Eyelid formation can be first noted during week 5 when small grooves develop in the surface ectoderm (Figure 11).<ref><pubmed>7364662</pubmed></ref> These small grooves deepen and extend into the mesoderm and the primitive eyelid structures grow towards one another, eventually fusing together during week 8.<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"/> It is not until week 26-28 that the eyelids will separate again. The anterior surface of the eyelid becomes covered by two layers of epithelium; this forms the epidermis of the eyelids. <ref name="Kikkawa DO, Lucarelli MJ, Shovlin JP, et al: Ophthalmic facial anatomy and physiology. In Kaufman PL, Alm A, editors: Adler’s physiology of the eye, St Louis, 2003, Mosby, pp 16."> Kikkawa DO, Lucarelli MJ, Shovlin JP, et al: Ophthalmic facial anatomy and physiology. In Kaufman PL, Alm A, editors: Adler’s physiology of the eye, St Louis, 2003, Mosby, pp 16.</ref> Tarsal plates then begin to develop, which eventually leads to the formation of meibomian glands. <ref name="PMID1628748"/> The ectoderm reflects over the developing cornea to form the conjunctival sac, a space that is filled by secretions from the lacrimal gland in order to allow smooth motions of the eyelid over the eye and also to clean the cornea and prevent accumulation of particles on the eye that may disrupt vision. By the time the eyelids separate, the eye has all its major components present (Figure 12), and further development consists mainly of growth and vascularisation.

[[File:Formation of the eyelid 1.jpg|400px|thumb|left|Fig.11: Small grooves in the ectoderm of the head - the precursors to an eyelid.]] [[File:Formation of the eyelid 2.jpg|400px|thumb|center|Fig. 12: The eye at an advanced stage of embryonic development. Note however, that the eyelids remain fused until much later.]]

===Lacrimal Glands===

There are three stages of lacrimal gland development. The first is the presumptive glandular stage in which the superior conjunctival fornix epithelium thickens and the surrounding mesenchymal cells condense. These mesenchymal cells are of neural crest origin<ref><pubmed>9882499</pubmed></ref>. The second stage sees the development of nodular formations around the superior conjunctival fornix and the formation of lumina within the epithelial buds, this stage is therefore known as the bud stage. Innervation and vascularisation also occur during this stage. The final morphological changes occur during the glandular maturity stage which occurs in weeks 9-16 when the lacrimal glands begin to resemble the mature glands. During the 13th week the lacrimal and zygomatic nerves anastomose<ref><pubmed>14635806</pubmed></ref>.

These glands are responsible for the production of tears however they do not start to function until 1-3 months after birth. The mature lacrimal gland is made up of two lobes- the palpebral and orbital lobes.

==Current Research==

===The impact of visible light on the immature retina===

<pubmed>22405869</pubmed>

The authors mentioned in this article <ref name="PMID22405869"><pubmed>22405869</pubmed></ref> that they were interested in investigating the effect of light on postnatal eye development in mice, because mice are born with fused eyelids, which separate 12 days after birth. Before the eyelids separate, the retina develops in mice with very little radiation from light. It is believed that the darkness plays a role in the development of the retina in mice, which is why their eyelids are fused for 12 days after birth. Therefore the authors were interested to see what effect light would have on postnatal retinal development of mice, with special interest in retinal ganglion cells (RGC). In their experiment, they surgically opened the eyelids on the right eyes of some of the mice to expose them to visible light 12 hours per day, while they left some other mice in the dark after surgical separation of their eyelids. They also kept the left eyes of the mice naturally fused as controls in the experiment. Their results showed that early light exposure in mice causes a decrease in retinal ganglion cells because it affects cellular apoptosis in the retina. The authors also observed that early exposure to light in mice causes lumican mRna transcription to resume and to quickly increase. (Lumican normally stays silent in retina after birth).

---------

===GABA Maintains the Proliferation of Progenitors and Non-Pigmented Ciliary Epithelium===

<pubmed>22590629</pubmed>

{| width=800px
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| width=450px|
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|-
| GABA is an ‘inhibitory neurotransmitter’ in the central nervous system of adults. <ref name="PMID22590629"><pubmed>22590629</pubmed></ref> It is responsible for controlling proliferation of stem cells and progenitor cells. The authors of this article <ref name="PMID22590629"/> was interested to find the effects of GABA on proliferation of progenitor cells and non-pigmented ciliary epithelial cells (NPE) in the retina. Their study focused on progenitor cells and non-pigmented epithelium of the ciliary body in chickens. Non-pigmented epithelial cells in chickens arise from the neuroepithelium of the optic cup. They share similar functions as progenitors of the early retina, such as expression of Chx10 and Pax6 genes. It is not agreed upon whether epithelial cells of the ciliary body have stem cell properties. However, it has been found that these cells can be cultured and transplanted into retinas that are injured, in order to replace neurons that were previously lost. However, there is not much known about what factors regulate the proliferation of stem cells. Hence the authors were interested in finding the effects of GABA on proliferation of retinal cells. Their results showed that non-pigmented epithelial cells in chickens ‘express extrasynaptic-like GABAA receptors’ that have the ability to regulate cell proliferation. It has been found that inhibiting these ‘GABAA receptors’ also causes a decrease in proliferation of retinal progenitor cells and non-pigmented epithelial cells in 'the intact E8 retina’. <ref name="PMID22590629"/>

|
[[File:Gaba-effects-retina.JPG|thumbnail|250px|'''GABAA receptor mediated effects on retinal progenitor cell proliferation'''
]]
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===Stem Cells===

[http://www.advancedcell.com/patients/clinical-trial-information/ Advanced Cell Technology]- A biotechnology company which is currently running two clinical trials that utilise human embryonic stem cell derived retinal pigmented epithelial cells. These trials are examining the possibility of using these cells to treat stargardt's macular dystrophy and dry age-related macular degeneration<ref><pubmed>22281388</pubmed></ref>.

-------------------

===MIP/Aquaporin 0 Represents a Direct Transcriptional Target of PITX3 in the Developing Lens===

<pubmed>21698120</pubmed>

{| width=800px
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|PITX3 plays a siginificant role in the development of lens in vertebrates. If there is a deficiency is PITX3, it causes a range of problems in humans such as microphthalmia, Peter’s anomaly, or isolated cataracts. Mutation of PITX3 also causes degeneration of the lens in zebrafish and mice. It is therefore important to understand what factors may affect the decrease in PITX3, as a normal level of PITX3 is needed to maintain normal eye development. The authors wanted to investigate specific genes which are affected by PITX3. Previous research has shown that MIP and Aquaporin causes defects in the lens in both mice and humans. MIP and Aquaporin are targeted by PITX3, so their imbalance is interrelated in the cause of defects in the lens. Therefore it has been previously proven that PITX3 is needed for normal development of the lens. However, there has not been much information previously known regarding the exact effect that PITX3 has, or the specific genes it targets. Since MIP and Aquaporin is common genes found in humans, mice and zebrafish, the authors <ref name="PMID21698120"><pubmed>21698120</pubmed></ref> chose to study these genes to understand the pathway that PITX3 takes and its exact involvement in the development of the lens. Their results proved that deficiency in MIP and Aquaporin indeed affects normal development of the lens, and it is indeed related to deficiency in PITX3. However, there is still more research needed to understand PITX3 and the genes it interacts with, and their effect in ocular development.

|
[[File:Mip1-expression-in-pitx3.jpg|thumbnail|250px|'''Analysis of mip1 expression in pitx3-mo and control embryos via in situ hybridization and RT-PCR''']]
|}

-------------------

===Activation of c-Jun N-terminal kinase (JNK) during mitosis in retinal progenitor cells.===

<pubmed>22496813</pubmed>

{| width=800px
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| In the past, most studies about c-Jun N-terminal kinase (JNK) in the retina have been in relation to neurodegeneration. <ref name="PMID22496813"><pubmed>22496813</pubmed></ref> Therefore the authors in this article were interested in investigating the function of c-Jun N-terminal kinase in the retinal progenitor cells in neonatal rats. <ref name="PMID22496813"/> In the experiment, they took retinal tissue from newborn rats and fixed them, and subsequently examined them using confocal microscopy and fluorescence to discover c-Jun N-terminal kinase ‘phosphorylation by immunohistochemistry’. <ref name="PMID22496813"/> Mitotic cells in the retina were identified during the experiment. The results of their experiment revealed that c-Jun N-terminal kinase is phosphorylated in the developing retina of neonatal rats during the mitosis of progenitor cells. <ref name="PMID22496813"/> This shows that c-Jun N-terminal kinase can control the proliferation of progenitor cells in the developing retina. Their experiment also revealed that inhibiting c-Jun N-terminal kinase causes disruptions to the mitotic cell cycle by reducing the cell numbers in anaphase. <ref name="PMID22496813"/> However, inhibiting c-Jun N-terminal kinase did not change the cell numbers in metaphase or prophase. <ref name="PMID22496813"/>

|
[[File:JNK1.png|thumbnail|300px|'''"JNK is phosphorylated during mitosis of retinal progenitor cells."''']]
|}

----------------------------

===LRP5 is required for vascular development in deeper layers of the retina===

<pubmed>20652025</pubmed>

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|-
|
The lipoprotein receptor-related protein 5 (LRP5) has a significant function in the development of retinal vasculature.<ref name="PMID20652025"><pubmed>20652025</pubmed></ref> Research has shown that mutations of the LRP5 causes loss of function, due to incomplete development of retinal vessel network, in both humans and mice. The authors investigated how mutations occur in the LRP5, which leads to abnormal development of the retinal vasculature. They have studied retinal endothelial cells in mutant mice in their study. Their results showed that in retina with mutated LRP5, endothelial cells in the retinal vasculature primarily produced cell clusters in the inner-plexiform layer instead of migrating into deeper layers of the retina to form normal retinal vasculature. The authors also discovered that there was a decrease in Slc38a5, which is “a Müller cell-specific glutamine transporter”, in mice with mutated LRP5. Their results lead the authors to conclude that normal LRP5 is very important in the development of normal retinal vasculature due to their role in causing migration of retinal endothelial cells in the deeper layers of the retina. LRP5 is also important for retinal interneurons and Müller cells to function correctly.

|
[[File:Retina-cell-clusters.JPG|350px|thumbnail|'''Endothelial cells form thick clusters in the LRP5 mutant retina''']]
|}

-----------------

===Astrocyte-Derived Vascular Endothelial Growth Factor===

<pubmed>20686684</pubmed>

{| width=800px
|-
|
Vascular endothelial growth factor (VEGF) has an important role in normal development of retinal vasculature. <ref name="PMID20686684"><pubmed>20686684</pubmed></ref> In the process of vascularisation of the retina, the retinal astrocytes (both vascularised and not yet vascularised) expresses the vascular endothelial growth factor. <ref name="PMID20686684"/> This fact indicates that vascular endothelial growth factor that are derived from astrocytes of the retina plays an important role in vessel maturation and angiogenesis. <ref name="PMID20686684"/> Therefore the authors wanted to test the role of vascular endothelial growth factor that are derived from astrocytes to find further confirmation. ‘Cre-lox technology’ was used in the experiment to remove the vascular endothelial growth factor from mice retinal astrocytes in the developmental period. <ref name="PMID20686684"/> The results showed that removing vascular endothelial growth factor that are derived from astrocytes caused ‘the regression of smooth muscle cell-coated radial arteries and veins’ from the effects of hyperoxia. <ref name="PMID20686684"/> Hence, this result indicates that vascular endothelial growth factor plays an important role in stabilising blood vessels during the development of the retinal vasculature. <ref name="PMID20686684"/> It has been suggested that this finding may be of relevance to retinopathy in premature neonatal humans. <ref name="PMID20686684"/>

[[File:Astrocyte-vegf-deletion.JPG|250px|thumbnail|'''"Astrocyte specific deletion of VEGF." ''']]
|
[[File:Effect-of-vegf-on-retinal-vasculature.JPG|250px|thumbnail|'''"Effects of astrocyte-derived VEGF on retinal vascular development."''']]
[[File:Vegf-protects-vessels.JPG|250px|thumbnail|'''Astrocyte-derived VEGF protects vessels from hyperoxia. ''']]

|}

==Useful Links==

{{External Links}}

[http://www.youtube.com/watch?v=Xme8PA6xv-M Visualisation of eye development in the embryo]

[http://www.embryo.chronolab.com/sense.htm Embryonic Development of the eye]

==Glossary==

'''Accommodation''' - changing the focal length of the lens in order to focus on an object.

'''Downstream genes''' - genes that are activated by other "upstream genes".

'''Ectoderm''' - outermost layer of germ cells in an early embryo.

'''Endoderm''' - innermost layer of germ cells in an early embryo.

'''Glial cells''' - non-neuronal cells that provide structure and protection to neurons as well as producing myelin.

'''Inductive signaling''' - a process whereby the secretion of factors from one cell or tissue triggers a response in another.

'''Lens vesicle''' - the cavity of invaginated ectoderm from the optic placode that will form the lens.

'''Macula''' - a highly pigmented, oval-shaped area located near the centre of the retina. Important for visual acuity.

'''Mesenchyme''' - undifferentiated, loose connective tissue.

'''Mesoderm''' - middle layer of germ cells in an early embryo.

'''Mesothelium''' - the epithelial layer of the mesoderm.

'''Myelinisation''' - development of a myelin sheath around a nerve fibre.

'''Neural crest''' - a portion of the ectoderm situated next to the neural tube.

'''Neural groove''' - a large invagination on the dorsal surface of the embryo which will close off and form the neural tube.

'''Neural tube''' - hollow structure that results from the folding of the neural plate and eventually forms the central nervous system.

'''Neuroblastic layer''' - a layer of immature cells that differentiate to form either glial cells or neurons. The retina has two of these (an inner and outer).

'''Neuroectoderm''' - portion of the ectoderm that develops to form the central and peripheral nervous systems.

'''Optic chiasm''' - the point at which the optic nerves meet and cross over.

'''Optic cup''' - the structure that is formed after the optic vesicle folds in upon itself. This will form the retina.

'''Optic globe''' - a term that refers to the optic cup, lens vesicle and surrounding mesenchyme collectively.

'''Optic placode''' - area of thickened ectoderm that gives rise to the lens of the eye.

'''Optic stalk''' - a long, narrow cavity that will produce the optic nerve.

'''Optic vesicle''' - a cavity that buds off from the neural tube and gives rise to the optic cup.

'''Upstream genes''' - genes that activate one or more other "downstream genes".

'''Vascularise''' - to invade with blood vessels.

==Image Gallery==
<gallery>
Image:Eye_diagram_bandw.jpg‎ | Basic structure of the human eye.
Image:Stage14 sem2b-limb.jpg | A Stage 14 embryo showing the location of an otic placode.
Image:Stage 13 image 060.jpg | A cross section showing the organisation of the developing brain, the optic vesicle and the lens (optic) placode.
Image:Formation of the optic vesicle 1.jpg | Early formation of the optic vesicle from the neural groove.
Image:Formation of the optic vesicle 2.jpg | The optic vesicle at a later stage, showing the optic stalk.
Image:Formation of the optic nerve and chiasm 1.jpg | A recognisable brain and eye structure in later development.
Image:Formation of the optic cup 1.jpg | Mechanism of optic cup formation.
Image:Formation of the optic cup 2.jpg | Layers of the optic cup in retina development.
Image:Formation of the retina 1.jpg | Cross-section of the primitive retina showing cell types and layers.
Image:Formation of the retina 2.jpg | Cross-section of a developed retina showing cell types and layers.
Image:Formation of the lens 1.jpg | The importance of the optic cup in lens differentiation.
Image:Formation of the lens 2.jpg | The lens placode separates from the ectoderm and migrates into the mesoderm forming the lens vesicle.
Image:Formation of the choroid and sclera 1.jpg | The choroid and sclera derives from mesenchyme surrounding the optic cup.
Image:Formation of the eyelid 1.jpg | Small grooves in the ectoderm of the head - the precursors to an eyelid.
Image:Formation of the eyelid 2.jpg | The eye at an advanced stage of embryonic development. Note however, that the eyelids remain fused until much later.

</gallery>

==References==
<references/>

----

--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

----

{{2012Projects}}

2012 Group Project 1

2012-10-02T13:25:04Z

Z3254758: /* Development, Structure and Function of Ocular Components */

[[File:Eye_collage_2.jpg|right|830px]]

=Vision Development=

==Introduction==

Eyes are an important sensory organ shared across many different species and allow organisms to gather useful visual information from their environment. The visual system uses light from the environment and processes this information in the brain for visual perception. The visual system is complex, and is made up of various structures that work together to form vision. Each of the structures in the eye have specific tasks which contribute to the visual system. Knowledge of how the eye develops extends as far back as Aristotle more than 2000 years ago, and current knowledge shows that most of the crucial events of eye development occur in the embryological stage. The eye is an interesting model for studying the development of tissues in organisms, as it consists of cells from several parts of the embryo including the head ectoderm, neural ectoderm and mesoderm. From its many origins the cells come together and differentiate to produce the complex organ that is the eye. During this period there are many examples of inductive signaling, as the tissues coordinate their development throughout this elegant process.

The main anatomical structures of the eye are as follows:
{|
|
* Cornea

* Sclera

* Choroid

* Iris

* Ciliary body

* Lens

* Anterior chamber

* Posterior chamber

* Retina

* Optic nerve

|[[File:eye_diagram_bandw.jpg|right|250px|thumb|Basic structure of the human eye.]]
|}
[[File:Eyediagramcolour1.JPG|550px]]

==Research History==

=== '''Brief Timeline of Historical Developments on the Eye and its Embryology''' ===

{| width=800px
|-bgcolor="CEDFF2"
| width=100px|'''Time'''
| width=700px|'''Discovery'''

|-bgcolor="F5FAFF"
| '''Ancient Egyptians'''
| First to document cataracts. It is described as being 'the white disease of the eye' or 'darkening of the pupil.' <ref>Edwards, D.D. (1996). Ophthalmology before Hippocrates. In the History of Ophthalmology, ed. D.M. Albert and D.D. Edwards. Cambridge, Mass.: Blackwell Science.</ref> The Egyptians had some knowledge of the eye, however it is not known how much of the anatomy of the eye was known in their era.

|-bgcolor="CEDFF2"
| '''535 BC'''

|
Ancient Greek philosopher Alcmaeon conducted dissection of humans for the first time in recorded history. This included dissection of the eye. However, not much is known about which anatomical features he discovered. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17.">Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17.</ref>

|-bgcolor="F5FAFF"
| '''384- 322 BC'''

| [[File:Aristotle-eye.jpg|200px|thumbnail|The eye according to Aristotle.<ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "> Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau </ref> Note the lens is missing, and there are three vessels drawn that was believed to transport fluid to and from the eye.<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
]]
Aristotle performed dissections of animal embryos.<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

When Aristotle described the embryo of a ten day old chicken, he wrote "The eyes about this time, if taken out, are larger than beans and black; if their skin is removed the fluid inside is white and cold, shining brightly in the light, but nothing solid." <ref name="Magnus, H. (1998). Ophthalmology of the ancients. In J. Hirschberg (Ed.), The History of Ophthalmology: The monographs, Vol. 4, Part 1 (F.C. Blodi, Trans.) Bonn: Wayenborgh.">Magnus, H. (1998). Ophthalmology of the ancients. In J. Hirschberg (Ed.), The History of Ophthalmology: The monographs, Vol. 4, Part 1 (F.C. Blodi, Trans.) Bonn: Wayenborgh.</ref>

Aristotle believed that the eyes started forming during early embryogenesis, however, he also believed that the eyes are the last organs to form completely, and he incorrectly thought that the eyes shrink in later embryonic development. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press.">Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press.</ref> .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"

| '''340 BC'''

| Lens is thought to have been discovered by Hippocrates, due to his descriptions of the contents of the internal eye There has been studies in chick development later on by followers of Hippocrates. They claimed that eyes were visible in early embryogenesis. .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
|-bgcolor="F5FAFF"
|'''25 BC - 50 AD'''

| [[File:Celsus-eye.jpg|150px|thumb|The eye according to Celsus. <ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "/>
Note the lens is placed in the centre of the eye, in the vitreous.<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> ]]

Aulus Cornelius Celsus wrote a Roman medical text called 'De Medicina' in which he wrote that the lens was the part of the eye from which vision originated. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.">Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.</ref> Celsus also incorrectly drew the lens in the center of the globe in his diagram of the eye. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

|-bgcolor="CEDFF2"
| '''23-79 AD '''
|
Pliny the Elder said that the eye is the last of the organs to develop in the womb <ref name="Magnus, H. (1998). Ophthalmology of the ancients. In J. Hirschberg (Ed.), The History of Ophthalmology: The monographs, Vol. 4, Part 1 (F.C. Blodi, Trans.) Bonn: Wayenborgh."/>
|-bgcolor="F5FAFF"
| '''98-117 AD'''

| [[File:Rufus-eye.jpg|150px|thumb|The eye according to Rufus of Ephesus. <ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "/>
Note the lens is placed in the correct position, behind the iris of the eye <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> ]]

Rufus of Ephesus identified the lens as being located in the anterior part of the eye, close to the pupil. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

His diagram illustrates that he knew the correct position of the lens as being directly behind the iris, in the anterior part of the eye, and not in the centre as was previously depicted by others before him.

|-bgcolor="CEDFF2"
| '''130-200 AD'''

| [[File:Galen-eye1.jpg|150px|thumb|The eye according to Galen. <ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "/> ]]

Claudius Galen practised medicine in Rome. He wrote:

"1. Within the eye the principal orgran of sensation is the crystalline lens.

2. The sensation potential comes from the brain and is conducted via the optic nerves.

3. All other parts of the eyeball are supporting structures." <ref> Hirschberge, J. (1982). Antiquity, Vol. X in the History of Ophthalmology (F.C. Blodi, Trans.) Bonn: Wayenborgh. pp. 280 </ref>

Galen thought that the lens was produced from the vitreous. He also believed that the retina’s function was to give nourishment to the lens and vitreous, and to carry visual information to the brain from the lens. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

|-bgcolor="F5FAFF"

| '''1514-1564'''

| Andreas Vesalius published his anatomy book "De Humani Corporis Fabrica in 1543. He had the misconception that the lens was located in the centre of the eyeball. .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> He also wrote that the lens functioned "like a convex lens made of glass" <ref name="Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.">Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.</ref> pp. 48
|-bgcolor="CEDFF2"
| '''1535-1606'''

| Georg Bartisch correctly drew a diagram of the lens placed behind the iris in his book 'Ophthalmodouleia: das ist Augendienst'. <ref name="Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>
|-bgcolor="F5FAFF"

| '''1537-1619'''

| Fallopio Hieronymus Fabricius ab Aquapendente studied anatomy and embryology. He studied chicken embryos, and thought that chalazae (which comes from egg white) gives rise to the eyes. He also drew the lens directly behind the iris in a diagram in is book 'Tractatus de Oculo Visuque Organo. <ref name="Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

|-bgcolor="CEDFF2"
| '''1583'''

| Felix Platter published his book 'De corporis Humani Structura et Usu, after he performed dissections of human bodies. He believed that the retina is the primary visual organ in the eye. .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="F5FAFF"
| '''1619'''
| Scheiner is given credit to be the first person to correctly draw the diagram of the anatomy of the eye. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
|-bgcolor="CEDFF2"
| '''1672'''
| Marcello Malpighi described the embryonic development of the chicken. He drew many detailed diagrams of the chick eye. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1665'''
| Nicolaus Steno identified the choroid fissure in his study of a developing embryo of a chicken. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="CEDFF2"
| '''1754'''

| Albrecht von Haller studied the embryology of the eye. With help from his student Johann Gottfried Zinn, he contributed to the understanding of the development of the ciliary body, ciliary zonule, and their relationship with the lens and vitreous. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1817'''

| Christian Pander discovered the three embryonic germ layers, which he wrote about in his book. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/> Pander was the first to think of 'the optic vesicles as lateral evaginations' of the 'prosencephalon'; however, he was incorrect about the details regarding how 'the eye develops from these evaginations'. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="CEDFF2"
| '''1828-1837'''

| Karl Ernst von Baer studied embryology. He discovered that the optic vesicles were 'outgrowths of the embryonic forebrain' <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> which he believed was caused by pressure from fluids in the central nervous system. Von Baer also believed that the optic vesicle opens to form the pupil, and that fluid in the optic vesicle coagulates to form the vitreous body and lens. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1830'''

| Emil Huschke discovered that the lens forms from the invagination of the surface ectoderm. He concluded that the lens hence does not form ‘from the fluid of the optic vesicle’ <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> as previously thought.
|-bgcolor="CEDFF2"
| '''1832'''

| Emil Huschke wrote in his manuscript ‘Ueber die erste Entwinkenlung des Auges und die damit zusammenhängende Cyklopie’ that the lens capsule forms from the outer surface ectoderm, which detaches and moves back inward, which is later enclosed again by several membranes, such as by the cornea. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

Huschke also described how the optic cup and choroid fissure forms. He discovered that the optic vesicles are produced from the two-layered optic cup. However, he incorrectly described the destiny of the ‘individual optic cup layers’. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

|-bgcolor="F5FAFF"
| '''1838'''
| Matthias Jakob Schleiden and Theodor Schwann formulated the ‘cell theory’: “All living things are formed from cells, the cell is the smallest unit of life, and cells arise from pre-existing cells.” <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
|-bgcolor="CEDFF2"
| '''1839'''

| Theodor Schwann contributed a better understanding of the development of the lens through studying the foetus of a pig, which he wrote about in his book ‘Mikroskopische Untersuchungen Über Die Uebereinstimmung in Der Struktur Und Dem Wachsthum Der Thiere Und Pflanzen’. He wrote that the lens is made of ‘concentric layers’ of fibres which proceeds from an anterior to posterior direction. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1842'''
| Robert Remak gave the current names to the three embryonic germ layers: ectoderm, mesoderm and endoderm. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"
| '''1843'''
| Wilhelm Werneck published his book ‘Beiträge zur Gewebelehre des Kristallkörpers’. He wrote that the contents inside of the lens is not made of fluids, as was previously believed. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/> Werneck also discovered that the fibers of the lens continues to grow from the outside to the centre during embryogenesis. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

|-bgcolor="F5FAFF"
| '''1855'''

| Robert Remak wrote his book ‘Untersuchungen über die Entwickelung der Wirbelthiere’. He wrote about what he discovered in his studies of the development of the eye in the embryos of chickens, frogs, and rabbits. He wrote very descriptively about the embryology of lens formation, amongst other topics. He discovered that the ectoderm gives rise to the lens placode. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

|-bgcolor="CEDFF2"
| '''1858'''
| Henry Gray published his book 'Anatomy, Descriptive and Surgical'. He had also previously studied the embryonic development of the optic nerve and retina of chickens.
|-bgcolor="F5FAFF"
| '''1877'''
| Paul Leonhard Kessler wrote about the embryonic development of the lens in mice in his book ‘Zur Entwickelung des Auges der Wirbelthiere. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"
| '''1891'''
| Vincenzo Colucci studied newts and discovered their ability to regenerate the lens.<ref> Tsonis, P. A. (2001). Regeneration of the Vertebrate Lens and Other Eye Structures. eLS. (Online Publication). DOI: 10.1038/npg.els.0001102 </ref>
|-bgcolor="F5FAFF"
| '''1892'''
| Dr. Oscar Hertwig published his book ‘Text-Book of the Embryology of Man and Mammals. <ref> Hertwig, O. Text-book of the embryology of man and mammals. S. Sonnenschein 1901. (Translated from the 3d German ed. by Edward L. Mark.) </ref> It contains a very detailed description of the development of the eye, according to the findings at that time. [http://embryology.med.unsw.edu.au/embryology/index.php?title=Book_-_Text-Book_of_the_Embryology_of_Man_and_Mammals_16-2#The_Development_of_the_Eye]
|-bgcolor="CEDFF2"
| '''1895'''
| Gustav Wolff also independently studied newts and discovered their ability to regenerate the lens. .<ref> Tsonis, P. A. (2001). Regeneration of the Vertebrate Lens and Other Eye Structures. eLS. (Online Publication). DOI: 10.1038/npg.els.0001102 </ref>

|-bgcolor="F5FAFF"

| '''1900'''
| Carl Rabl published his book ‘Uber den Bau und die Entwicklung der Linse’. He wrote about the development of the lens in mammals, fish, birds, reptiles, and amphibians. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"
| '''1901'''
| Hans Spemann published his findings from his experimental studies about the formation of the lens in the frog. He found that the optic cup needed to be in contact with the ectoderm for normal development of the eye. <ref> Spemann, H. (1901). Über Correlationen in der Entwicklung des Auges. Verhand. Anat. Ges. 15: 61-79. </ref> <ref> Saha, M. (1991). Spemann seen through a lens. In Gilbert, S. F. (ed.). A Conceptual History of Modern Embryology. Plenum Press, NY. pp. 91-108.</ref>
|-bgcolor="F5FAFF"
| '''1906'''
| Brown ‘s book “The Embryology Anatomy and Histology of the Eye” was published. It contained detailed descriptions of the embryonic development of the eye according to the knowledge current at that time, mainly based on observations from embryos of rabbits and chickens. <ref> Brown, E.J. (1906). The Embryology Anatomy and Histology of the Eye. Chicago: Hazlitt & Walker. 1906 </ref>

|-bgcolor="CEDFF2"
| '''1907'''

| John Clement Heisler published his book ‘A Text-book of embryology’. It contains a chapter detailing the embryonic development of the eye, according to the knowledge current at that time. The book’s copyright has expired, so it can be viewed free online: [http://archive.org/details/atextbookembryo01heisgoog]

Julius Kollman also published his book 'Atlas of the Development of Man'. It contained very detailed description and illustrations showing the embryonic development of the human according to the knowledge current at that time. His illustrations were reused by many others after his time and built upon for further refined understanding of the embryology of the human.

Here are examples of Julius Kollman's excellent illustrations showing eye development in various stages:

'''Formation of Primary Optic Vesicle:'''
<gallery>
File:Kollmann691.jpg|The blue part at the bottom is the endoderm. The pink middle layer is the mesoderm. The top yellow layer is the ectoderm. The fold labelled as 'augenfeld' is the place where the optic vesicle will form.
File:Kollmann692.jpg|The eye area (augenfeld) is a bowl shaped bulge still located on the side walls.
File:Kollmann693.jpg| The neural tube is shown after removal of all of the ectoderm and ventral organs, such as heart, gut tube, etc. The primary optic vesicle forms a slightly flattened hollow protrusion on the forebrain.
File:Kollmann694.jpg|The lateral surface of the primary optic vesicle is slightly depressed, showing the first sign of the emergence of the secondary optic vesicle
</gallery>

'''Development of Lens:'''

<gallery>
File:Kollmann695.jpg|The bulging lateral wall of the primary optic vesicle is covered by a fairly well demarcated lens plate, a direct continuation of the ectoderm. Between the optic vesicle and the lens pit are some flattened spindle-shaped cells. In the adjoining mesoderm are cross-sections of capillaries.
File:Kollmann697.jpg|The lens still hangs together with the ectoderm. The primary eye vesicle is indented with respect to the lens. Between the lens and the lateral plate of the optic vesicle is a narrow space, which allows area to further develop later.
File:Kollmann698.jpg|4th Week of development. The internal organisation shows the secondary optic vesicle. A: The rear wall of lens is noticeable and is enveloped by mesoderm. B: The edges of the lens pit is already grown and the lens vesicles are formed, which is still related to the remaining ectoderm.
File:Kollmann699.jpg|The lens has now cut off from the ectoderm, but is still very superficial. Between it and the lateral lamina of the optic cup, there is a considerable space. The eye stalk has become longer and is enclosed together with the optic cup and lens of the mesoderm. The cornea, sclera and choroid make gradual development.
</gallery>

|-bgcolor="F5FAFF"

| '''1921'''
| Bailey and Miller published their textbook “Text-Book of Embryology “. <ref> Bailey, F.R. and Miller, A.M. (1921). Text-Book of Embryology. New York: William Wood and Co. (Note- This book is only at an early edited stage)</ref> It contains detailed description of the development of the embryonic eye according to the knowledge current at that time. [http://embryology.med.unsw.edu.au/embryology/index.php?title=Book_-_Text-Book_of_Embryology_18]

|-bgcolor="CEDFF2"
| '''1925'''

| Mann published his research article, in which he gives a detailed account of the development of the human iris. He divided the development of the iris into four stages: weeks 4-7 (before the ectodermal iris forms or before the anterior chamber forms); weeks 7-11 (anterior chamber appears, and mesodermal iris forms); weeks 11-12 (ectodermal iris forms); 3-8 months (muscles of the pupil forms from ectodermal iris, and the central portion of the mesodermal iris atrophies to make the pupil clear). <ref name="PMID18168466"><pubmed>18168466</pubmed></ref>
O Leser also published an article detailing the development of extraocular muscles in mammals he studied. <ref name="PMID18168498"><pubmed>18168498</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1939'''
| Holtfreter <ref> Holtfreter, J. (1939). Gewebeaffinitat, ein Mittel der embryonalen
Formbildung. Arch. Exp. Zellforsch. 23, 169-209. </ref> studied amphibians and observed that that the development of the eye stops at the ‘optic vesicle stage’ if there is no contact ‘with the epidermis and neural crest driven mesenchyme’. <ref name=”PMID11023863”><pubmed>11023863</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1955'''
| Barber published his book ‘Embryology of the human eye’. <ref> Barber AN: Embryology of the human eye. St. Louis. CV Mosby 1955</ref> In contains detailed descriptions of the embryological development of the human eye according to the knowledge current at that time. It contains many photographs of the eye at different stages of development.

|-bgcolor="F5FAFF"
| '''1957'''
| Coulombre studied a chicken embryo to find the role of intraocular pressure in the development of the chick’s eye, especially in regards to its control of the size of the eye structures. <ref name="PMID13469954"><pubmed>13469954</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1958'''
| Coulombre studied the development of the cornea and how it develops its transparency. <ref name="PMID13563560"><pubmed>13563560</pubmed></ref> He also studied the development of corneal curvature. <ref name="PMID 13519969"><pubmed> 13519969</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1962'''
| Coulombre studied the development of the conjunctival papillae and scleral ossicles. <ref name="PMID 14023393"><pubmed> 14023393</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1963'''
| Coulombre studied the development of lens fibers and their orientation. <ref name="PMID14077035"><pubmed>14077035</pubmed></ref> He also studied the development of pigmented epithelium. <ref name="PMID14023394"><pubmed>14023394</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1964'''

| Coulombre further studied the development of the lens to determine the role of the lens in eye growth. <ref name="PMID14189921"><pubmed>14189921</pubmed></ref> He also studied the role of thyroid in the development of the cornea and the development of corneal transparency. <ref name="PMID14211912"><pubmed>14211912</pubmed></ref> Mann also published his work called ‘The development of the human eye’, which contains detailed description of the embryonic development of the eye according to current knowledge at that time. <ref> Mann I. The development of the human eye. New York: Grune and Stratton 1964</ref>

|-bgcolor="CEDFF2"
| '''1965'''
| Coulombre published his findings regarding the regeneration of the neural retina from pigmented epithelium in the embryo of chickens. <ref name="PMID5833111"><pubmed>5833111</pubmed></ref> Smelser also published his findings on the embryological development and morphology of the lens. <ref name="PMID14340157"><pubmed>14340157</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1966'''

| Formation of the face and orbit occurs from the differentiation of neural crest cells. <ref name="PMID5969670"><pubmed>5969670</pubmed></ref> O’Rahilly also published findings of the development of the eye in the early stages of human embryos. <ref> O'Rahilly, R. 1966 The early development of the eye in staged human embryos. Contr. Embry. Carnegie Inst., Wash., 38: 1–42</ref>

|-bgcolor="CEDFF2"
| '''1968'''
| Findings of the postnatal development of the retina of rats was published. <ref name="PMID5640327"><pubmed>5640327</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1969'''

| Mann again published his work called ‘The development of the human eye’. He stated that that the lens in humans forms completely from the ectoderm. <ref name=”Mann I. The Development of the Human Eye. New York, USA: Grune & Stratton, Inc; 1969”> Mann I. The Development of the Human Eye. New York, USA: Grune & Stratton, Inc; 1969</ref> Coulombre also studied the development of the lens, and took note of its size, shape and orientation throughout its developmental stages. <ref name="PMID 5772716"><pubmed> 5772716</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1970'''
| Coulombre again further studied the regeneration of the neural retina from pigmented epithelium of embryos of chickens. <ref name="PMID 5472476"><pubmed> 5472476</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1971'''

| Coulombre further studied the development of the lens. This time he focused on analysing the histological mechanisms in the reconstitution of the lens from implanted lens epithelium. <ref name="PMID 4925671"><pubmed> 4925671</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1973'''
| A research article was published, detailing the embryonic development of the retina of humans. <ref name="PMID 6650859"><pubmed> 6650859</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1976'''

| Geeraets published his observations of the closure of the embryonic optic fissure in golden hamsters, using the electron microscope. <ref name="PMID 1266776"><pubmed> 1266776</pubmed></ref> Kornneef also published an article based on his studies of the development of connective tissue in the human orbit. <ref name="PMID 1020699"><pubmed> 1020699</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1981'''
| A research article was published detailing how myelin forms in the optic nerve of humans. <ref name="PMID 7224936"><pubmed> 7224936</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1983'''
| O’Rahilly’s further research developments was published, reporting the timing and sequence of events in the development of the embryonic human eye. <ref name="PMID 6650859"><pubmed> 6650859</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1990'''

| Van Driell et al. <ref>Driell, D. Van; Provis, J.M.; Billson, F.A.: Early differentiation of ganglion, amacrine, bipolar and Muller cells in the developing fovea of the human retina. J. Comp. Neurol. 291: 203-219.</ref> studied the manner in which amacrine, bipolar, retinal ganglion cells, and Muller cells differentiate in the developing fovea of the retina of a 15-week old human foetus. <ref name="PMID1628748"><pubmed>1628748</pubmed></ref> Tripathy also published an article providing evidence that the lacrimal glands in humans originates from the neuroectoderm. <ref name="PMID2406219"><pubmed>2406219</pubmed></ref>

|}

==Development, Structure and Function of Ocular Components==

The eye itself is formed from several components; notably the optic placode of the head ectoderm, the optic vesicle from the neural tube, and mesenchyme from the mesoderm and neural crest cells. The optic placode contributes the lens to the eye, the optic vesicle gives rise to layers of the retina, while the mesenchyme will produce the ciliary body, iris, choroid and sclera.<ref>http://www.vetmed.vt.edu/education/curriculum/vm8054/eye/EMBYEYE.HTM</ref> Cells from the neural tube will also produce the optic nerve, which receives nerve impulses from the retina of the eye. Eyes initially form as laterally paired structures and migrate medially in the human embryo. In other animals such as birds and lizards, the eyes do not migrate and develop laterally on the head. The optic placodes become prominent on the surface of the embryo at approximately Stage 14 of development.

[[File:Stage14 sem2b-limb.jpg|200px|thumb|left|A Stage 14 embryo showing the location of an otic placode.<ref name="http://embryology.med.unsw.edu.au/embryology/index.php?title=ANAT2341_Lab_6_-_Early_Embryo">http://embryology.med.unsw.edu.au/embryology/index.php?title=ANAT2341_Lab_6_-_Early_Embryo</ref>]] [[File:Stage 13 image 060.jpg|400px|thumb|center|A cross section showing the organisation of the developing brain, the optic vesicle and the lens (optic) placode.<ref name="http://embryology.med.unsw.edu.au/embryology/index.php?title=ANAT2341_Lab_6_-_Early_Embryo"/>]]

Pax6 and Pax6(5a) isoforms are essential for the normal development of the eye. Over or under expression can both lead to major structural abnormalities<ref><pubmed>18386822</pubmed></ref>.

===Optic Nerve===

The optic nerve consists of nerve fibres that transmit information from the retinal photoreceptor cells to the brain. The optic nerve is formed from the optic stalk, which develops as the optic vesicle migrates from its origin in the neural tube to its destination - the surface ectoderm - where it will fuse with the optic placode (also known as the lens placode, which will contribute the lens to the eye).<ref name="PMID11687490"><pubmed>11687490</pubmed></ref>

[[File:Formation of the optic vesicle 1.jpg|400px|thumb|left|Fig. 1: Early formation of the optic vesicle from the neural groove.]] [[File:Formation of the optic vesicle 2.jpg|400px|thumb|center|Fig. 2: The optic vesicle at a later stage, showing the optic stalk.]]

As can be seen in Figure 1 above, the optic vesicle forms from the neural tube. However, note that the neural tube has not yet closed, and is still the neural groove at this point. Figure 2 then shows the optic vesicle at slightly later stage in the same simplified cross-section of the embryo, as it migrates from the neural tube to the surface ectoderm. Note the presence of the optic stalk which links the optic vesicle to the neural tube. Later in development, this primitive structure will become the optic nerve, which will link the eye to the brain.

The nerve fibres themselves will initially originate from the retinal ganglion cells in the eye during week 6.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008">Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008</ref> After two weeks, these fibers will have grown along the inner wall of the optic stalk and have reached the brain. They grow both in length and width, with the nerve fibres filling the hollow optic stalk to form the solid optic nerve. More than one million nerve fibers will eventually make up the optic nerve, along with glial cells which arise from the inner wall of the optic stalk itself.<ref><pubmed>1451666</pubmed></ref> Myelinisation of the optic nerve begins much later in development at around 7 months, beginning at the optic chiasm and moving towards the eye.<ref><pubmed>7224936</pubmed></ref> The optic chiasm forms just before the nerves reach the brain, and is where half the nerve fibres from each eye will cross over to the opposite side of the brain. This is demonstrated in Figure 3. Note the crossing over of the optic nerves just before they enter the brain, at the optic chiasm. This organisation is now much more familiar, with the eyes near the ectoderm and the optic nerve leading through the mesoderm to the brain buried deep in the embryo.

[[File:Formation of the optic nerve and chiasm 1.jpg|400px|thumb|center|Fig. 3: A recognisable brain and eye structure in later development.]]

===Retina===

The retinal component of the eye is formed when the optic vesicle folds in upon itself, forming the optic cup (see Figure 4). In doing so it creates two layers - an inner wall and an outer wall of the optic cup (Figure 5). These two layers of the optic cup will give rise to the two layers of the retina - the inner neural retina, and the outer pigmented epithelium.<ref name="PMID11687490"/> Note the existence of the space between the two layers of the retina. This is known as the intraretinal space and disappears by the 7th week of development, however the two layers never completely fuse and can become separated as a result of physical trauma to the head - leading to a detached retina and loss of vision.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/>

The inner wall of the optic cup, which will give rise to the neural retina, consists of a layer of pseudostratified cells (see Figure 6) that later differentiate into rod, cone, bipolar, ganglion, horizontal, amacrine and glial cells of the retina (Figure 7).<ref name="PMID18168748"><pubmed>18168748</pubmed></ref> The outer wall of the optic cup consists of a layer of cuboidal cells that contain melanin - the light absorbing pigment. The function of this layer is to absorb light and prevent internal reflection of light within the eye, which would impair our ability to form distinct images. Interestingly, in some animals such as cats, this layer actually reflects light intentionally to increase the amount of light available to the eye in low-light conditions. This is why cats seem to have eyes that glow in the dark.<ref>http://dialspace.dial.pipex.com/agarman/bco/fact4.htm</ref>

[[File:Formation of the optic cup 1.jpg|400px|thumb|left|Fig. 4: Mechanism of optic cup formation.]] [[File:Formation of the optic cup 2.jpg|400px|thumb|center|Fig. 5: Layers of the optic cup in retina development.]]

The inner wall itself is divided into two components - the inner neuroblastic layer and the outer neuroblastic layer (see Figure 6). The outer neuroblastic layer forms the rod and cone cells while the inner neuroblastic layer forms the remaining cell types found in the retina - the bipolar, ganglion, horizontal, amacrine and glial cells (Figure 7).<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/> The organisation of the retina is interesting in that incoming light passes through several layers of these neural retina cells before it is detected by rod and cone cells at the back of the retina, and then nerve signals are passed back through the layers of neural retina cells that the light just passed through moments before - a seemingly strange design that the eye does not share with man-made light-capturing devices such as a camera (imagine putting the wires in front of the image sensor!).

Differentiation of the neuroblastic layers into neural retina cells occurs in a pattern both within the layers and across the retina. Cells differentiate from the inner neuroblastic layer to the outer neuroblastic layer, and differentiate from the central retina to the peripheral retina.<ref name="PMID18168748"/> The macula is first identifiable in week 22 when ganglion cells start to form multiple rows, and the primitive fovea begins to form at approximately the same time as a depression in the macula.<ref><pubmed>6462623</pubmed></ref> It is not until 15-45 months after birth that this area becomes exclusively populated by cone cells and becomes the fovea centralis - the area of the retina with the highest visual acuity.

[[File:Formation of the retina 1.jpg|400px|thumb|left|Fig. 6: Cross-section of the primitive retina showing cell types and layers.]] [[File:Formation of the retina 2.jpg|400px|thumb|center|Fig. 7:Cross-section of a developed retina showing cell types and layers.]]

===Ciliary Body===

The ciliary body consists of ciliary processes and three portions of fibres that constitute the ciliary muscles. It functions to maintain normal eye physiology as well as playing a direct role in accommodation.

During development, the ciliary processes form slightly posterior to the iris, developing from part of the anterior rim of the optic cup. It is thought that the folded structure of the ciliary processes is brought about by intraocular pressure and specific signalling pathways.<ref name="PMID16959249"><pubmed>16959249</pubmed></ref> While the ciliary muscles and the endothelial cells of the ciliary blood vessels are chiefly formed by mesenchymal cells<ref><pubmed>16249499</pubmed></ref>, the neural crest and neuroectoderm also contribute to their development.<ref><pubmed>12127103</pubmed></ref> The normal development of the ciliary body is dependent on the correct expression of bone morphogenetic protein (BMP)-4, which is a member of the transforming growth factor-β superfamily.<ref><pubmed>1222340</pubmed></ref> Napier and Kidson (2007) summarised numerous genes that have been associated with ciliary body development, however their direct roles have not been well documented.<ref name="PMID16959249"/>

===Iris===

The iris is a thin layer that develops at the end of the third month of development and is derived from the anterior rim of the optic cup. The stroma of the iris develops from cells of neural crest cell origin.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/> The muscles that are responsible for the dilation and constriction of the pupil (dilator pupillae and sphincter pupillae muscles) form from the neuroectoderm of the optic cup. These cells are initially epithelial cells that then transform into smooth muscle cells. <ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"></ref>. The invagination of the optic vesicle which creates the optic cup, also causes the formation of the optic cup lip. This is the region of the where the epithelium doubles back, separating the outer pigmented layer and the inner nonpigmented layer. This is the edge of the iris that borders on the pupil<ref><pubmed> Retinal and anterior eye compartments derive from a common progenitor pool in the avian optic cup</pubmed></ref>.

The final colour of the iris is not evident until the postnatal period. It is determined by a number of genes including IRF4, SLC24A4 and MATP<ref><pubmed>19710684</pubmed></ref>. Other features such as crypt frequency, furrow contractions, presence of peripupillary pigmented ring, and number of nevi also become evident during development<ref><pubmed>21835309</pubmed></ref>.

Mutations in Pax6 have been shown to cause partial or complete loss of the iris <ref><pubmed>12386935</pubmed></ref>.

===Cornea===

The cornea is the transparent, avascular, most anterior portion of the eye. It is responsible for conducting light into the eye and focusing it on to the retina, as well as maintaining the rigidity of the eyeball. It consists of 5 layers- the epithelium, Bowman’s layer, stroma, Descemet’s membrane and the endothelium.

The epithelium and endothelium of the cornea first appear during the 5th week of gestation. The epithelium of the external surface of the cornea is derived from surface ectoderm, while the mesenchyme is derived from the mesoderm<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"/>. The endothelium is a two-cell cuboidal layer which is made up of differentiated neural crest cells that were initially from the optic cup. By week 8 the endothelial cells begin to secrete a basement membrance which later forms Descemet’s membrane<ref><pubmed>6511224</pubmed></ref>. At approximately 16 weeks gestation the Bowman’s membrane begins to form from the thickening of the stroma that is located under the corneal epithelium<ref>Riordan-Eva P, Whitcher JP. Vaughn and Asbury's General Ophthalmology, Lange Medical Books/McGraw Hill. 2004:25–27</ref>. During the third month glycosaminoglycans secreted by fibroblasts form the ground substance of the cornea, with collagen fibrils and keratan sulphate also appearing around this time. Shortly after this tight junctions form between the endothelial cells<ref><pubmed>19481138</pubmed></ref>. Fibroblast growth factor causes the epithelial cells to proliferate<ref><pubmed>20105280</pubmed></ref>.

Towards the end of the gestational period the cornea becomes larger due to the production of aqueous humor<ref>Yanoff M, Duker JS. Ophthalmology. Mosby; St. Louis, MO: 2004</ref>. The final transparent structure develops because hyaluronidase removes hyaluronic acid, thyroxine causes dehydration of the stroma, and the entire structure becomes avascular<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/>. Numerous genes have been implicated in the development of the cornea, these include, but are not limited to, PAX6, PITX2, FOXC1, MAF, TMEM114, SOX2, OTX2 and BMP4<ref><pubmed>18637741</pubmed></ref>.

===Lens===

The lens has its origin from the optic placode, which develops on the ectodermic surface of the embryo and migrates both medially and inwards into the embryo. The lens allows accommodation of the eye, and adjusts its thickness in order to focus on near or far objects. The study of lens development was one of the first to highlight the importance of inductive signaling in development, with Spemann's pioneering work at the start of the 20th century, finding that the absence of retinal development resulted in the absence of lens formation.<ref name="PMID11687490"/> Indeed, it has been consistently shown that the interaction of the migrating optic vesicle with the surface ectoderm of the head is vital in producing differentiation of the lens.<ref name="PMID15558475"><pubmed>15558475</pubmed></ref> The mechanism of interaction is complex but basically involves upstream genes switching on downstream genes, with the genes eventually producing specialised proteins which constitute the lens. The whole process starts with the signaling molecules from the optic cup initiating a thickening of the surface ectoderm of the head (Figure 8). It is thought that this region of specific ectoderm is responsive to the signaling molecules, as lens formation is incomplete or absent when ectoderm from the lateral portion of the embryo (i.e. non-head ectoderm) is exposed to the same inductive signaling processes.<ref name="PMID9216064"><pubmed>9216064</pubmed></ref> Pax6 has been shown to be one of the major genes required for differentiation of the lens, which in turn switches on transcriptional genes such as Sox 1, 2 and 3 among others - producing water-soluble proteins called crystallins - responsible for giving the lens its transparency and refractive properties.<ref name="PMID9609835"><pubmed>9609835</pubmed></ref>

[[File:Formation of the lens 1.jpg|400px|thumb|left|Fig. 8: The importance of the optic cup in lens differentiation.]] [[File:Formation of the lens 2.jpg|400px|thumb|center|Fig. 9: The lens placode separates from the ectoderm and migrates into the mesoderm forming the lens vesicle.]]

The lens placode invaginates from the head ectoderm and migrates into the mesoderm (Figure 9). Once this structure (now known as the lens vesicle) is in place opposite the optic cup, the combined structure is referred to as the optic globe and resembles a recognisable eye structure. The lens continues to differentiate further, as mentioned above, through the formation of crystallin proteins, which give the lens its unique properties and allows for the fine control over the degree of refraction that takes place.

===Aqueous Chambers===

There are both anterior and posterior aqueous chambers of the eye which contain aqueous humour. A space develops in the mesenchyme situated between the lens and cornea to form the anterior aqueous chamber. The mesenchyme located superficially to this chamber forms the mesothelium as well as the transparent portion of the cornea.

The posterior chamber develops from a similar space in the mesenchyme, however it is located between the iris and the lens. The anterior and posterior chambers are able to communicate with one another once the papillary membrane vanishes and the pupil is formed. This channel is known as the scleral venous sinus.<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011">Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011</ref>

Contained within the aqueous chambers is aqueous humor. The production of aqueous humor is dependant on the development of the ciliary body. It is produced in the ciliary processes and it’s production is a metabolic process driven by the delivery of oxygen and the removal of wastes via the ciliary circulation<ref><pubmed>20801226</pubmed></ref>.

===Cornea===

The cornea is the transparent, avascular, most anterior portion of the eye. It is responsible for conducting light into the eye and focusing it on to the retina, as well as maintaining the rigidity of the eyeball. It consists of 5 layers- the epithelium, Bowman’s layer, stroma, Descemet’s membrane and the endothelium.

The epithelium and endothelium of the cornea first appear during the 5th week of gestation. The epithelium of the external surface of the cornea is derived from surface ectoderm, while the mesenchyme is derived from the mesoderm<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"/>. The endothelium is a two-cell cuboidal layer which is made up of differentiated neural crest cells that were initially from the optic cup. By week 8 the endothelial cells begin to secrete a basement membrance which later forms Descemet’s membrane<ref><pubmed>6511224</pubmed></ref>. At approximately 16 weeks gestation the Bowman’s membrane begins to form from the thickening of the stroma that is located under the corneal epithelium<ref>Riordan-Eva P, Whitcher JP. Vaughn and Asbury's General Ophthalmology, Lange Medical Books/McGraw Hill. 2004:25–27</ref>. During the third month glycosaminoglycans secreted by fibroblasts form the ground substance of the cornea, with collagen fibrils and keratan sulphate also appearing around this time. Shortly after this tight junctions form between the endothelial cells<ref><pubmed>19481138</pubmed></ref>. Towards the end of the gestational period the cornea becomes larger due to the production of aqueous humor<ref>Yanoff M, Duker JS. Ophthalmology. Mosby; St. Louis, MO: 2004</ref>. The final transparent structure develops because hyaluronidase removes hyaluronic acid, thyroxine causes dehydration of the stroma, and the entire structure becomes avascular<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/>. Numerous genes have been implicated in the development of the cornea, these include, but are not limited to, PAX6, PITX2, FOXC1, MAF, TMEM114, SOX2, OTX2 and BMP4<ref><pubmed>18637741</pubmed></ref>.

===Choroid and Sclera===

The choroid and sclera are adjacent layers that surround the eye and act to vascularise and protect the eye respectively. They are formed from neural crest and mesoderm-derived mesenchyme which condenses around the optic cup and lens vesicle between weeks 5 and 7 of development to form a primitive eyeball structure known as the optic globe.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/> Blood vessels first start to appear in the choroid layer at approximately week 15, and arteries and veins can be distinguished by week 23.<ref>Development of the Choroid and Related Structures, K. Sellheyer, Eye (1990) 4, 255-261</ref> Inductive processes are thought to play a vital role during formation of the choroid and sclera; with the retinal pigmented epithelium inducing differentiation of the surrounding mesenchyme while at the same time the neural crest-derived mesenchyme contributing components to the retinal pigmented epithelium such as melanocytes.<ref name="PMID1628748"/> In addition to having functional roles themselves, the primitive choroid and sclera also contribute components to the developing ciliary body and cornea (Figure 10). In the adult eye, the choroid is continuous with the ciliary body and the sclera with the cornea.

[[File:Formation of the choroid and sclera 1.jpg|400px|thumb|center|Fig. 10: The choroid and sclera derives from mesenchyme surrounding the optic cup.]]

===Eyelids===

The eyelids are ectodermal and mesodermal in origin and are an extension of the skin which covers and protects the eye. Eyelid formation can be first noted during week 5 when small grooves develop in the surface ectoderm (Figure 11).<ref><pubmed>7364662</pubmed></ref> These small grooves deepen and extend into the mesoderm and the primitive eyelid structures grow towards one another, eventually fusing together during week 8.<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"/> It is not until week 26-28 that the eyelids will separate again. The ectoderm reflects over the developing cornea to form the conjunctival sac, a space that is filled by secretions from the lacrimal gland in order to allow smooth motions of the eyelid over the eye and also to clean the cornea and prevent accumulation of particles on the eye that may disrupt vision. By the time the eyelids separate, the eye has all its major components present (Figure 12), and further development consists mainly of growth and vascularisation.

[[File:Formation of the eyelid 1.jpg|400px|thumb|left|Fig.11: Small grooves in the ectoderm of the head - the precursors to an eyelid.]] [[File:Formation of the eyelid 2.jpg|400px|thumb|center|Fig. 12: The eye at an advanced stage of embryonic development. Note however, that the eyelids remain fused until much later.]]

===Lacrimal Glands===

Lacrimal glands initially develop from budding of the conjunctival epithelium near the superolateral portion of the eye. The mesenchymal cells that surround these buds are of neural crest origin, and the budding continues until the mature gland is formed.<ref><pubmed> 9882499</pubmed></ref> These glands are responsible for the production of tears however they do not start to function until 1-3 months after birth.

==Current Research==

*more info will be added soon!!

===GABA Maintains the Proliferation of Progenitors and Non-Pigmented Ciliary Epithelium===

<pubmed>22590629</pubmed>

{| width=800px
|-
| width=450px|
| width=350px|

|-
| GABA is an ‘inhibitory neurotransmitter’ in the central nervous system of adults. <ref name="PMID22590629"><pubmed>22590629</pubmed></ref> It is responsible for controlling proliferation of stem cells and progenitor cells. The authors of this article <ref name="PMID22590629"/> was interested to find the effects of GABA on proliferation of progenitor cells and non-pigmented ciliary epithelial cells (NPE) in the retina. Their study focused on progenitor cells and non-pigmented epithelium of the ciliary body in chickens. Non-pigmented epithelial cells in chickens arise from the neuroepithelium of the optic cup. They share similar functions as progenitors of the early retina, such as expression of Chx10 and Pax6 genes. It is not agreed upon whether epithelial cells of the ciliary body have stem cell properties. However, it has been found that these cells can be cultured and transplanted into retinas that are injured, in order to replace neurons that were previously lost. However, there is not much known about what factors regulate the proliferation of stem cells. Hence the authors were interested in finding the effects of GABA on proliferation of retinal cells. Their results showed that non-pigmented epithelial cells in chickens ‘express extrasynaptic-like GABAA receptors’ that have the ability to regulate cell proliferation. It has been found that inhibiting these ‘GABAA receptors’ also causes a decrease in proliferation of retinal progenitor cells and non-pigmented epithelial cells in 'the intact E8 retina’. <ref name="PMID22590629"/>

|
[[File:Gaba-effects-retina.JPG|thumbnail|250px|'''GABAA receptor mediated effects on retinal progenitor cell proliferation'''
]]
|}

-------------------

===The impact of visible light on the immature retina===

<pubmed>22405869</pubmed>

The authors mentioned in this article <ref name="PMID22405869"><pubmed>22405869</pubmed></ref> that they were interested in investigating the effect of light on postnatal eye development in mice, because mice are born with fused eyelids, which separate 12 days after birth. Before the eyelids separate, the retina develops in mice with very little radiation from light. It is believed that the darkness plays a role in the development of the retina in mice, which is why their eyelids are fused for 12 days after birth. Therefore the authors were interested to see what effect light would have on postnatal retinal development of mice, with special interest in retinal ganglion cells (RGC). In their experiment, they surgically opened the eyelids on the right eyes of some of the mice to expose them to visible light 12 hours per day, while they left some other mice in the dark after surgical separation of their eyelids. They also kept the left eyes of the mice naturally fused as controls in the experiment. Their results showed that early light exposure in mice causes a decrease in retinal ganglion cells because it affects cellular apoptosis in the retina. The authors also observed that early exposure to light in mice causes lumican mRna transcription to resume and to quickly increase. (Lumican normally stays silent in retina after birth).

---------

===MIP/Aquaporin 0 Represents a Direct Transcriptional Target of PITX3 in the Developing Lens===

<pubmed>21698120</pubmed>

{| width=800px
|-
|PITX3 plays a siginificant role in the development of lens in vertebrates. If there is a deficiency is PITX3, it causes a range of problems in humans such as microphthalmia, Peter’s anomaly, or isolated cataracts. Mutation of PITX3 also causes degeneration of the lens in zebrafish and mice. It is therefore important to understand what factors may affect the decrease in PITX3, as a normal level of PITX3 is needed to maintain normal eye development. The authors wanted to investigate specific genes which are affected by PITX3. Previous research has shown that MIP and Aquaporin causes defects in the lens in both mice and humans. MIP and Aquaporin are targeted by PITX3, so their imbalance is interrelated in the cause of defects in the lens. Therefore it has been previously proven that PITX3 is needed for normal development of the lens. However, there has not been much information previously known regarding the exact effect that PITX3 has, or the specific genes it targets. Since MIP and Aquaporin is common genes found in humans, mice and zebrafish, the authors <ref name="PMID21698120"><pubmed>21698120</pubmed></ref> chose to study these genes to understand the pathway that PITX3 takes and its exact involvement in the development of the lens. Their results proved that deficiency in MIP and Aquaporin indeed affects normal development of the lens, and it is indeed related to deficiency in PITX3. However, there is still more research needed to understand PITX3 and the genes it interacts with, and their effect in ocular development.

|
[[File:Mip1-expression-in-pitx3.jpg|thumbnail|250px|'''Analysis of mip1 expression in pitx3-mo and control embryos via in situ hybridization and RT-PCR''']]
|}

-----------

<pubmed>22496813</pubmed>

This research <ref name="PMID22496813"><pubmed>22496813</pubmed></ref> studied c-Jun N-terminal Kinase (JNK) activation in the retina of newborn rats

[[File:JNK1.png]]

<pubmed>20544023</pubmed>

<pubmed>20459797</pubmed>

[http://www.advancedcell.com/patients/clinical-trial-information/ Advanced Cell Technology]- A biotechnology company which is currently running two clinical trials that utilise human embryonic stem cell derived retinal pigmented epithelial cells. These trials are examining the possibility of using these cells to treat stargardt's macular dystrophy and dry age-related macular degeneration<ref><pubmed>22281388</pubmed></ref>.

----

===LRP5 is required for vascular development in deeper layers of the retina===

<pubmed>20652025</pubmed>

{| width=800px
|-
|
The lipoprotein receptor-related protein 5 (LRP5) has a significant function in the development of retinal vasculature.<ref name="PMID20652025"><pubmed>20652025</pubmed></ref> Research has shown that mutations of the LRP5 causes loss of function, due to incomplete development of retinal vessel network, in both humans and mice. The authors investigated how mutations occur in the LRP5, which leads to abnormal development of the retinal vasculature. They have studied retinal endothelial cells in mutant mice in their study. Their results showed that in retina with mutated LRP5, endothelial cells in the retinal vasculature primarily produced cell clusters in the inner-plexiform layer instead of migrating into deeper layers of the retina to form normal retinal vasculature. The authors also discovered that there was a decrease in Slc38a5, which is a “a Müller cell-specific glutamine transporter”, in mice with mutated LRP5. Their results lead the authors to conclude that normal LRP5 is very important in the development of normal retinal vasculature due to their role in causing migration of retinal endothelial cells in the deeper layers of the retina. LRP5 is also important for retinal interneurons and Müller cells to function correctly.

|
[[File:Retina-cell-clusters.JPG|350px|thumbnail|'''Endothelial cells form thick clusters in the LRP5 mutant retina''']]
|}

-----------------

==Useful Links==

{{External Links}}

[http://www.youtube.com/watch?v=Xme8PA6xv-M Visualisation of eye development in the embryo]

[http://www.embryo.chronolab.com/sense.htm Embryonic Development of the eye]

==Glossary==

'''Accommodation''' - changing the focal length of the lens in order to focus on an object.

'''Downstream genes''' - genes that are activated by other "upstream genes".

'''Ectoderm''' - outermost layer of germ cells in an early embryo.

'''Endoderm''' - innermost layer of germ cells in an early embryo.

'''Glial cells''' - non-neuronal cells that provide structure and protection to neurons as well as producing myelin.

'''Inductive signaling''' - a process whereby the secretion of factors from one cell or tissue triggers a response in another.

'''Lens vesicle''' - the cavity of invaginated ectoderm from the optic placode that will form the lens.

'''Macula''' - a highly pigmented, oval-shaped area located near the centre of the retina. Important for visual acuity.

'''Mesenchyme''' - undifferentiated, loose connective tissue.

'''Mesoderm''' - middle layer of germ cells in an early embryo.

'''Mesothelium''' - the epithelial layer of the mesoderm.

'''Myelinisation''' - development of a myelin sheath around a nerve fibre.

'''Neural crest''' - a portion of the ectoderm situated next to the neural tube.

'''Neural groove''' - a large invagination on the dorsal surface of the embryo which will close off and form the neural tube.

'''Neural tube''' - hollow structure that results from the folding of the neural plate and eventually forms the central nervous system.

'''Neuroblastic layer''' - a layer of immature cells that differentiate to form either glial cells or neurons. The retina has two of these (an inner and outer).

'''Neuroectoderm''' - portion of the ectoderm that develops to form the central and peripheral nervous systems.

'''Optic chiasm''' - the point at which the optic nerves meet and cross over.

'''Optic cup''' - the structure that is formed after the optic vesicle folds in upon itself. This will form the retina.

'''Optic globe''' - a term that refers to the optic cup, lens vesicle and surrounding mesenchyme collectively.

'''Optic placode''' - area of thickened ectoderm that gives rise to the lens of the eye.

'''Optic stalk''' - a long, narrow cavity that will produce the optic nerve.

'''Optic vesicle''' - a cavity that buds off from the neural tube and gives rise to the optic cup.

'''Upstream genes''' - genes that activate one or more other "downstream genes".

'''Vascularise''' - to invade with blood vessels.

==Image Gallery==
<gallery>
Image:Eye_diagram_bandw.jpg‎ | Basic structure of the human eye.
Image:Stage14 sem2b-limb.jpg | A Stage 14 embryo showing the location of an otic placode.
Image:Stage 13 image 060.jpg | A cross section showing the organisation of the developing brain, the optic vesicle and the lens (optic) placode.
Image:Formation of the optic vesicle 1.jpg | Early formation of the optic vesicle from the neural groove.
Image:Formation of the optic vesicle 2.jpg | The optic vesicle at a later stage, showing the optic stalk.
Image:Formation of the optic nerve and chiasm 1.jpg | A recognisable brain and eye structure in later development.
Image:Formation of the optic cup 1.jpg | Mechanism of optic cup formation.
Image:Formation of the optic cup 2.jpg | Layers of the optic cup in retina development.
Image:Formation of the retina 1.jpg | Cross-section of the primitive retina showing cell types and layers.
Image:Formation of the retina 2.jpg | Cross-section of a developed retina showing cell types and layers.
Image:Formation of the lens 1.jpg | The importance of the optic cup in lens differentiation.
Image:Formation of the lens 2.jpg | The lens placode separates from the ectoderm and migrates into the mesoderm forming the lens vesicle.
Image:Formation of the choroid and sclera 1.jpg | The choroid and sclera derives from mesenchyme surrounding the optic cup.
Image:Formation of the eyelid 1.jpg | Small grooves in the ectoderm of the head - the precursors to an eyelid.
Image:Formation of the eyelid 2.jpg | The eye at an advanced stage of embryonic development. Note however, that the eyelids remain fused until much later.

</gallery>

==References==
<references/>

----

--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

----

{{2012Projects}}

2012 Group Project 1

2012-10-02T13:23:27Z

Z3254758: /* Aqueous Chambers */

[[File:Eye_collage_2.jpg|right|830px]]

=Vision Development=

==Introduction==

Eyes are an important sensory organ shared across many different species and allow organisms to gather useful visual information from their environment. The visual system uses light from the environment and processes this information in the brain for visual perception. The visual system is complex, and is made up of various structures that work together to form vision. Each of the structures in the eye have specific tasks which contribute to the visual system. Knowledge of how the eye develops extends as far back as Aristotle more than 2000 years ago, and current knowledge shows that most of the crucial events of eye development occur in the embryological stage. The eye is an interesting model for studying the development of tissues in organisms, as it consists of cells from several parts of the embryo including the head ectoderm, neural ectoderm and mesoderm. From its many origins the cells come together and differentiate to produce the complex organ that is the eye. During this period there are many examples of inductive signaling, as the tissues coordinate their development throughout this elegant process.

The main anatomical structures of the eye are as follows:
{|
|
* Cornea

* Sclera

* Choroid

* Iris

* Ciliary body

* Lens

* Anterior chamber

* Posterior chamber

* Retina

* Optic nerve

|[[File:eye_diagram_bandw.jpg|right|250px|thumb|Basic structure of the human eye.]]
|}
[[File:Eyediagramcolour1.JPG|550px]]

==Research History==

=== '''Brief Timeline of Historical Developments on the Eye and its Embryology''' ===

{| width=800px
|-bgcolor="CEDFF2"
| width=100px|'''Time'''
| width=700px|'''Discovery'''

|-bgcolor="F5FAFF"
| '''Ancient Egyptians'''
| First to document cataracts. It is described as being 'the white disease of the eye' or 'darkening of the pupil.' <ref>Edwards, D.D. (1996). Ophthalmology before Hippocrates. In the History of Ophthalmology, ed. D.M. Albert and D.D. Edwards. Cambridge, Mass.: Blackwell Science.</ref> The Egyptians had some knowledge of the eye, however it is not known how much of the anatomy of the eye was known in their era.

|-bgcolor="CEDFF2"
| '''535 BC'''

|
Ancient Greek philosopher Alcmaeon conducted dissection of humans for the first time in recorded history. This included dissection of the eye. However, not much is known about which anatomical features he discovered. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17.">Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17.</ref>

|-bgcolor="F5FAFF"
| '''384- 322 BC'''

| [[File:Aristotle-eye.jpg|200px|thumbnail|The eye according to Aristotle.<ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "> Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau </ref> Note the lens is missing, and there are three vessels drawn that was believed to transport fluid to and from the eye.<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
]]
Aristotle performed dissections of animal embryos.<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

When Aristotle described the embryo of a ten day old chicken, he wrote "The eyes about this time, if taken out, are larger than beans and black; if their skin is removed the fluid inside is white and cold, shining brightly in the light, but nothing solid." <ref name="Magnus, H. (1998). Ophthalmology of the ancients. In J. Hirschberg (Ed.), The History of Ophthalmology: The monographs, Vol. 4, Part 1 (F.C. Blodi, Trans.) Bonn: Wayenborgh.">Magnus, H. (1998). Ophthalmology of the ancients. In J. Hirschberg (Ed.), The History of Ophthalmology: The monographs, Vol. 4, Part 1 (F.C. Blodi, Trans.) Bonn: Wayenborgh.</ref>

Aristotle believed that the eyes started forming during early embryogenesis, however, he also believed that the eyes are the last organs to form completely, and he incorrectly thought that the eyes shrink in later embryonic development. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press.">Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press.</ref> .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"

| '''340 BC'''

| Lens is thought to have been discovered by Hippocrates, due to his descriptions of the contents of the internal eye There has been studies in chick development later on by followers of Hippocrates. They claimed that eyes were visible in early embryogenesis. .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
|-bgcolor="F5FAFF"
|'''25 BC - 50 AD'''

| [[File:Celsus-eye.jpg|150px|thumb|The eye according to Celsus. <ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "/>
Note the lens is placed in the centre of the eye, in the vitreous.<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> ]]

Aulus Cornelius Celsus wrote a Roman medical text called 'De Medicina' in which he wrote that the lens was the part of the eye from which vision originated. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.">Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.</ref> Celsus also incorrectly drew the lens in the center of the globe in his diagram of the eye. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

|-bgcolor="CEDFF2"
| '''23-79 AD '''
|
Pliny the Elder said that the eye is the last of the organs to develop in the womb <ref name="Magnus, H. (1998). Ophthalmology of the ancients. In J. Hirschberg (Ed.), The History of Ophthalmology: The monographs, Vol. 4, Part 1 (F.C. Blodi, Trans.) Bonn: Wayenborgh."/>
|-bgcolor="F5FAFF"
| '''98-117 AD'''

| [[File:Rufus-eye.jpg|150px|thumb|The eye according to Rufus of Ephesus. <ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "/>
Note the lens is placed in the correct position, behind the iris of the eye <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> ]]

Rufus of Ephesus identified the lens as being located in the anterior part of the eye, close to the pupil. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

His diagram illustrates that he knew the correct position of the lens as being directly behind the iris, in the anterior part of the eye, and not in the centre as was previously depicted by others before him.

|-bgcolor="CEDFF2"
| '''130-200 AD'''

| [[File:Galen-eye1.jpg|150px|thumb|The eye according to Galen. <ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "/> ]]

Claudius Galen practised medicine in Rome. He wrote:

"1. Within the eye the principal orgran of sensation is the crystalline lens.

2. The sensation potential comes from the brain and is conducted via the optic nerves.

3. All other parts of the eyeball are supporting structures." <ref> Hirschberge, J. (1982). Antiquity, Vol. X in the History of Ophthalmology (F.C. Blodi, Trans.) Bonn: Wayenborgh. pp. 280 </ref>

Galen thought that the lens was produced from the vitreous. He also believed that the retina’s function was to give nourishment to the lens and vitreous, and to carry visual information to the brain from the lens. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

|-bgcolor="F5FAFF"

| '''1514-1564'''

| Andreas Vesalius published his anatomy book "De Humani Corporis Fabrica in 1543. He had the misconception that the lens was located in the centre of the eyeball. .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> He also wrote that the lens functioned "like a convex lens made of glass" <ref name="Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.">Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.</ref> pp. 48
|-bgcolor="CEDFF2"
| '''1535-1606'''

| Georg Bartisch correctly drew a diagram of the lens placed behind the iris in his book 'Ophthalmodouleia: das ist Augendienst'. <ref name="Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>
|-bgcolor="F5FAFF"

| '''1537-1619'''

| Fallopio Hieronymus Fabricius ab Aquapendente studied anatomy and embryology. He studied chicken embryos, and thought that chalazae (which comes from egg white) gives rise to the eyes. He also drew the lens directly behind the iris in a diagram in is book 'Tractatus de Oculo Visuque Organo. <ref name="Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

|-bgcolor="CEDFF2"
| '''1583'''

| Felix Platter published his book 'De corporis Humani Structura et Usu, after he performed dissections of human bodies. He believed that the retina is the primary visual organ in the eye. .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="F5FAFF"
| '''1619'''
| Scheiner is given credit to be the first person to correctly draw the diagram of the anatomy of the eye. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
|-bgcolor="CEDFF2"
| '''1672'''
| Marcello Malpighi described the embryonic development of the chicken. He drew many detailed diagrams of the chick eye. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1665'''
| Nicolaus Steno identified the choroid fissure in his study of a developing embryo of a chicken. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="CEDFF2"
| '''1754'''

| Albrecht von Haller studied the embryology of the eye. With help from his student Johann Gottfried Zinn, he contributed to the understanding of the development of the ciliary body, ciliary zonule, and their relationship with the lens and vitreous. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1817'''

| Christian Pander discovered the three embryonic germ layers, which he wrote about in his book. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/> Pander was the first to think of 'the optic vesicles as lateral evaginations' of the 'prosencephalon'; however, he was incorrect about the details regarding how 'the eye develops from these evaginations'. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="CEDFF2"
| '''1828-1837'''

| Karl Ernst von Baer studied embryology. He discovered that the optic vesicles were 'outgrowths of the embryonic forebrain' <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> which he believed was caused by pressure from fluids in the central nervous system. Von Baer also believed that the optic vesicle opens to form the pupil, and that fluid in the optic vesicle coagulates to form the vitreous body and lens. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1830'''

| Emil Huschke discovered that the lens forms from the invagination of the surface ectoderm. He concluded that the lens hence does not form ‘from the fluid of the optic vesicle’ <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> as previously thought.
|-bgcolor="CEDFF2"
| '''1832'''

| Emil Huschke wrote in his manuscript ‘Ueber die erste Entwinkenlung des Auges und die damit zusammenhängende Cyklopie’ that the lens capsule forms from the outer surface ectoderm, which detaches and moves back inward, which is later enclosed again by several membranes, such as by the cornea. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

Huschke also described how the optic cup and choroid fissure forms. He discovered that the optic vesicles are produced from the two-layered optic cup. However, he incorrectly described the destiny of the ‘individual optic cup layers’. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

|-bgcolor="F5FAFF"
| '''1838'''
| Matthias Jakob Schleiden and Theodor Schwann formulated the ‘cell theory’: “All living things are formed from cells, the cell is the smallest unit of life, and cells arise from pre-existing cells.” <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
|-bgcolor="CEDFF2"
| '''1839'''

| Theodor Schwann contributed a better understanding of the development of the lens through studying the foetus of a pig, which he wrote about in his book ‘Mikroskopische Untersuchungen Über Die Uebereinstimmung in Der Struktur Und Dem Wachsthum Der Thiere Und Pflanzen’. He wrote that the lens is made of ‘concentric layers’ of fibres which proceeds from an anterior to posterior direction. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1842'''
| Robert Remak gave the current names to the three embryonic germ layers: ectoderm, mesoderm and endoderm. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"
| '''1843'''
| Wilhelm Werneck published his book ‘Beiträge zur Gewebelehre des Kristallkörpers’. He wrote that the contents inside of the lens is not made of fluids, as was previously believed. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/> Werneck also discovered that the fibers of the lens continues to grow from the outside to the centre during embryogenesis. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

|-bgcolor="F5FAFF"
| '''1855'''

| Robert Remak wrote his book ‘Untersuchungen über die Entwickelung der Wirbelthiere’. He wrote about what he discovered in his studies of the development of the eye in the embryos of chickens, frogs, and rabbits. He wrote very descriptively about the embryology of lens formation, amongst other topics. He discovered that the ectoderm gives rise to the lens placode. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

|-bgcolor="CEDFF2"
| '''1858'''
| Henry Gray published his book 'Anatomy, Descriptive and Surgical'. He had also previously studied the embryonic development of the optic nerve and retina of chickens.
|-bgcolor="F5FAFF"
| '''1877'''
| Paul Leonhard Kessler wrote about the embryonic development of the lens in mice in his book ‘Zur Entwickelung des Auges der Wirbelthiere. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"
| '''1891'''
| Vincenzo Colucci studied newts and discovered their ability to regenerate the lens.<ref> Tsonis, P. A. (2001). Regeneration of the Vertebrate Lens and Other Eye Structures. eLS. (Online Publication). DOI: 10.1038/npg.els.0001102 </ref>
|-bgcolor="F5FAFF"
| '''1892'''
| Dr. Oscar Hertwig published his book ‘Text-Book of the Embryology of Man and Mammals. <ref> Hertwig, O. Text-book of the embryology of man and mammals. S. Sonnenschein 1901. (Translated from the 3d German ed. by Edward L. Mark.) </ref> It contains a very detailed description of the development of the eye, according to the findings at that time. [http://embryology.med.unsw.edu.au/embryology/index.php?title=Book_-_Text-Book_of_the_Embryology_of_Man_and_Mammals_16-2#The_Development_of_the_Eye]
|-bgcolor="CEDFF2"
| '''1895'''
| Gustav Wolff also independently studied newts and discovered their ability to regenerate the lens. .<ref> Tsonis, P. A. (2001). Regeneration of the Vertebrate Lens and Other Eye Structures. eLS. (Online Publication). DOI: 10.1038/npg.els.0001102 </ref>

|-bgcolor="F5FAFF"

| '''1900'''
| Carl Rabl published his book ‘Uber den Bau und die Entwicklung der Linse’. He wrote about the development of the lens in mammals, fish, birds, reptiles, and amphibians. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"
| '''1901'''
| Hans Spemann published his findings from his experimental studies about the formation of the lens in the frog. He found that the optic cup needed to be in contact with the ectoderm for normal development of the eye. <ref> Spemann, H. (1901). Über Correlationen in der Entwicklung des Auges. Verhand. Anat. Ges. 15: 61-79. </ref> <ref> Saha, M. (1991). Spemann seen through a lens. In Gilbert, S. F. (ed.). A Conceptual History of Modern Embryology. Plenum Press, NY. pp. 91-108.</ref>
|-bgcolor="F5FAFF"
| '''1906'''
| Brown ‘s book “The Embryology Anatomy and Histology of the Eye” was published. It contained detailed descriptions of the embryonic development of the eye according to the knowledge current at that time, mainly based on observations from embryos of rabbits and chickens. <ref> Brown, E.J. (1906). The Embryology Anatomy and Histology of the Eye. Chicago: Hazlitt & Walker. 1906 </ref>

|-bgcolor="CEDFF2"
| '''1907'''

| John Clement Heisler published his book ‘A Text-book of embryology’. It contains a chapter detailing the embryonic development of the eye, according to the knowledge current at that time. The book’s copyright has expired, so it can be viewed free online: [http://archive.org/details/atextbookembryo01heisgoog]

Julius Kollman also published his book 'Atlas of the Development of Man'. It contained very detailed description and illustrations showing the embryonic development of the human according to the knowledge current at that time. His illustrations were reused by many others after his time and built upon for further refined understanding of the embryology of the human.

Here are examples of Julius Kollman's excellent illustrations showing eye development in various stages:

'''Formation of Primary Optic Vesicle:'''
<gallery>
File:Kollmann691.jpg|The blue part at the bottom is the endoderm. The pink middle layer is the mesoderm. The top yellow layer is the ectoderm. The fold labelled as 'augenfeld' is the place where the optic vesicle will form.
File:Kollmann692.jpg|The eye area (augenfeld) is a bowl shaped bulge still located on the side walls.
File:Kollmann693.jpg| The neural tube is shown after removal of all of the ectoderm and ventral organs, such as heart, gut tube, etc. The primary optic vesicle forms a slightly flattened hollow protrusion on the forebrain.
File:Kollmann694.jpg|The lateral surface of the primary optic vesicle is slightly depressed, showing the first sign of the emergence of the secondary optic vesicle
</gallery>

'''Development of Lens:'''

<gallery>
File:Kollmann695.jpg|The bulging lateral wall of the primary optic vesicle is covered by a fairly well demarcated lens plate, a direct continuation of the ectoderm. Between the optic vesicle and the lens pit are some flattened spindle-shaped cells. In the adjoining mesoderm are cross-sections of capillaries.
File:Kollmann697.jpg|The lens still hangs together with the ectoderm. The primary eye vesicle is indented with respect to the lens. Between the lens and the lateral plate of the optic vesicle is a narrow space, which allows area to further develop later.
File:Kollmann698.jpg|4th Week of development. The internal organisation shows the secondary optic vesicle. A: The rear wall of lens is noticeable and is enveloped by mesoderm. B: The edges of the lens pit is already grown and the lens vesicles are formed, which is still related to the remaining ectoderm.
File:Kollmann699.jpg|The lens has now cut off from the ectoderm, but is still very superficial. Between it and the lateral lamina of the optic cup, there is a considerable space. The eye stalk has become longer and is enclosed together with the optic cup and lens of the mesoderm. The cornea, sclera and choroid make gradual development.
</gallery>

|-bgcolor="F5FAFF"

| '''1921'''
| Bailey and Miller published their textbook “Text-Book of Embryology “. <ref> Bailey, F.R. and Miller, A.M. (1921). Text-Book of Embryology. New York: William Wood and Co. (Note- This book is only at an early edited stage)</ref> It contains detailed description of the development of the embryonic eye according to the knowledge current at that time. [http://embryology.med.unsw.edu.au/embryology/index.php?title=Book_-_Text-Book_of_Embryology_18]

|-bgcolor="CEDFF2"
| '''1925'''

| Mann published his research article, in which he gives a detailed account of the development of the human iris. He divided the development of the iris into four stages: weeks 4-7 (before the ectodermal iris forms or before the anterior chamber forms); weeks 7-11 (anterior chamber appears, and mesodermal iris forms); weeks 11-12 (ectodermal iris forms); 3-8 months (muscles of the pupil forms from ectodermal iris, and the central portion of the mesodermal iris atrophies to make the pupil clear). <ref name="PMID18168466"><pubmed>18168466</pubmed></ref>
O Leser also published an article detailing the development of extraocular muscles in mammals he studied. <ref name="PMID18168498"><pubmed>18168498</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1939'''
| Holtfreter <ref> Holtfreter, J. (1939). Gewebeaffinitat, ein Mittel der embryonalen
Formbildung. Arch. Exp. Zellforsch. 23, 169-209. </ref> studied amphibians and observed that that the development of the eye stops at the ‘optic vesicle stage’ if there is no contact ‘with the epidermis and neural crest driven mesenchyme’. <ref name=”PMID11023863”><pubmed>11023863</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1955'''
| Barber published his book ‘Embryology of the human eye’. <ref> Barber AN: Embryology of the human eye. St. Louis. CV Mosby 1955</ref> In contains detailed descriptions of the embryological development of the human eye according to the knowledge current at that time. It contains many photographs of the eye at different stages of development.

|-bgcolor="F5FAFF"
| '''1957'''
| Coulombre studied a chicken embryo to find the role of intraocular pressure in the development of the chick’s eye, especially in regards to its control of the size of the eye structures. <ref name="PMID13469954"><pubmed>13469954</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1958'''
| Coulombre studied the development of the cornea and how it develops its transparency. <ref name="PMID13563560"><pubmed>13563560</pubmed></ref> He also studied the development of corneal curvature. <ref name="PMID 13519969"><pubmed> 13519969</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1962'''
| Coulombre studied the development of the conjunctival papillae and scleral ossicles. <ref name="PMID 14023393"><pubmed> 14023393</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1963'''
| Coulombre studied the development of lens fibers and their orientation. <ref name="PMID14077035"><pubmed>14077035</pubmed></ref> He also studied the development of pigmented epithelium. <ref name="PMID14023394"><pubmed>14023394</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1964'''

| Coulombre further studied the development of the lens to determine the role of the lens in eye growth. <ref name="PMID14189921"><pubmed>14189921</pubmed></ref> He also studied the role of thyroid in the development of the cornea and the development of corneal transparency. <ref name="PMID14211912"><pubmed>14211912</pubmed></ref> Mann also published his work called ‘The development of the human eye’, which contains detailed description of the embryonic development of the eye according to current knowledge at that time. <ref> Mann I. The development of the human eye. New York: Grune and Stratton 1964</ref>

|-bgcolor="CEDFF2"
| '''1965'''
| Coulombre published his findings regarding the regeneration of the neural retina from pigmented epithelium in the embryo of chickens. <ref name="PMID5833111"><pubmed>5833111</pubmed></ref> Smelser also published his findings on the embryological development and morphology of the lens. <ref name="PMID14340157"><pubmed>14340157</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1966'''

| Formation of the face and orbit occurs from the differentiation of neural crest cells. <ref name="PMID5969670"><pubmed>5969670</pubmed></ref> O’Rahilly also published findings of the development of the eye in the early stages of human embryos. <ref> O'Rahilly, R. 1966 The early development of the eye in staged human embryos. Contr. Embry. Carnegie Inst., Wash., 38: 1–42</ref>

|-bgcolor="CEDFF2"
| '''1968'''
| Findings of the postnatal development of the retina of rats was published. <ref name="PMID5640327"><pubmed>5640327</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1969'''

| Mann again published his work called ‘The development of the human eye’. He stated that that the lens in humans forms completely from the ectoderm. <ref name=”Mann I. The Development of the Human Eye. New York, USA: Grune & Stratton, Inc; 1969”> Mann I. The Development of the Human Eye. New York, USA: Grune & Stratton, Inc; 1969</ref> Coulombre also studied the development of the lens, and took note of its size, shape and orientation throughout its developmental stages. <ref name="PMID 5772716"><pubmed> 5772716</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1970'''
| Coulombre again further studied the regeneration of the neural retina from pigmented epithelium of embryos of chickens. <ref name="PMID 5472476"><pubmed> 5472476</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1971'''

| Coulombre further studied the development of the lens. This time he focused on analysing the histological mechanisms in the reconstitution of the lens from implanted lens epithelium. <ref name="PMID 4925671"><pubmed> 4925671</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1973'''
| A research article was published, detailing the embryonic development of the retina of humans. <ref name="PMID 6650859"><pubmed> 6650859</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1976'''

| Geeraets published his observations of the closure of the embryonic optic fissure in golden hamsters, using the electron microscope. <ref name="PMID 1266776"><pubmed> 1266776</pubmed></ref> Kornneef also published an article based on his studies of the development of connective tissue in the human orbit. <ref name="PMID 1020699"><pubmed> 1020699</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1981'''
| A research article was published detailing how myelin forms in the optic nerve of humans. <ref name="PMID 7224936"><pubmed> 7224936</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1983'''
| O’Rahilly’s further research developments was published, reporting the timing and sequence of events in the development of the embryonic human eye. <ref name="PMID 6650859"><pubmed> 6650859</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1990'''

| Van Driell et al. <ref>Driell, D. Van; Provis, J.M.; Billson, F.A.: Early differentiation of ganglion, amacrine, bipolar and Muller cells in the developing fovea of the human retina. J. Comp. Neurol. 291: 203-219.</ref> studied the manner in which amacrine, bipolar, retinal ganglion cells, and Muller cells differentiate in the developing fovea of the retina of a 15-week old human foetus. <ref name="PMID1628748"><pubmed>1628748</pubmed></ref> Tripathy also published an article providing evidence that the lacrimal glands in humans originates from the neuroectoderm. <ref name="PMID2406219"><pubmed>2406219</pubmed></ref>

|}

==Development, Structure and Function of Ocular Components==

The eye itself is formed from several components; notably the optic placode of the head ectoderm, the optic vesicle from the neural tube, and mesenchyme from the mesoderm and neural crest cells. The optic placode contributes the lens to the eye, the optic vesicle gives rise to layers of the retina, while the mesenchyme will produce the ciliary body, iris, choroid and sclera.<ref>http://www.vetmed.vt.edu/education/curriculum/vm8054/eye/EMBYEYE.HTM</ref> Cells from the neural tube will also produce the optic nerve, which receives nerve impulses from the retina of the eye. Eyes initially form as laterally paired structures and migrate medially in the human embryo. In other animals such as birds and lizards, the eyes do not migrate and develop laterally on the head. The optic placodes become prominent on the surface of the embryo at approximately Stage 14 of development.

[[File:Stage14 sem2b-limb.jpg|200px|thumb|left|A Stage 14 embryo showing the location of an otic placode.<ref name="http://embryology.med.unsw.edu.au/embryology/index.php?title=ANAT2341_Lab_6_-_Early_Embryo">http://embryology.med.unsw.edu.au/embryology/index.php?title=ANAT2341_Lab_6_-_Early_Embryo</ref>]] [[File:Stage 13 image 060.jpg|400px|thumb|center|A cross section showing the organisation of the developing brain, the optic vesicle and the lens (optic) placode.<ref name="http://embryology.med.unsw.edu.au/embryology/index.php?title=ANAT2341_Lab_6_-_Early_Embryo"/>]]

===Optic Nerve===

The optic nerve consists of nerve fibres that transmit information from the retinal photoreceptor cells to the brain. The optic nerve is formed from the optic stalk, which develops as the optic vesicle migrates from its origin in the neural tube to its destination - the surface ectoderm - where it will fuse with the optic placode (also known as the lens placode, which will contribute the lens to the eye).<ref name="PMID11687490"><pubmed>11687490</pubmed></ref>

[[File:Formation of the optic vesicle 1.jpg|400px|thumb|left|Fig. 1: Early formation of the optic vesicle from the neural groove.]] [[File:Formation of the optic vesicle 2.jpg|400px|thumb|center|Fig. 2: The optic vesicle at a later stage, showing the optic stalk.]]

As can be seen in Figure 1 above, the optic vesicle forms from the neural tube. However, note that the neural tube has not yet closed, and is still the neural groove at this point. Figure 2 then shows the optic vesicle at slightly later stage in the same simplified cross-section of the embryo, as it migrates from the neural tube to the surface ectoderm. Note the presence of the optic stalk which links the optic vesicle to the neural tube. Later in development, this primitive structure will become the optic nerve, which will link the eye to the brain.

The nerve fibres themselves will initially originate from the retinal ganglion cells in the eye during week 6.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008">Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008</ref> After two weeks, these fibers will have grown along the inner wall of the optic stalk and have reached the brain. They grow both in length and width, with the nerve fibres filling the hollow optic stalk to form the solid optic nerve. More than one million nerve fibers will eventually make up the optic nerve, along with glial cells which arise from the inner wall of the optic stalk itself.<ref><pubmed>1451666</pubmed></ref> Myelinisation of the optic nerve begins much later in development at around 7 months, beginning at the optic chiasm and moving towards the eye.<ref><pubmed>7224936</pubmed></ref> The optic chiasm forms just before the nerves reach the brain, and is where half the nerve fibres from each eye will cross over to the opposite side of the brain. This is demonstrated in Figure 3. Note the crossing over of the optic nerves just before they enter the brain, at the optic chiasm. This organisation is now much more familiar, with the eyes near the ectoderm and the optic nerve leading through the mesoderm to the brain buried deep in the embryo.

[[File:Formation of the optic nerve and chiasm 1.jpg|400px|thumb|center|Fig. 3: A recognisable brain and eye structure in later development.]]

===Retina===

The retinal component of the eye is formed when the optic vesicle folds in upon itself, forming the optic cup (see Figure 4). In doing so it creates two layers - an inner wall and an outer wall of the optic cup (Figure 5). These two layers of the optic cup will give rise to the two layers of the retina - the inner neural retina, and the outer pigmented epithelium.<ref name="PMID11687490"/> Note the existence of the space between the two layers of the retina. This is known as the intraretinal space and disappears by the 7th week of development, however the two layers never completely fuse and can become separated as a result of physical trauma to the head - leading to a detached retina and loss of vision.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/>

The inner wall of the optic cup, which will give rise to the neural retina, consists of a layer of pseudostratified cells (see Figure 6) that later differentiate into rod, cone, bipolar, ganglion, horizontal, amacrine and glial cells of the retina (Figure 7).<ref name="PMID18168748"><pubmed>18168748</pubmed></ref> The outer wall of the optic cup consists of a layer of cuboidal cells that contain melanin - the light absorbing pigment. The function of this layer is to absorb light and prevent internal reflection of light within the eye, which would impair our ability to form distinct images. Interestingly, in some animals such as cats, this layer actually reflects light intentionally to increase the amount of light available to the eye in low-light conditions. This is why cats seem to have eyes that glow in the dark.<ref>http://dialspace.dial.pipex.com/agarman/bco/fact4.htm</ref>

[[File:Formation of the optic cup 1.jpg|400px|thumb|left|Fig. 4: Mechanism of optic cup formation.]] [[File:Formation of the optic cup 2.jpg|400px|thumb|center|Fig. 5: Layers of the optic cup in retina development.]]

The inner wall itself is divided into two components - the inner neuroblastic layer and the outer neuroblastic layer (see Figure 6). The outer neuroblastic layer forms the rod and cone cells while the inner neuroblastic layer forms the remaining cell types found in the retina - the bipolar, ganglion, horizontal, amacrine and glial cells (Figure 7).<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/> The organisation of the retina is interesting in that incoming light passes through several layers of these neural retina cells before it is detected by rod and cone cells at the back of the retina, and then nerve signals are passed back through the layers of neural retina cells that the light just passed through moments before - a seemingly strange design that the eye does not share with man-made light-capturing devices such as a camera (imagine putting the wires in front of the image sensor!).

Differentiation of the neuroblastic layers into neural retina cells occurs in a pattern both within the layers and across the retina. Cells differentiate from the inner neuroblastic layer to the outer neuroblastic layer, and differentiate from the central retina to the peripheral retina.<ref name="PMID18168748"/> The macula is first identifiable in week 22 when ganglion cells start to form multiple rows, and the primitive fovea begins to form at approximately the same time as a depression in the macula.<ref><pubmed>6462623</pubmed></ref> It is not until 15-45 months after birth that this area becomes exclusively populated by cone cells and becomes the fovea centralis - the area of the retina with the highest visual acuity.

[[File:Formation of the retina 1.jpg|400px|thumb|left|Fig. 6: Cross-section of the primitive retina showing cell types and layers.]] [[File:Formation of the retina 2.jpg|400px|thumb|center|Fig. 7:Cross-section of a developed retina showing cell types and layers.]]

===Ciliary Body===

The ciliary body consists of ciliary processes and three portions of fibres that constitute the ciliary muscles. It functions to maintain normal eye physiology as well as playing a direct role in accommodation.

During development, the ciliary processes form slightly posterior to the iris, developing from part of the anterior rim of the optic cup. It is thought that the folded structure of the ciliary processes is brought about by intraocular pressure and specific signalling pathways.<ref name="PMID16959249"><pubmed>16959249</pubmed></ref> While the ciliary muscles and the endothelial cells of the ciliary blood vessels are chiefly formed by mesenchymal cells<ref><pubmed>16249499</pubmed></ref>, the neural crest and neuroectoderm also contribute to their development.<ref><pubmed>12127103</pubmed></ref> The normal development of the ciliary body is dependent on the correct expression of bone morphogenetic protein (BMP)-4, which is a member of the transforming growth factor-β superfamily.<ref><pubmed>1222340</pubmed></ref> Napier and Kidson (2007) summarised numerous genes that have been associated with ciliary body development, however their direct roles have not been well documented.<ref name="PMID16959249"/>

===Iris===

The iris is a thin layer that develops at the end of the third month of development and is derived from the anterior rim of the optic cup. The stroma of the iris develops from cells of neural crest cell origin.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/> The muscles that are responsible for the dilation and constriction of the pupil (dilator pupillae and sphincter pupillae muscles) form from the neuroectoderm of the optic cup. These cells are initially epithelial cells that then transform into smooth muscle cells. <ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"></ref>. The invagination of the optic vesicle which creates the optic cup, also causes the formation of the optic cup lip. This is the region of the where the epithelium doubles back, separating the outer pigmented layer and the inner nonpigmented layer. This is the edge of the iris that borders on the pupil<ref><pubmed> Retinal and anterior eye compartments derive from a common progenitor pool in the avian optic cup</pubmed></ref>.

The final colour of the iris is not evident until the postnatal period. It is determined by a number of genes including IRF4, SLC24A4 and MATP<ref><pubmed>19710684</pubmed></ref>. Other features such as crypt frequency, furrow contractions, presence of peripupillary pigmented ring, and number of nevi also become evident during development<ref><pubmed>21835309</pubmed></ref>.

Mutations in Pax6 have been shown to cause partial or complete loss of the iris <ref><pubmed>12386935</pubmed></ref>.

===Cornea===

The cornea is the transparent, avascular, most anterior portion of the eye. It is responsible for conducting light into the eye and focusing it on to the retina, as well as maintaining the rigidity of the eyeball. It consists of 5 layers- the epithelium, Bowman’s layer, stroma, Descemet’s membrane and the endothelium.

The epithelium and endothelium of the cornea first appear during the 5th week of gestation. The epithelium of the external surface of the cornea is derived from surface ectoderm, while the mesenchyme is derived from the mesoderm<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"/>. The endothelium is a two-cell cuboidal layer which is made up of differentiated neural crest cells that were initially from the optic cup. By week 8 the endothelial cells begin to secrete a basement membrance which later forms Descemet’s membrane<ref><pubmed>6511224</pubmed></ref>. At approximately 16 weeks gestation the Bowman’s membrane begins to form from the thickening of the stroma that is located under the corneal epithelium<ref>Riordan-Eva P, Whitcher JP. Vaughn and Asbury's General Ophthalmology, Lange Medical Books/McGraw Hill. 2004:25–27</ref>. During the third month glycosaminoglycans secreted by fibroblasts form the ground substance of the cornea, with collagen fibrils and keratan sulphate also appearing around this time. Shortly after this tight junctions form between the endothelial cells<ref><pubmed>19481138</pubmed></ref>. Fibroblast growth factor causes the epithelial cells to proliferate<ref><pubmed>20105280</pubmed></ref>.

Towards the end of the gestational period the cornea becomes larger due to the production of aqueous humor<ref>Yanoff M, Duker JS. Ophthalmology. Mosby; St. Louis, MO: 2004</ref>. The final transparent structure develops because hyaluronidase removes hyaluronic acid, thyroxine causes dehydration of the stroma, and the entire structure becomes avascular<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/>. Numerous genes have been implicated in the development of the cornea, these include, but are not limited to, PAX6, PITX2, FOXC1, MAF, TMEM114, SOX2, OTX2 and BMP4<ref><pubmed>18637741</pubmed></ref>.

===Lens===

The lens has its origin from the optic placode, which develops on the ectodermic surface of the embryo and migrates both medially and inwards into the embryo. The lens allows accommodation of the eye, and adjusts its thickness in order to focus on near or far objects. The study of lens development was one of the first to highlight the importance of inductive signaling in development, with Spemann's pioneering work at the start of the 20th century, finding that the absence of retinal development resulted in the absence of lens formation.<ref name="PMID11687490"/> Indeed, it has been consistently shown that the interaction of the migrating optic vesicle with the surface ectoderm of the head is vital in producing differentiation of the lens.<ref name="PMID15558475"><pubmed>15558475</pubmed></ref> The mechanism of interaction is complex but basically involves upstream genes switching on downstream genes, with the genes eventually producing specialised proteins which constitute the lens. The whole process starts with the signaling molecules from the optic cup initiating a thickening of the surface ectoderm of the head (Figure 8). It is thought that this region of specific ectoderm is responsive to the signaling molecules, as lens formation is incomplete or absent when ectoderm from the lateral portion of the embryo (i.e. non-head ectoderm) is exposed to the same inductive signaling processes.<ref name="PMID9216064"><pubmed>9216064</pubmed></ref> Pax6 has been shown to be one of the major genes required for differentiation of the lens, which in turn switches on transcriptional genes such as Sox 1, 2 and 3 among others - producing water-soluble proteins called crystallins - responsible for giving the lens its transparency and refractive properties.<ref name="PMID9609835"><pubmed>9609835</pubmed></ref>

[[File:Formation of the lens 1.jpg|400px|thumb|left|Fig. 8: The importance of the optic cup in lens differentiation.]] [[File:Formation of the lens 2.jpg|400px|thumb|center|Fig. 9: The lens placode separates from the ectoderm and migrates into the mesoderm forming the lens vesicle.]]

The lens placode invaginates from the head ectoderm and migrates into the mesoderm (Figure 9). Once this structure (now known as the lens vesicle) is in place opposite the optic cup, the combined structure is referred to as the optic globe and resembles a recognisable eye structure. The lens continues to differentiate further, as mentioned above, through the formation of crystallin proteins, which give the lens its unique properties and allows for the fine control over the degree of refraction that takes place.

===Aqueous Chambers===

There are both anterior and posterior aqueous chambers of the eye which contain aqueous humour. A space develops in the mesenchyme situated between the lens and cornea to form the anterior aqueous chamber. The mesenchyme located superficially to this chamber forms the mesothelium as well as the transparent portion of the cornea.

The posterior chamber develops from a similar space in the mesenchyme, however it is located between the iris and the lens. The anterior and posterior chambers are able to communicate with one another once the papillary membrane vanishes and the pupil is formed. This channel is known as the scleral venous sinus.<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011">Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011</ref>

Contained within the aqueous chambers is aqueous humor. The production of aqueous humor is dependant on the development of the ciliary body. It is produced in the ciliary processes and it’s production is a metabolic process driven by the delivery of oxygen and the removal of wastes via the ciliary circulation<ref><pubmed>20801226</pubmed></ref>.

===Cornea===

The cornea is the transparent, avascular, most anterior portion of the eye. It is responsible for conducting light into the eye and focusing it on to the retina, as well as maintaining the rigidity of the eyeball. It consists of 5 layers- the epithelium, Bowman’s layer, stroma, Descemet’s membrane and the endothelium.

The epithelium and endothelium of the cornea first appear during the 5th week of gestation. The epithelium of the external surface of the cornea is derived from surface ectoderm, while the mesenchyme is derived from the mesoderm<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"/>. The endothelium is a two-cell cuboidal layer which is made up of differentiated neural crest cells that were initially from the optic cup. By week 8 the endothelial cells begin to secrete a basement membrance which later forms Descemet’s membrane<ref><pubmed>6511224</pubmed></ref>. At approximately 16 weeks gestation the Bowman’s membrane begins to form from the thickening of the stroma that is located under the corneal epithelium<ref>Riordan-Eva P, Whitcher JP. Vaughn and Asbury's General Ophthalmology, Lange Medical Books/McGraw Hill. 2004:25–27</ref>. During the third month glycosaminoglycans secreted by fibroblasts form the ground substance of the cornea, with collagen fibrils and keratan sulphate also appearing around this time. Shortly after this tight junctions form between the endothelial cells<ref><pubmed>19481138</pubmed></ref>. Towards the end of the gestational period the cornea becomes larger due to the production of aqueous humor<ref>Yanoff M, Duker JS. Ophthalmology. Mosby; St. Louis, MO: 2004</ref>. The final transparent structure develops because hyaluronidase removes hyaluronic acid, thyroxine causes dehydration of the stroma, and the entire structure becomes avascular<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/>. Numerous genes have been implicated in the development of the cornea, these include, but are not limited to, PAX6, PITX2, FOXC1, MAF, TMEM114, SOX2, OTX2 and BMP4<ref><pubmed>18637741</pubmed></ref>.

===Choroid and Sclera===

The choroid and sclera are adjacent layers that surround the eye and act to vascularise and protect the eye respectively. They are formed from neural crest and mesoderm-derived mesenchyme which condenses around the optic cup and lens vesicle between weeks 5 and 7 of development to form a primitive eyeball structure known as the optic globe.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/> Blood vessels first start to appear in the choroid layer at approximately week 15, and arteries and veins can be distinguished by week 23.<ref>Development of the Choroid and Related Structures, K. Sellheyer, Eye (1990) 4, 255-261</ref> Inductive processes are thought to play a vital role during formation of the choroid and sclera; with the retinal pigmented epithelium inducing differentiation of the surrounding mesenchyme while at the same time the neural crest-derived mesenchyme contributing components to the retinal pigmented epithelium such as melanocytes.<ref name="PMID1628748"/> In addition to having functional roles themselves, the primitive choroid and sclera also contribute components to the developing ciliary body and cornea (Figure 10). In the adult eye, the choroid is continuous with the ciliary body and the sclera with the cornea.

[[File:Formation of the choroid and sclera 1.jpg|400px|thumb|center|Fig. 10: The choroid and sclera derives from mesenchyme surrounding the optic cup.]]

===Eyelids===

The eyelids are ectodermal and mesodermal in origin and are an extension of the skin which covers and protects the eye. Eyelid formation can be first noted during week 5 when small grooves develop in the surface ectoderm (Figure 11).<ref><pubmed>7364662</pubmed></ref> These small grooves deepen and extend into the mesoderm and the primitive eyelid structures grow towards one another, eventually fusing together during week 8.<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"/> It is not until week 26-28 that the eyelids will separate again. The ectoderm reflects over the developing cornea to form the conjunctival sac, a space that is filled by secretions from the lacrimal gland in order to allow smooth motions of the eyelid over the eye and also to clean the cornea and prevent accumulation of particles on the eye that may disrupt vision. By the time the eyelids separate, the eye has all its major components present (Figure 12), and further development consists mainly of growth and vascularisation.

[[File:Formation of the eyelid 1.jpg|400px|thumb|left|Fig.11: Small grooves in the ectoderm of the head - the precursors to an eyelid.]] [[File:Formation of the eyelid 2.jpg|400px|thumb|center|Fig. 12: The eye at an advanced stage of embryonic development. Note however, that the eyelids remain fused until much later.]]

===Lacrimal Glands===

Lacrimal glands initially develop from budding of the conjunctival epithelium near the superolateral portion of the eye. The mesenchymal cells that surround these buds are of neural crest origin, and the budding continues until the mature gland is formed.<ref><pubmed> 9882499</pubmed></ref> These glands are responsible for the production of tears however they do not start to function until 1-3 months after birth.

==Current Research==

*more info will be added soon!!

===GABA Maintains the Proliferation of Progenitors and Non-Pigmented Ciliary Epithelium===

<pubmed>22590629</pubmed>

{| width=800px
|-
| width=450px|
| width=350px|

|-
| GABA is an ‘inhibitory neurotransmitter’ in the central nervous system of adults. <ref name="PMID22590629"><pubmed>22590629</pubmed></ref> It is responsible for controlling proliferation of stem cells and progenitor cells. The authors of this article <ref name="PMID22590629"/> was interested to find the effects of GABA on proliferation of progenitor cells and non-pigmented ciliary epithelial cells (NPE) in the retina. Their study focused on progenitor cells and non-pigmented epithelium of the ciliary body in chickens. Non-pigmented epithelial cells in chickens arise from the neuroepithelium of the optic cup. They share similar functions as progenitors of the early retina, such as expression of Chx10 and Pax6 genes. It is not agreed upon whether epithelial cells of the ciliary body have stem cell properties. However, it has been found that these cells can be cultured and transplanted into retinas that are injured, in order to replace neurons that were previously lost. However, there is not much known about what factors regulate the proliferation of stem cells. Hence the authors were interested in finding the effects of GABA on proliferation of retinal cells. Their results showed that non-pigmented epithelial cells in chickens ‘express extrasynaptic-like GABAA receptors’ that have the ability to regulate cell proliferation. It has been found that inhibiting these ‘GABAA receptors’ also causes a decrease in proliferation of retinal progenitor cells and non-pigmented epithelial cells in 'the intact E8 retina’. <ref name="PMID22590629"/>

|
[[File:Gaba-effects-retina.JPG|thumbnail|250px|'''GABAA receptor mediated effects on retinal progenitor cell proliferation'''
]]
|}

-------------------

===The impact of visible light on the immature retina===

<pubmed>22405869</pubmed>

The authors mentioned in this article <ref name="PMID22405869"><pubmed>22405869</pubmed></ref> that they were interested in investigating the effect of light on postnatal eye development in mice, because mice are born with fused eyelids, which separate 12 days after birth. Before the eyelids separate, the retina develops in mice with very little radiation from light. It is believed that the darkness plays a role in the development of the retina in mice, which is why their eyelids are fused for 12 days after birth. Therefore the authors were interested to see what effect light would have on postnatal retinal development of mice, with special interest in retinal ganglion cells (RGC). In their experiment, they surgically opened the eyelids on the right eyes of some of the mice to expose them to visible light 12 hours per day, while they left some other mice in the dark after surgical separation of their eyelids. They also kept the left eyes of the mice naturally fused as controls in the experiment. Their results showed that early light exposure in mice causes a decrease in retinal ganglion cells because it affects cellular apoptosis in the retina. The authors also observed that early exposure to light in mice causes lumican mRna transcription to resume and to quickly increase. (Lumican normally stays silent in retina after birth).

---------

===MIP/Aquaporin 0 Represents a Direct Transcriptional Target of PITX3 in the Developing Lens===

<pubmed>21698120</pubmed>

{| width=800px
|-
|PITX3 plays a siginificant role in the development of lens in vertebrates. If there is a deficiency is PITX3, it causes a range of problems in humans such as microphthalmia, Peter’s anomaly, or isolated cataracts. Mutation of PITX3 also causes degeneration of the lens in zebrafish and mice. It is therefore important to understand what factors may affect the decrease in PITX3, as a normal level of PITX3 is needed to maintain normal eye development. The authors wanted to investigate specific genes which are affected by PITX3. Previous research has shown that MIP and Aquaporin causes defects in the lens in both mice and humans. MIP and Aquaporin are targeted by PITX3, so their imbalance is interrelated in the cause of defects in the lens. Therefore it has been previously proven that PITX3 is needed for normal development of the lens. However, there has not been much information previously known regarding the exact effect that PITX3 has, or the specific genes it targets. Since MIP and Aquaporin is common genes found in humans, mice and zebrafish, the authors <ref name="PMID21698120"><pubmed>21698120</pubmed></ref> chose to study these genes to understand the pathway that PITX3 takes and its exact involvement in the development of the lens. Their results proved that deficiency in MIP and Aquaporin indeed affects normal development of the lens, and it is indeed related to deficiency in PITX3. However, there is still more research needed to understand PITX3 and the genes it interacts with, and their effect in ocular development.

|
[[File:Mip1-expression-in-pitx3.jpg|thumbnail|250px|'''Analysis of mip1 expression in pitx3-mo and control embryos via in situ hybridization and RT-PCR''']]
|}

-----------

<pubmed>22496813</pubmed>

This research <ref name="PMID22496813"><pubmed>22496813</pubmed></ref> studied c-Jun N-terminal Kinase (JNK) activation in the retina of newborn rats

[[File:JNK1.png]]

<pubmed>20544023</pubmed>

<pubmed>20459797</pubmed>

[http://www.advancedcell.com/patients/clinical-trial-information/ Advanced Cell Technology]- A biotechnology company which is currently running two clinical trials that utilise human embryonic stem cell derived retinal pigmented epithelial cells. These trials are examining the possibility of using these cells to treat stargardt's macular dystrophy and dry age-related macular degeneration<ref><pubmed>22281388</pubmed></ref>.

----

===LRP5 is required for vascular development in deeper layers of the retina===

<pubmed>20652025</pubmed>

{| width=800px
|-
|
The lipoprotein receptor-related protein 5 (LRP5) has a significant function in the development of retinal vasculature.<ref name="PMID20652025"><pubmed>20652025</pubmed></ref> Research has shown that mutations of the LRP5 causes loss of function, due to incomplete development of retinal vessel network, in both humans and mice. The authors investigated how mutations occur in the LRP5, which leads to abnormal development of the retinal vasculature. They have studied retinal endothelial cells in mutant mice in their study. Their results showed that in retina with mutated LRP5, endothelial cells in the retinal vasculature primarily produced cell clusters in the inner-plexiform layer instead of migrating into deeper layers of the retina to form normal retinal vasculature. The authors also discovered that there was a decrease in Slc38a5, which is a “a Müller cell-specific glutamine transporter”, in mice with mutated LRP5. Their results lead the authors to conclude that normal LRP5 is very important in the development of normal retinal vasculature due to their role in causing migration of retinal endothelial cells in the deeper layers of the retina. LRP5 is also important for retinal interneurons and Müller cells to function correctly.

|
[[File:Retina-cell-clusters.JPG|350px|thumbnail|'''Endothelial cells form thick clusters in the LRP5 mutant retina''']]
|}

-----------------

==Useful Links==

{{External Links}}

[http://www.youtube.com/watch?v=Xme8PA6xv-M Visualisation of eye development in the embryo]

[http://www.embryo.chronolab.com/sense.htm Embryonic Development of the eye]

==Glossary==

'''Accommodation''' - changing the focal length of the lens in order to focus on an object.

'''Downstream genes''' - genes that are activated by other "upstream genes".

'''Ectoderm''' - outermost layer of germ cells in an early embryo.

'''Endoderm''' - innermost layer of germ cells in an early embryo.

'''Glial cells''' - non-neuronal cells that provide structure and protection to neurons as well as producing myelin.

'''Inductive signaling''' - a process whereby the secretion of factors from one cell or tissue triggers a response in another.

'''Lens vesicle''' - the cavity of invaginated ectoderm from the optic placode that will form the lens.

'''Macula''' - a highly pigmented, oval-shaped area located near the centre of the retina. Important for visual acuity.

'''Mesenchyme''' - undifferentiated, loose connective tissue.

'''Mesoderm''' - middle layer of germ cells in an early embryo.

'''Mesothelium''' - the epithelial layer of the mesoderm.

'''Myelinisation''' - development of a myelin sheath around a nerve fibre.

'''Neural crest''' - a portion of the ectoderm situated next to the neural tube.

'''Neural groove''' - a large invagination on the dorsal surface of the embryo which will close off and form the neural tube.

'''Neural tube''' - hollow structure that results from the folding of the neural plate and eventually forms the central nervous system.

'''Neuroblastic layer''' - a layer of immature cells that differentiate to form either glial cells or neurons. The retina has two of these (an inner and outer).

'''Neuroectoderm''' - portion of the ectoderm that develops to form the central and peripheral nervous systems.

'''Optic chiasm''' - the point at which the optic nerves meet and cross over.

'''Optic cup''' - the structure that is formed after the optic vesicle folds in upon itself. This will form the retina.

'''Optic globe''' - a term that refers to the optic cup, lens vesicle and surrounding mesenchyme collectively.

'''Optic placode''' - area of thickened ectoderm that gives rise to the lens of the eye.

'''Optic stalk''' - a long, narrow cavity that will produce the optic nerve.

'''Optic vesicle''' - a cavity that buds off from the neural tube and gives rise to the optic cup.

'''Upstream genes''' - genes that activate one or more other "downstream genes".

'''Vascularise''' - to invade with blood vessels.

==Image Gallery==
<gallery>
Image:Eye_diagram_bandw.jpg‎ | Basic structure of the human eye.
Image:Stage14 sem2b-limb.jpg | A Stage 14 embryo showing the location of an otic placode.
Image:Stage 13 image 060.jpg | A cross section showing the organisation of the developing brain, the optic vesicle and the lens (optic) placode.
Image:Formation of the optic vesicle 1.jpg | Early formation of the optic vesicle from the neural groove.
Image:Formation of the optic vesicle 2.jpg | The optic vesicle at a later stage, showing the optic stalk.
Image:Formation of the optic nerve and chiasm 1.jpg | A recognisable brain and eye structure in later development.
Image:Formation of the optic cup 1.jpg | Mechanism of optic cup formation.
Image:Formation of the optic cup 2.jpg | Layers of the optic cup in retina development.
Image:Formation of the retina 1.jpg | Cross-section of the primitive retina showing cell types and layers.
Image:Formation of the retina 2.jpg | Cross-section of a developed retina showing cell types and layers.
Image:Formation of the lens 1.jpg | The importance of the optic cup in lens differentiation.
Image:Formation of the lens 2.jpg | The lens placode separates from the ectoderm and migrates into the mesoderm forming the lens vesicle.
Image:Formation of the choroid and sclera 1.jpg | The choroid and sclera derives from mesenchyme surrounding the optic cup.
Image:Formation of the eyelid 1.jpg | Small grooves in the ectoderm of the head - the precursors to an eyelid.
Image:Formation of the eyelid 2.jpg | The eye at an advanced stage of embryonic development. Note however, that the eyelids remain fused until much later.

</gallery>

==References==
<references/>

----

--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

----

{{2012Projects}}

2012 Group Project 1

2012-10-02T13:22:30Z

Z3254758: /* Cornea */

[[File:Eye_collage_2.jpg|right|830px]]

=Vision Development=

==Introduction==

Eyes are an important sensory organ shared across many different species and allow organisms to gather useful visual information from their environment. The visual system uses light from the environment and processes this information in the brain for visual perception. The visual system is complex, and is made up of various structures that work together to form vision. Each of the structures in the eye have specific tasks which contribute to the visual system. Knowledge of how the eye develops extends as far back as Aristotle more than 2000 years ago, and current knowledge shows that most of the crucial events of eye development occur in the embryological stage. The eye is an interesting model for studying the development of tissues in organisms, as it consists of cells from several parts of the embryo including the head ectoderm, neural ectoderm and mesoderm. From its many origins the cells come together and differentiate to produce the complex organ that is the eye. During this period there are many examples of inductive signaling, as the tissues coordinate their development throughout this elegant process.

The main anatomical structures of the eye are as follows:
{|
|
* Cornea

* Sclera

* Choroid

* Iris

* Ciliary body

* Lens

* Anterior chamber

* Posterior chamber

* Retina

* Optic nerve

|[[File:eye_diagram_bandw.jpg|right|250px|thumb|Basic structure of the human eye.]]
|}
[[File:Eyediagramcolour1.JPG|550px]]

==Research History==

=== '''Brief Timeline of Historical Developments on the Eye and its Embryology''' ===

{| width=800px
|-bgcolor="CEDFF2"
| width=100px|'''Time'''
| width=700px|'''Discovery'''

|-bgcolor="F5FAFF"
| '''Ancient Egyptians'''
| First to document cataracts. It is described as being 'the white disease of the eye' or 'darkening of the pupil.' <ref>Edwards, D.D. (1996). Ophthalmology before Hippocrates. In the History of Ophthalmology, ed. D.M. Albert and D.D. Edwards. Cambridge, Mass.: Blackwell Science.</ref> The Egyptians had some knowledge of the eye, however it is not known how much of the anatomy of the eye was known in their era.

|-bgcolor="CEDFF2"
| '''535 BC'''

|
Ancient Greek philosopher Alcmaeon conducted dissection of humans for the first time in recorded history. This included dissection of the eye. However, not much is known about which anatomical features he discovered. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17.">Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17.</ref>

|-bgcolor="F5FAFF"
| '''384- 322 BC'''

| [[File:Aristotle-eye.jpg|200px|thumbnail|The eye according to Aristotle.<ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "> Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau </ref> Note the lens is missing, and there are three vessels drawn that was believed to transport fluid to and from the eye.<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
]]
Aristotle performed dissections of animal embryos.<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

When Aristotle described the embryo of a ten day old chicken, he wrote "The eyes about this time, if taken out, are larger than beans and black; if their skin is removed the fluid inside is white and cold, shining brightly in the light, but nothing solid." <ref name="Magnus, H. (1998). Ophthalmology of the ancients. In J. Hirschberg (Ed.), The History of Ophthalmology: The monographs, Vol. 4, Part 1 (F.C. Blodi, Trans.) Bonn: Wayenborgh.">Magnus, H. (1998). Ophthalmology of the ancients. In J. Hirschberg (Ed.), The History of Ophthalmology: The monographs, Vol. 4, Part 1 (F.C. Blodi, Trans.) Bonn: Wayenborgh.</ref>

Aristotle believed that the eyes started forming during early embryogenesis, however, he also believed that the eyes are the last organs to form completely, and he incorrectly thought that the eyes shrink in later embryonic development. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press.">Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press.</ref> .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"

| '''340 BC'''

| Lens is thought to have been discovered by Hippocrates, due to his descriptions of the contents of the internal eye There has been studies in chick development later on by followers of Hippocrates. They claimed that eyes were visible in early embryogenesis. .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
|-bgcolor="F5FAFF"
|'''25 BC - 50 AD'''

| [[File:Celsus-eye.jpg|150px|thumb|The eye according to Celsus. <ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "/>
Note the lens is placed in the centre of the eye, in the vitreous.<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> ]]

Aulus Cornelius Celsus wrote a Roman medical text called 'De Medicina' in which he wrote that the lens was the part of the eye from which vision originated. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.">Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.</ref> Celsus also incorrectly drew the lens in the center of the globe in his diagram of the eye. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

|-bgcolor="CEDFF2"
| '''23-79 AD '''
|
Pliny the Elder said that the eye is the last of the organs to develop in the womb <ref name="Magnus, H. (1998). Ophthalmology of the ancients. In J. Hirschberg (Ed.), The History of Ophthalmology: The monographs, Vol. 4, Part 1 (F.C. Blodi, Trans.) Bonn: Wayenborgh."/>
|-bgcolor="F5FAFF"
| '''98-117 AD'''

| [[File:Rufus-eye.jpg|150px|thumb|The eye according to Rufus of Ephesus. <ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "/>
Note the lens is placed in the correct position, behind the iris of the eye <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> ]]

Rufus of Ephesus identified the lens as being located in the anterior part of the eye, close to the pupil. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

His diagram illustrates that he knew the correct position of the lens as being directly behind the iris, in the anterior part of the eye, and not in the centre as was previously depicted by others before him.

|-bgcolor="CEDFF2"
| '''130-200 AD'''

| [[File:Galen-eye1.jpg|150px|thumb|The eye according to Galen. <ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "/> ]]

Claudius Galen practised medicine in Rome. He wrote:

"1. Within the eye the principal orgran of sensation is the crystalline lens.

2. The sensation potential comes from the brain and is conducted via the optic nerves.

3. All other parts of the eyeball are supporting structures." <ref> Hirschberge, J. (1982). Antiquity, Vol. X in the History of Ophthalmology (F.C. Blodi, Trans.) Bonn: Wayenborgh. pp. 280 </ref>

Galen thought that the lens was produced from the vitreous. He also believed that the retina’s function was to give nourishment to the lens and vitreous, and to carry visual information to the brain from the lens. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

|-bgcolor="F5FAFF"

| '''1514-1564'''

| Andreas Vesalius published his anatomy book "De Humani Corporis Fabrica in 1543. He had the misconception that the lens was located in the centre of the eyeball. .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> He also wrote that the lens functioned "like a convex lens made of glass" <ref name="Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.">Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.</ref> pp. 48
|-bgcolor="CEDFF2"
| '''1535-1606'''

| Georg Bartisch correctly drew a diagram of the lens placed behind the iris in his book 'Ophthalmodouleia: das ist Augendienst'. <ref name="Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>
|-bgcolor="F5FAFF"

| '''1537-1619'''

| Fallopio Hieronymus Fabricius ab Aquapendente studied anatomy and embryology. He studied chicken embryos, and thought that chalazae (which comes from egg white) gives rise to the eyes. He also drew the lens directly behind the iris in a diagram in is book 'Tractatus de Oculo Visuque Organo. <ref name="Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

|-bgcolor="CEDFF2"
| '''1583'''

| Felix Platter published his book 'De corporis Humani Structura et Usu, after he performed dissections of human bodies. He believed that the retina is the primary visual organ in the eye. .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="F5FAFF"
| '''1619'''
| Scheiner is given credit to be the first person to correctly draw the diagram of the anatomy of the eye. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
|-bgcolor="CEDFF2"
| '''1672'''
| Marcello Malpighi described the embryonic development of the chicken. He drew many detailed diagrams of the chick eye. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1665'''
| Nicolaus Steno identified the choroid fissure in his study of a developing embryo of a chicken. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="CEDFF2"
| '''1754'''

| Albrecht von Haller studied the embryology of the eye. With help from his student Johann Gottfried Zinn, he contributed to the understanding of the development of the ciliary body, ciliary zonule, and their relationship with the lens and vitreous. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1817'''

| Christian Pander discovered the three embryonic germ layers, which he wrote about in his book. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/> Pander was the first to think of 'the optic vesicles as lateral evaginations' of the 'prosencephalon'; however, he was incorrect about the details regarding how 'the eye develops from these evaginations'. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="CEDFF2"
| '''1828-1837'''

| Karl Ernst von Baer studied embryology. He discovered that the optic vesicles were 'outgrowths of the embryonic forebrain' <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> which he believed was caused by pressure from fluids in the central nervous system. Von Baer also believed that the optic vesicle opens to form the pupil, and that fluid in the optic vesicle coagulates to form the vitreous body and lens. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1830'''

| Emil Huschke discovered that the lens forms from the invagination of the surface ectoderm. He concluded that the lens hence does not form ‘from the fluid of the optic vesicle’ <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> as previously thought.
|-bgcolor="CEDFF2"
| '''1832'''

| Emil Huschke wrote in his manuscript ‘Ueber die erste Entwinkenlung des Auges und die damit zusammenhängende Cyklopie’ that the lens capsule forms from the outer surface ectoderm, which detaches and moves back inward, which is later enclosed again by several membranes, such as by the cornea. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

Huschke also described how the optic cup and choroid fissure forms. He discovered that the optic vesicles are produced from the two-layered optic cup. However, he incorrectly described the destiny of the ‘individual optic cup layers’. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

|-bgcolor="F5FAFF"
| '''1838'''
| Matthias Jakob Schleiden and Theodor Schwann formulated the ‘cell theory’: “All living things are formed from cells, the cell is the smallest unit of life, and cells arise from pre-existing cells.” <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
|-bgcolor="CEDFF2"
| '''1839'''

| Theodor Schwann contributed a better understanding of the development of the lens through studying the foetus of a pig, which he wrote about in his book ‘Mikroskopische Untersuchungen Über Die Uebereinstimmung in Der Struktur Und Dem Wachsthum Der Thiere Und Pflanzen’. He wrote that the lens is made of ‘concentric layers’ of fibres which proceeds from an anterior to posterior direction. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1842'''
| Robert Remak gave the current names to the three embryonic germ layers: ectoderm, mesoderm and endoderm. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"
| '''1843'''
| Wilhelm Werneck published his book ‘Beiträge zur Gewebelehre des Kristallkörpers’. He wrote that the contents inside of the lens is not made of fluids, as was previously believed. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/> Werneck also discovered that the fibers of the lens continues to grow from the outside to the centre during embryogenesis. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

|-bgcolor="F5FAFF"
| '''1855'''

| Robert Remak wrote his book ‘Untersuchungen über die Entwickelung der Wirbelthiere’. He wrote about what he discovered in his studies of the development of the eye in the embryos of chickens, frogs, and rabbits. He wrote very descriptively about the embryology of lens formation, amongst other topics. He discovered that the ectoderm gives rise to the lens placode. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

|-bgcolor="CEDFF2"
| '''1858'''
| Henry Gray published his book 'Anatomy, Descriptive and Surgical'. He had also previously studied the embryonic development of the optic nerve and retina of chickens.
|-bgcolor="F5FAFF"
| '''1877'''
| Paul Leonhard Kessler wrote about the embryonic development of the lens in mice in his book ‘Zur Entwickelung des Auges der Wirbelthiere. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"
| '''1891'''
| Vincenzo Colucci studied newts and discovered their ability to regenerate the lens.<ref> Tsonis, P. A. (2001). Regeneration of the Vertebrate Lens and Other Eye Structures. eLS. (Online Publication). DOI: 10.1038/npg.els.0001102 </ref>
|-bgcolor="F5FAFF"
| '''1892'''
| Dr. Oscar Hertwig published his book ‘Text-Book of the Embryology of Man and Mammals. <ref> Hertwig, O. Text-book of the embryology of man and mammals. S. Sonnenschein 1901. (Translated from the 3d German ed. by Edward L. Mark.) </ref> It contains a very detailed description of the development of the eye, according to the findings at that time. [http://embryology.med.unsw.edu.au/embryology/index.php?title=Book_-_Text-Book_of_the_Embryology_of_Man_and_Mammals_16-2#The_Development_of_the_Eye]
|-bgcolor="CEDFF2"
| '''1895'''
| Gustav Wolff also independently studied newts and discovered their ability to regenerate the lens. .<ref> Tsonis, P. A. (2001). Regeneration of the Vertebrate Lens and Other Eye Structures. eLS. (Online Publication). DOI: 10.1038/npg.els.0001102 </ref>

|-bgcolor="F5FAFF"

| '''1900'''
| Carl Rabl published his book ‘Uber den Bau und die Entwicklung der Linse’. He wrote about the development of the lens in mammals, fish, birds, reptiles, and amphibians. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"
| '''1901'''
| Hans Spemann published his findings from his experimental studies about the formation of the lens in the frog. He found that the optic cup needed to be in contact with the ectoderm for normal development of the eye. <ref> Spemann, H. (1901). Über Correlationen in der Entwicklung des Auges. Verhand. Anat. Ges. 15: 61-79. </ref> <ref> Saha, M. (1991). Spemann seen through a lens. In Gilbert, S. F. (ed.). A Conceptual History of Modern Embryology. Plenum Press, NY. pp. 91-108.</ref>
|-bgcolor="F5FAFF"
| '''1906'''
| Brown ‘s book “The Embryology Anatomy and Histology of the Eye” was published. It contained detailed descriptions of the embryonic development of the eye according to the knowledge current at that time, mainly based on observations from embryos of rabbits and chickens. <ref> Brown, E.J. (1906). The Embryology Anatomy and Histology of the Eye. Chicago: Hazlitt & Walker. 1906 </ref>

|-bgcolor="CEDFF2"
| '''1907'''

| John Clement Heisler published his book ‘A Text-book of embryology’. It contains a chapter detailing the embryonic development of the eye, according to the knowledge current at that time. The book’s copyright has expired, so it can be viewed free online: [http://archive.org/details/atextbookembryo01heisgoog]

Julius Kollman also published his book 'Atlas of the Development of Man'. It contained very detailed description and illustrations showing the embryonic development of the human according to the knowledge current at that time. His illustrations were reused by many others after his time and built upon for further refined understanding of the embryology of the human.

Here are examples of Julius Kollman's excellent illustrations showing eye development in various stages:

'''Formation of Primary Optic Vesicle:'''
<gallery>
File:Kollmann691.jpg|The blue part at the bottom is the endoderm. The pink middle layer is the mesoderm. The top yellow layer is the ectoderm. The fold labelled as 'augenfeld' is the place where the optic vesicle will form.
File:Kollmann692.jpg|The eye area (augenfeld) is a bowl shaped bulge still located on the side walls.
File:Kollmann693.jpg| The neural tube is shown after removal of all of the ectoderm and ventral organs, such as heart, gut tube, etc. The primary optic vesicle forms a slightly flattened hollow protrusion on the forebrain.
File:Kollmann694.jpg|The lateral surface of the primary optic vesicle is slightly depressed, showing the first sign of the emergence of the secondary optic vesicle
</gallery>

'''Development of Lens:'''

<gallery>
File:Kollmann695.jpg|The bulging lateral wall of the primary optic vesicle is covered by a fairly well demarcated lens plate, a direct continuation of the ectoderm. Between the optic vesicle and the lens pit are some flattened spindle-shaped cells. In the adjoining mesoderm are cross-sections of capillaries.
File:Kollmann697.jpg|The lens still hangs together with the ectoderm. The primary eye vesicle is indented with respect to the lens. Between the lens and the lateral plate of the optic vesicle is a narrow space, which allows area to further develop later.
File:Kollmann698.jpg|4th Week of development. The internal organisation shows the secondary optic vesicle. A: The rear wall of lens is noticeable and is enveloped by mesoderm. B: The edges of the lens pit is already grown and the lens vesicles are formed, which is still related to the remaining ectoderm.
File:Kollmann699.jpg|The lens has now cut off from the ectoderm, but is still very superficial. Between it and the lateral lamina of the optic cup, there is a considerable space. The eye stalk has become longer and is enclosed together with the optic cup and lens of the mesoderm. The cornea, sclera and choroid make gradual development.
</gallery>

|-bgcolor="F5FAFF"

| '''1921'''
| Bailey and Miller published their textbook “Text-Book of Embryology “. <ref> Bailey, F.R. and Miller, A.M. (1921). Text-Book of Embryology. New York: William Wood and Co. (Note- This book is only at an early edited stage)</ref> It contains detailed description of the development of the embryonic eye according to the knowledge current at that time. [http://embryology.med.unsw.edu.au/embryology/index.php?title=Book_-_Text-Book_of_Embryology_18]

|-bgcolor="CEDFF2"
| '''1925'''

| Mann published his research article, in which he gives a detailed account of the development of the human iris. He divided the development of the iris into four stages: weeks 4-7 (before the ectodermal iris forms or before the anterior chamber forms); weeks 7-11 (anterior chamber appears, and mesodermal iris forms); weeks 11-12 (ectodermal iris forms); 3-8 months (muscles of the pupil forms from ectodermal iris, and the central portion of the mesodermal iris atrophies to make the pupil clear). <ref name="PMID18168466"><pubmed>18168466</pubmed></ref>
O Leser also published an article detailing the development of extraocular muscles in mammals he studied. <ref name="PMID18168498"><pubmed>18168498</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1939'''
| Holtfreter <ref> Holtfreter, J. (1939). Gewebeaffinitat, ein Mittel der embryonalen
Formbildung. Arch. Exp. Zellforsch. 23, 169-209. </ref> studied amphibians and observed that that the development of the eye stops at the ‘optic vesicle stage’ if there is no contact ‘with the epidermis and neural crest driven mesenchyme’. <ref name=”PMID11023863”><pubmed>11023863</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1955'''
| Barber published his book ‘Embryology of the human eye’. <ref> Barber AN: Embryology of the human eye. St. Louis. CV Mosby 1955</ref> In contains detailed descriptions of the embryological development of the human eye according to the knowledge current at that time. It contains many photographs of the eye at different stages of development.

|-bgcolor="F5FAFF"
| '''1957'''
| Coulombre studied a chicken embryo to find the role of intraocular pressure in the development of the chick’s eye, especially in regards to its control of the size of the eye structures. <ref name="PMID13469954"><pubmed>13469954</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1958'''
| Coulombre studied the development of the cornea and how it develops its transparency. <ref name="PMID13563560"><pubmed>13563560</pubmed></ref> He also studied the development of corneal curvature. <ref name="PMID 13519969"><pubmed> 13519969</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1962'''
| Coulombre studied the development of the conjunctival papillae and scleral ossicles. <ref name="PMID 14023393"><pubmed> 14023393</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1963'''
| Coulombre studied the development of lens fibers and their orientation. <ref name="PMID14077035"><pubmed>14077035</pubmed></ref> He also studied the development of pigmented epithelium. <ref name="PMID14023394"><pubmed>14023394</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1964'''

| Coulombre further studied the development of the lens to determine the role of the lens in eye growth. <ref name="PMID14189921"><pubmed>14189921</pubmed></ref> He also studied the role of thyroid in the development of the cornea and the development of corneal transparency. <ref name="PMID14211912"><pubmed>14211912</pubmed></ref> Mann also published his work called ‘The development of the human eye’, which contains detailed description of the embryonic development of the eye according to current knowledge at that time. <ref> Mann I. The development of the human eye. New York: Grune and Stratton 1964</ref>

|-bgcolor="CEDFF2"
| '''1965'''
| Coulombre published his findings regarding the regeneration of the neural retina from pigmented epithelium in the embryo of chickens. <ref name="PMID5833111"><pubmed>5833111</pubmed></ref> Smelser also published his findings on the embryological development and morphology of the lens. <ref name="PMID14340157"><pubmed>14340157</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1966'''

| Formation of the face and orbit occurs from the differentiation of neural crest cells. <ref name="PMID5969670"><pubmed>5969670</pubmed></ref> O’Rahilly also published findings of the development of the eye in the early stages of human embryos. <ref> O'Rahilly, R. 1966 The early development of the eye in staged human embryos. Contr. Embry. Carnegie Inst., Wash., 38: 1–42</ref>

|-bgcolor="CEDFF2"
| '''1968'''
| Findings of the postnatal development of the retina of rats was published. <ref name="PMID5640327"><pubmed>5640327</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1969'''

| Mann again published his work called ‘The development of the human eye’. He stated that that the lens in humans forms completely from the ectoderm. <ref name=”Mann I. The Development of the Human Eye. New York, USA: Grune & Stratton, Inc; 1969”> Mann I. The Development of the Human Eye. New York, USA: Grune & Stratton, Inc; 1969</ref> Coulombre also studied the development of the lens, and took note of its size, shape and orientation throughout its developmental stages. <ref name="PMID 5772716"><pubmed> 5772716</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1970'''
| Coulombre again further studied the regeneration of the neural retina from pigmented epithelium of embryos of chickens. <ref name="PMID 5472476"><pubmed> 5472476</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1971'''

| Coulombre further studied the development of the lens. This time he focused on analysing the histological mechanisms in the reconstitution of the lens from implanted lens epithelium. <ref name="PMID 4925671"><pubmed> 4925671</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1973'''
| A research article was published, detailing the embryonic development of the retina of humans. <ref name="PMID 6650859"><pubmed> 6650859</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1976'''

| Geeraets published his observations of the closure of the embryonic optic fissure in golden hamsters, using the electron microscope. <ref name="PMID 1266776"><pubmed> 1266776</pubmed></ref> Kornneef also published an article based on his studies of the development of connective tissue in the human orbit. <ref name="PMID 1020699"><pubmed> 1020699</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1981'''
| A research article was published detailing how myelin forms in the optic nerve of humans. <ref name="PMID 7224936"><pubmed> 7224936</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1983'''
| O’Rahilly’s further research developments was published, reporting the timing and sequence of events in the development of the embryonic human eye. <ref name="PMID 6650859"><pubmed> 6650859</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1990'''

| Van Driell et al. <ref>Driell, D. Van; Provis, J.M.; Billson, F.A.: Early differentiation of ganglion, amacrine, bipolar and Muller cells in the developing fovea of the human retina. J. Comp. Neurol. 291: 203-219.</ref> studied the manner in which amacrine, bipolar, retinal ganglion cells, and Muller cells differentiate in the developing fovea of the retina of a 15-week old human foetus. <ref name="PMID1628748"><pubmed>1628748</pubmed></ref> Tripathy also published an article providing evidence that the lacrimal glands in humans originates from the neuroectoderm. <ref name="PMID2406219"><pubmed>2406219</pubmed></ref>

|}

==Development, Structure and Function of Ocular Components==

The eye itself is formed from several components; notably the optic placode of the head ectoderm, the optic vesicle from the neural tube, and mesenchyme from the mesoderm and neural crest cells. The optic placode contributes the lens to the eye, the optic vesicle gives rise to layers of the retina, while the mesenchyme will produce the ciliary body, iris, choroid and sclera.<ref>http://www.vetmed.vt.edu/education/curriculum/vm8054/eye/EMBYEYE.HTM</ref> Cells from the neural tube will also produce the optic nerve, which receives nerve impulses from the retina of the eye. Eyes initially form as laterally paired structures and migrate medially in the human embryo. In other animals such as birds and lizards, the eyes do not migrate and develop laterally on the head. The optic placodes become prominent on the surface of the embryo at approximately Stage 14 of development.

[[File:Stage14 sem2b-limb.jpg|200px|thumb|left|A Stage 14 embryo showing the location of an otic placode.<ref name="http://embryology.med.unsw.edu.au/embryology/index.php?title=ANAT2341_Lab_6_-_Early_Embryo">http://embryology.med.unsw.edu.au/embryology/index.php?title=ANAT2341_Lab_6_-_Early_Embryo</ref>]] [[File:Stage 13 image 060.jpg|400px|thumb|center|A cross section showing the organisation of the developing brain, the optic vesicle and the lens (optic) placode.<ref name="http://embryology.med.unsw.edu.au/embryology/index.php?title=ANAT2341_Lab_6_-_Early_Embryo"/>]]

===Optic Nerve===

The optic nerve consists of nerve fibres that transmit information from the retinal photoreceptor cells to the brain. The optic nerve is formed from the optic stalk, which develops as the optic vesicle migrates from its origin in the neural tube to its destination - the surface ectoderm - where it will fuse with the optic placode (also known as the lens placode, which will contribute the lens to the eye).<ref name="PMID11687490"><pubmed>11687490</pubmed></ref>

[[File:Formation of the optic vesicle 1.jpg|400px|thumb|left|Fig. 1: Early formation of the optic vesicle from the neural groove.]] [[File:Formation of the optic vesicle 2.jpg|400px|thumb|center|Fig. 2: The optic vesicle at a later stage, showing the optic stalk.]]

As can be seen in Figure 1 above, the optic vesicle forms from the neural tube. However, note that the neural tube has not yet closed, and is still the neural groove at this point. Figure 2 then shows the optic vesicle at slightly later stage in the same simplified cross-section of the embryo, as it migrates from the neural tube to the surface ectoderm. Note the presence of the optic stalk which links the optic vesicle to the neural tube. Later in development, this primitive structure will become the optic nerve, which will link the eye to the brain.

The nerve fibres themselves will initially originate from the retinal ganglion cells in the eye during week 6.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008">Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008</ref> After two weeks, these fibers will have grown along the inner wall of the optic stalk and have reached the brain. They grow both in length and width, with the nerve fibres filling the hollow optic stalk to form the solid optic nerve. More than one million nerve fibers will eventually make up the optic nerve, along with glial cells which arise from the inner wall of the optic stalk itself.<ref><pubmed>1451666</pubmed></ref> Myelinisation of the optic nerve begins much later in development at around 7 months, beginning at the optic chiasm and moving towards the eye.<ref><pubmed>7224936</pubmed></ref> The optic chiasm forms just before the nerves reach the brain, and is where half the nerve fibres from each eye will cross over to the opposite side of the brain. This is demonstrated in Figure 3. Note the crossing over of the optic nerves just before they enter the brain, at the optic chiasm. This organisation is now much more familiar, with the eyes near the ectoderm and the optic nerve leading through the mesoderm to the brain buried deep in the embryo.

[[File:Formation of the optic nerve and chiasm 1.jpg|400px|thumb|center|Fig. 3: A recognisable brain and eye structure in later development.]]

===Retina===

The retinal component of the eye is formed when the optic vesicle folds in upon itself, forming the optic cup (see Figure 4). In doing so it creates two layers - an inner wall and an outer wall of the optic cup (Figure 5). These two layers of the optic cup will give rise to the two layers of the retina - the inner neural retina, and the outer pigmented epithelium.<ref name="PMID11687490"/> Note the existence of the space between the two layers of the retina. This is known as the intraretinal space and disappears by the 7th week of development, however the two layers never completely fuse and can become separated as a result of physical trauma to the head - leading to a detached retina and loss of vision.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/>

The inner wall of the optic cup, which will give rise to the neural retina, consists of a layer of pseudostratified cells (see Figure 6) that later differentiate into rod, cone, bipolar, ganglion, horizontal, amacrine and glial cells of the retina (Figure 7).<ref name="PMID18168748"><pubmed>18168748</pubmed></ref> The outer wall of the optic cup consists of a layer of cuboidal cells that contain melanin - the light absorbing pigment. The function of this layer is to absorb light and prevent internal reflection of light within the eye, which would impair our ability to form distinct images. Interestingly, in some animals such as cats, this layer actually reflects light intentionally to increase the amount of light available to the eye in low-light conditions. This is why cats seem to have eyes that glow in the dark.<ref>http://dialspace.dial.pipex.com/agarman/bco/fact4.htm</ref>

[[File:Formation of the optic cup 1.jpg|400px|thumb|left|Fig. 4: Mechanism of optic cup formation.]] [[File:Formation of the optic cup 2.jpg|400px|thumb|center|Fig. 5: Layers of the optic cup in retina development.]]

The inner wall itself is divided into two components - the inner neuroblastic layer and the outer neuroblastic layer (see Figure 6). The outer neuroblastic layer forms the rod and cone cells while the inner neuroblastic layer forms the remaining cell types found in the retina - the bipolar, ganglion, horizontal, amacrine and glial cells (Figure 7).<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/> The organisation of the retina is interesting in that incoming light passes through several layers of these neural retina cells before it is detected by rod and cone cells at the back of the retina, and then nerve signals are passed back through the layers of neural retina cells that the light just passed through moments before - a seemingly strange design that the eye does not share with man-made light-capturing devices such as a camera (imagine putting the wires in front of the image sensor!).

Differentiation of the neuroblastic layers into neural retina cells occurs in a pattern both within the layers and across the retina. Cells differentiate from the inner neuroblastic layer to the outer neuroblastic layer, and differentiate from the central retina to the peripheral retina.<ref name="PMID18168748"/> The macula is first identifiable in week 22 when ganglion cells start to form multiple rows, and the primitive fovea begins to form at approximately the same time as a depression in the macula.<ref><pubmed>6462623</pubmed></ref> It is not until 15-45 months after birth that this area becomes exclusively populated by cone cells and becomes the fovea centralis - the area of the retina with the highest visual acuity.

[[File:Formation of the retina 1.jpg|400px|thumb|left|Fig. 6: Cross-section of the primitive retina showing cell types and layers.]] [[File:Formation of the retina 2.jpg|400px|thumb|center|Fig. 7:Cross-section of a developed retina showing cell types and layers.]]

===Ciliary Body===

The ciliary body consists of ciliary processes and three portions of fibres that constitute the ciliary muscles. It functions to maintain normal eye physiology as well as playing a direct role in accommodation.

During development, the ciliary processes form slightly posterior to the iris, developing from part of the anterior rim of the optic cup. It is thought that the folded structure of the ciliary processes is brought about by intraocular pressure and specific signalling pathways.<ref name="PMID16959249"><pubmed>16959249</pubmed></ref> While the ciliary muscles and the endothelial cells of the ciliary blood vessels are chiefly formed by mesenchymal cells<ref><pubmed>16249499</pubmed></ref>, the neural crest and neuroectoderm also contribute to their development.<ref><pubmed>12127103</pubmed></ref> The normal development of the ciliary body is dependent on the correct expression of bone morphogenetic protein (BMP)-4, which is a member of the transforming growth factor-β superfamily.<ref><pubmed>1222340</pubmed></ref> Napier and Kidson (2007) summarised numerous genes that have been associated with ciliary body development, however their direct roles have not been well documented.<ref name="PMID16959249"/>

===Iris===

The iris is a thin layer that develops at the end of the third month of development and is derived from the anterior rim of the optic cup. The stroma of the iris develops from cells of neural crest cell origin.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/> The muscles that are responsible for the dilation and constriction of the pupil (dilator pupillae and sphincter pupillae muscles) form from the neuroectoderm of the optic cup. These cells are initially epithelial cells that then transform into smooth muscle cells. <ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"></ref>. The invagination of the optic vesicle which creates the optic cup, also causes the formation of the optic cup lip. This is the region of the where the epithelium doubles back, separating the outer pigmented layer and the inner nonpigmented layer. This is the edge of the iris that borders on the pupil<ref><pubmed> Retinal and anterior eye compartments derive from a common progenitor pool in the avian optic cup</pubmed></ref>.

The final colour of the iris is not evident until the postnatal period. It is determined by a number of genes including IRF4, SLC24A4 and MATP<ref><pubmed>19710684</pubmed></ref>. Other features such as crypt frequency, furrow contractions, presence of peripupillary pigmented ring, and number of nevi also become evident during development<ref><pubmed>21835309</pubmed></ref>.

Mutations in Pax6 have been shown to cause partial or complete loss of the iris <ref><pubmed>12386935</pubmed></ref>.

===Cornea===

The cornea is the transparent, avascular, most anterior portion of the eye. It is responsible for conducting light into the eye and focusing it on to the retina, as well as maintaining the rigidity of the eyeball. It consists of 5 layers- the epithelium, Bowman’s layer, stroma, Descemet’s membrane and the endothelium.

The epithelium and endothelium of the cornea first appear during the 5th week of gestation. The epithelium of the external surface of the cornea is derived from surface ectoderm, while the mesenchyme is derived from the mesoderm<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"/>. The endothelium is a two-cell cuboidal layer which is made up of differentiated neural crest cells that were initially from the optic cup. By week 8 the endothelial cells begin to secrete a basement membrance which later forms Descemet’s membrane<ref><pubmed>6511224</pubmed></ref>. At approximately 16 weeks gestation the Bowman’s membrane begins to form from the thickening of the stroma that is located under the corneal epithelium<ref>Riordan-Eva P, Whitcher JP. Vaughn and Asbury's General Ophthalmology, Lange Medical Books/McGraw Hill. 2004:25–27</ref>. During the third month glycosaminoglycans secreted by fibroblasts form the ground substance of the cornea, with collagen fibrils and keratan sulphate also appearing around this time. Shortly after this tight junctions form between the endothelial cells<ref><pubmed>19481138</pubmed></ref>. Fibroblast growth factor causes the epithelial cells to proliferate<ref><pubmed>20105280</pubmed></ref>.

Towards the end of the gestational period the cornea becomes larger due to the production of aqueous humor<ref>Yanoff M, Duker JS. Ophthalmology. Mosby; St. Louis, MO: 2004</ref>. The final transparent structure develops because hyaluronidase removes hyaluronic acid, thyroxine causes dehydration of the stroma, and the entire structure becomes avascular<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/>. Numerous genes have been implicated in the development of the cornea, these include, but are not limited to, PAX6, PITX2, FOXC1, MAF, TMEM114, SOX2, OTX2 and BMP4<ref><pubmed>18637741</pubmed></ref>.

===Lens===

The lens has its origin from the optic placode, which develops on the ectodermic surface of the embryo and migrates both medially and inwards into the embryo. The lens allows accommodation of the eye, and adjusts its thickness in order to focus on near or far objects. The study of lens development was one of the first to highlight the importance of inductive signaling in development, with Spemann's pioneering work at the start of the 20th century, finding that the absence of retinal development resulted in the absence of lens formation.<ref name="PMID11687490"/> Indeed, it has been consistently shown that the interaction of the migrating optic vesicle with the surface ectoderm of the head is vital in producing differentiation of the lens.<ref name="PMID15558475"><pubmed>15558475</pubmed></ref> The mechanism of interaction is complex but basically involves upstream genes switching on downstream genes, with the genes eventually producing specialised proteins which constitute the lens. The whole process starts with the signaling molecules from the optic cup initiating a thickening of the surface ectoderm of the head (Figure 8). It is thought that this region of specific ectoderm is responsive to the signaling molecules, as lens formation is incomplete or absent when ectoderm from the lateral portion of the embryo (i.e. non-head ectoderm) is exposed to the same inductive signaling processes.<ref name="PMID9216064"><pubmed>9216064</pubmed></ref> Pax6 has been shown to be one of the major genes required for differentiation of the lens, which in turn switches on transcriptional genes such as Sox 1, 2 and 3 among others - producing water-soluble proteins called crystallins - responsible for giving the lens its transparency and refractive properties.<ref name="PMID9609835"><pubmed>9609835</pubmed></ref>

[[File:Formation of the lens 1.jpg|400px|thumb|left|Fig. 8: The importance of the optic cup in lens differentiation.]] [[File:Formation of the lens 2.jpg|400px|thumb|center|Fig. 9: The lens placode separates from the ectoderm and migrates into the mesoderm forming the lens vesicle.]]

The lens placode invaginates from the head ectoderm and migrates into the mesoderm (Figure 9). Once this structure (now known as the lens vesicle) is in place opposite the optic cup, the combined structure is referred to as the optic globe and resembles a recognisable eye structure. The lens continues to differentiate further, as mentioned above, through the formation of crystallin proteins, which give the lens its unique properties and allows for the fine control over the degree of refraction that takes place.

===Aqueous Chambers===

There are both anterior and posterior aqueous chambers of the eye which contain aqueous humour. A space develops in the mesenchyme situated between the lens and cornea to form the anterior aqueous chamber. The mesenchyme located superficially to this chamber forms the mesothelium as well as the transparent portion of the cornea.

The posterior chamber develops from a similar space in the mesenchyme, however it is located between the iris and the lens. The anterior and posterior chambers are able to communicate with one another once the papillary membrane vanishes and the pupil is formed. This channel is known as the scleral venous sinus.<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011">Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011</ref>

Contained within the aqueous chambers is aqueous humor. The production of aqueous humor is dependant on the development of the ciliary body. It is produced in the ciliary processes and it’s production is a metabolic process driven by the delivery of oxygen and the removal of wastes via the ciliary circulation<ref><pubmed>20801226</pubmed><ref>.

===Cornea===

The cornea is the transparent, avascular, most anterior portion of the eye. It is responsible for conducting light into the eye and focusing it on to the retina, as well as maintaining the rigidity of the eyeball. It consists of 5 layers- the epithelium, Bowman’s layer, stroma, Descemet’s membrane and the endothelium.

The epithelium and endothelium of the cornea first appear during the 5th week of gestation. The epithelium of the external surface of the cornea is derived from surface ectoderm, while the mesenchyme is derived from the mesoderm<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"/>. The endothelium is a two-cell cuboidal layer which is made up of differentiated neural crest cells that were initially from the optic cup. By week 8 the endothelial cells begin to secrete a basement membrance which later forms Descemet’s membrane<ref><pubmed>6511224</pubmed></ref>. At approximately 16 weeks gestation the Bowman’s membrane begins to form from the thickening of the stroma that is located under the corneal epithelium<ref>Riordan-Eva P, Whitcher JP. Vaughn and Asbury's General Ophthalmology, Lange Medical Books/McGraw Hill. 2004:25–27</ref>. During the third month glycosaminoglycans secreted by fibroblasts form the ground substance of the cornea, with collagen fibrils and keratan sulphate also appearing around this time. Shortly after this tight junctions form between the endothelial cells<ref><pubmed>19481138</pubmed></ref>. Towards the end of the gestational period the cornea becomes larger due to the production of aqueous humor<ref>Yanoff M, Duker JS. Ophthalmology. Mosby; St. Louis, MO: 2004</ref>. The final transparent structure develops because hyaluronidase removes hyaluronic acid, thyroxine causes dehydration of the stroma, and the entire structure becomes avascular<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/>. Numerous genes have been implicated in the development of the cornea, these include, but are not limited to, PAX6, PITX2, FOXC1, MAF, TMEM114, SOX2, OTX2 and BMP4<ref><pubmed>18637741</pubmed></ref>.

===Choroid and Sclera===

The choroid and sclera are adjacent layers that surround the eye and act to vascularise and protect the eye respectively. They are formed from neural crest and mesoderm-derived mesenchyme which condenses around the optic cup and lens vesicle between weeks 5 and 7 of development to form a primitive eyeball structure known as the optic globe.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/> Blood vessels first start to appear in the choroid layer at approximately week 15, and arteries and veins can be distinguished by week 23.<ref>Development of the Choroid and Related Structures, K. Sellheyer, Eye (1990) 4, 255-261</ref> Inductive processes are thought to play a vital role during formation of the choroid and sclera; with the retinal pigmented epithelium inducing differentiation of the surrounding mesenchyme while at the same time the neural crest-derived mesenchyme contributing components to the retinal pigmented epithelium such as melanocytes.<ref name="PMID1628748"/> In addition to having functional roles themselves, the primitive choroid and sclera also contribute components to the developing ciliary body and cornea (Figure 10). In the adult eye, the choroid is continuous with the ciliary body and the sclera with the cornea.

[[File:Formation of the choroid and sclera 1.jpg|400px|thumb|center|Fig. 10: The choroid and sclera derives from mesenchyme surrounding the optic cup.]]

===Eyelids===

The eyelids are ectodermal and mesodermal in origin and are an extension of the skin which covers and protects the eye. Eyelid formation can be first noted during week 5 when small grooves develop in the surface ectoderm (Figure 11).<ref><pubmed>7364662</pubmed></ref> These small grooves deepen and extend into the mesoderm and the primitive eyelid structures grow towards one another, eventually fusing together during week 8.<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"/> It is not until week 26-28 that the eyelids will separate again. The ectoderm reflects over the developing cornea to form the conjunctival sac, a space that is filled by secretions from the lacrimal gland in order to allow smooth motions of the eyelid over the eye and also to clean the cornea and prevent accumulation of particles on the eye that may disrupt vision. By the time the eyelids separate, the eye has all its major components present (Figure 12), and further development consists mainly of growth and vascularisation.

[[File:Formation of the eyelid 1.jpg|400px|thumb|left|Fig.11: Small grooves in the ectoderm of the head - the precursors to an eyelid.]] [[File:Formation of the eyelid 2.jpg|400px|thumb|center|Fig. 12: The eye at an advanced stage of embryonic development. Note however, that the eyelids remain fused until much later.]]

===Lacrimal Glands===

Lacrimal glands initially develop from budding of the conjunctival epithelium near the superolateral portion of the eye. The mesenchymal cells that surround these buds are of neural crest origin, and the budding continues until the mature gland is formed.<ref><pubmed> 9882499</pubmed></ref> These glands are responsible for the production of tears however they do not start to function until 1-3 months after birth.

==Current Research==

*more info will be added soon!!

===GABA Maintains the Proliferation of Progenitors and Non-Pigmented Ciliary Epithelium===

<pubmed>22590629</pubmed>

{| width=800px
|-
| width=450px|
| width=350px|

|-
| GABA is an ‘inhibitory neurotransmitter’ in the central nervous system of adults. <ref name="PMID22590629"><pubmed>22590629</pubmed></ref> It is responsible for controlling proliferation of stem cells and progenitor cells. The authors of this article <ref name="PMID22590629"/> was interested to find the effects of GABA on proliferation of progenitor cells and non-pigmented ciliary epithelial cells (NPE) in the retina. Their study focused on progenitor cells and non-pigmented epithelium of the ciliary body in chickens. Non-pigmented epithelial cells in chickens arise from the neuroepithelium of the optic cup. They share similar functions as progenitors of the early retina, such as expression of Chx10 and Pax6 genes. It is not agreed upon whether epithelial cells of the ciliary body have stem cell properties. However, it has been found that these cells can be cultured and transplanted into retinas that are injured, in order to replace neurons that were previously lost. However, there is not much known about what factors regulate the proliferation of stem cells. Hence the authors were interested in finding the effects of GABA on proliferation of retinal cells. Their results showed that non-pigmented epithelial cells in chickens ‘express extrasynaptic-like GABAA receptors’ that have the ability to regulate cell proliferation. It has been found that inhibiting these ‘GABAA receptors’ also causes a decrease in proliferation of retinal progenitor cells and non-pigmented epithelial cells in 'the intact E8 retina’. <ref name="PMID22590629"/>

|
[[File:Gaba-effects-retina.JPG|thumbnail|250px|'''GABAA receptor mediated effects on retinal progenitor cell proliferation'''
]]
|}

-------------------

===The impact of visible light on the immature retina===

<pubmed>22405869</pubmed>

The authors mentioned in this article <ref name="PMID22405869"><pubmed>22405869</pubmed></ref> that they were interested in investigating the effect of light on postnatal eye development in mice, because mice are born with fused eyelids, which separate 12 days after birth. Before the eyelids separate, the retina develops in mice with very little radiation from light. It is believed that the darkness plays a role in the development of the retina in mice, which is why their eyelids are fused for 12 days after birth. Therefore the authors were interested to see what effect light would have on postnatal retinal development of mice, with special interest in retinal ganglion cells (RGC). In their experiment, they surgically opened the eyelids on the right eyes of some of the mice to expose them to visible light 12 hours per day, while they left some other mice in the dark after surgical separation of their eyelids. They also kept the left eyes of the mice naturally fused as controls in the experiment. Their results showed that early light exposure in mice causes a decrease in retinal ganglion cells because it affects cellular apoptosis in the retina. The authors also observed that early exposure to light in mice causes lumican mRna transcription to resume and to quickly increase. (Lumican normally stays silent in retina after birth).

---------

===MIP/Aquaporin 0 Represents a Direct Transcriptional Target of PITX3 in the Developing Lens===

<pubmed>21698120</pubmed>

{| width=800px
|-
|PITX3 plays a siginificant role in the development of lens in vertebrates. If there is a deficiency is PITX3, it causes a range of problems in humans such as microphthalmia, Peter’s anomaly, or isolated cataracts. Mutation of PITX3 also causes degeneration of the lens in zebrafish and mice. It is therefore important to understand what factors may affect the decrease in PITX3, as a normal level of PITX3 is needed to maintain normal eye development. The authors wanted to investigate specific genes which are affected by PITX3. Previous research has shown that MIP and Aquaporin causes defects in the lens in both mice and humans. MIP and Aquaporin are targeted by PITX3, so their imbalance is interrelated in the cause of defects in the lens. Therefore it has been previously proven that PITX3 is needed for normal development of the lens. However, there has not been much information previously known regarding the exact effect that PITX3 has, or the specific genes it targets. Since MIP and Aquaporin is common genes found in humans, mice and zebrafish, the authors <ref name="PMID21698120"><pubmed>21698120</pubmed></ref> chose to study these genes to understand the pathway that PITX3 takes and its exact involvement in the development of the lens. Their results proved that deficiency in MIP and Aquaporin indeed affects normal development of the lens, and it is indeed related to deficiency in PITX3. However, there is still more research needed to understand PITX3 and the genes it interacts with, and their effect in ocular development.

|
[[File:Mip1-expression-in-pitx3.jpg|thumbnail|250px|'''Analysis of mip1 expression in pitx3-mo and control embryos via in situ hybridization and RT-PCR''']]
|}

-----------

<pubmed>22496813</pubmed>

This research <ref name="PMID22496813"><pubmed>22496813</pubmed></ref> studied c-Jun N-terminal Kinase (JNK) activation in the retina of newborn rats

[[File:JNK1.png]]

<pubmed>20544023</pubmed>

<pubmed>20459797</pubmed>

[http://www.advancedcell.com/patients/clinical-trial-information/ Advanced Cell Technology]- A biotechnology company which is currently running two clinical trials that utilise human embryonic stem cell derived retinal pigmented epithelial cells. These trials are examining the possibility of using these cells to treat stargardt's macular dystrophy and dry age-related macular degeneration<ref><pubmed>22281388</pubmed></ref>.

----

===LRP5 is required for vascular development in deeper layers of the retina===

<pubmed>20652025</pubmed>

{| width=800px
|-
|
The lipoprotein receptor-related protein 5 (LRP5) has a significant function in the development of retinal vasculature.<ref name="PMID20652025"><pubmed>20652025</pubmed></ref> Research has shown that mutations of the LRP5 causes loss of function, due to incomplete development of retinal vessel network, in both humans and mice. The authors investigated how mutations occur in the LRP5, which leads to abnormal development of the retinal vasculature. They have studied retinal endothelial cells in mutant mice in their study. Their results showed that in retina with mutated LRP5, endothelial cells in the retinal vasculature primarily produced cell clusters in the inner-plexiform layer instead of migrating into deeper layers of the retina to form normal retinal vasculature. The authors also discovered that there was a decrease in Slc38a5, which is a “a Müller cell-specific glutamine transporter”, in mice with mutated LRP5. Their results lead the authors to conclude that normal LRP5 is very important in the development of normal retinal vasculature due to their role in causing migration of retinal endothelial cells in the deeper layers of the retina. LRP5 is also important for retinal interneurons and Müller cells to function correctly.

|
[[File:Retina-cell-clusters.JPG|350px|thumbnail|'''Endothelial cells form thick clusters in the LRP5 mutant retina''']]
|}

-----------------

==Useful Links==

{{External Links}}

[http://www.youtube.com/watch?v=Xme8PA6xv-M Visualisation of eye development in the embryo]

[http://www.embryo.chronolab.com/sense.htm Embryonic Development of the eye]

==Glossary==

'''Accommodation''' - changing the focal length of the lens in order to focus on an object.

'''Downstream genes''' - genes that are activated by other "upstream genes".

'''Ectoderm''' - outermost layer of germ cells in an early embryo.

'''Endoderm''' - innermost layer of germ cells in an early embryo.

'''Glial cells''' - non-neuronal cells that provide structure and protection to neurons as well as producing myelin.

'''Inductive signaling''' - a process whereby the secretion of factors from one cell or tissue triggers a response in another.

'''Lens vesicle''' - the cavity of invaginated ectoderm from the optic placode that will form the lens.

'''Macula''' - a highly pigmented, oval-shaped area located near the centre of the retina. Important for visual acuity.

'''Mesenchyme''' - undifferentiated, loose connective tissue.

'''Mesoderm''' - middle layer of germ cells in an early embryo.

'''Mesothelium''' - the epithelial layer of the mesoderm.

'''Myelinisation''' - development of a myelin sheath around a nerve fibre.

'''Neural crest''' - a portion of the ectoderm situated next to the neural tube.

'''Neural groove''' - a large invagination on the dorsal surface of the embryo which will close off and form the neural tube.

'''Neural tube''' - hollow structure that results from the folding of the neural plate and eventually forms the central nervous system.

'''Neuroblastic layer''' - a layer of immature cells that differentiate to form either glial cells or neurons. The retina has two of these (an inner and outer).

'''Neuroectoderm''' - portion of the ectoderm that develops to form the central and peripheral nervous systems.

'''Optic chiasm''' - the point at which the optic nerves meet and cross over.

'''Optic cup''' - the structure that is formed after the optic vesicle folds in upon itself. This will form the retina.

'''Optic globe''' - a term that refers to the optic cup, lens vesicle and surrounding mesenchyme collectively.

'''Optic placode''' - area of thickened ectoderm that gives rise to the lens of the eye.

'''Optic stalk''' - a long, narrow cavity that will produce the optic nerve.

'''Optic vesicle''' - a cavity that buds off from the neural tube and gives rise to the optic cup.

'''Upstream genes''' - genes that activate one or more other "downstream genes".

'''Vascularise''' - to invade with blood vessels.

==Image Gallery==
<gallery>
Image:Eye_diagram_bandw.jpg‎ | Basic structure of the human eye.
Image:Stage14 sem2b-limb.jpg | A Stage 14 embryo showing the location of an otic placode.
Image:Stage 13 image 060.jpg | A cross section showing the organisation of the developing brain, the optic vesicle and the lens (optic) placode.
Image:Formation of the optic vesicle 1.jpg | Early formation of the optic vesicle from the neural groove.
Image:Formation of the optic vesicle 2.jpg | The optic vesicle at a later stage, showing the optic stalk.
Image:Formation of the optic nerve and chiasm 1.jpg | A recognisable brain and eye structure in later development.
Image:Formation of the optic cup 1.jpg | Mechanism of optic cup formation.
Image:Formation of the optic cup 2.jpg | Layers of the optic cup in retina development.
Image:Formation of the retina 1.jpg | Cross-section of the primitive retina showing cell types and layers.
Image:Formation of the retina 2.jpg | Cross-section of a developed retina showing cell types and layers.
Image:Formation of the lens 1.jpg | The importance of the optic cup in lens differentiation.
Image:Formation of the lens 2.jpg | The lens placode separates from the ectoderm and migrates into the mesoderm forming the lens vesicle.
Image:Formation of the choroid and sclera 1.jpg | The choroid and sclera derives from mesenchyme surrounding the optic cup.
Image:Formation of the eyelid 1.jpg | Small grooves in the ectoderm of the head - the precursors to an eyelid.
Image:Formation of the eyelid 2.jpg | The eye at an advanced stage of embryonic development. Note however, that the eyelids remain fused until much later.

</gallery>

==References==
<references/>

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--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

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{{2012Projects}}

2012 Group Project 1

2012-10-02T13:20:16Z

Z3254758: /* Iris */

[[File:Eye_collage_2.jpg|right|830px]]

=Vision Development=

==Introduction==

Eyes are an important sensory organ shared across many different species and allow organisms to gather useful visual information from their environment. The visual system uses light from the environment and processes this information in the brain for visual perception. The visual system is complex, and is made up of various structures that work together to form vision. Each of the structures in the eye have specific tasks which contribute to the visual system. Knowledge of how the eye develops extends as far back as Aristotle more than 2000 years ago, and current knowledge shows that most of the crucial events of eye development occur in the embryological stage. The eye is an interesting model for studying the development of tissues in organisms, as it consists of cells from several parts of the embryo including the head ectoderm, neural ectoderm and mesoderm. From its many origins the cells come together and differentiate to produce the complex organ that is the eye. During this period there are many examples of inductive signaling, as the tissues coordinate their development throughout this elegant process.

The main anatomical structures of the eye are as follows:
{|
|
* Cornea

* Sclera

* Choroid

* Iris

* Ciliary body

* Lens

* Anterior chamber

* Posterior chamber

* Retina

* Optic nerve

|[[File:eye_diagram_bandw.jpg|right|250px|thumb|Basic structure of the human eye.]]
|}
[[File:Eyediagramcolour1.JPG|550px]]

==Research History==

=== '''Brief Timeline of Historical Developments on the Eye and its Embryology''' ===

{| width=800px
|-bgcolor="CEDFF2"
| width=100px|'''Time'''
| width=700px|'''Discovery'''

|-bgcolor="F5FAFF"
| '''Ancient Egyptians'''
| First to document cataracts. It is described as being 'the white disease of the eye' or 'darkening of the pupil.' <ref>Edwards, D.D. (1996). Ophthalmology before Hippocrates. In the History of Ophthalmology, ed. D.M. Albert and D.D. Edwards. Cambridge, Mass.: Blackwell Science.</ref> The Egyptians had some knowledge of the eye, however it is not known how much of the anatomy of the eye was known in their era.

|-bgcolor="CEDFF2"
| '''535 BC'''

|
Ancient Greek philosopher Alcmaeon conducted dissection of humans for the first time in recorded history. This included dissection of the eye. However, not much is known about which anatomical features he discovered. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17.">Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17.</ref>

|-bgcolor="F5FAFF"
| '''384- 322 BC'''

| [[File:Aristotle-eye.jpg|200px|thumbnail|The eye according to Aristotle.<ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "> Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau </ref> Note the lens is missing, and there are three vessels drawn that was believed to transport fluid to and from the eye.<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
]]
Aristotle performed dissections of animal embryos.<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

When Aristotle described the embryo of a ten day old chicken, he wrote "The eyes about this time, if taken out, are larger than beans and black; if their skin is removed the fluid inside is white and cold, shining brightly in the light, but nothing solid." <ref name="Magnus, H. (1998). Ophthalmology of the ancients. In J. Hirschberg (Ed.), The History of Ophthalmology: The monographs, Vol. 4, Part 1 (F.C. Blodi, Trans.) Bonn: Wayenborgh.">Magnus, H. (1998). Ophthalmology of the ancients. In J. Hirschberg (Ed.), The History of Ophthalmology: The monographs, Vol. 4, Part 1 (F.C. Blodi, Trans.) Bonn: Wayenborgh.</ref>

Aristotle believed that the eyes started forming during early embryogenesis, however, he also believed that the eyes are the last organs to form completely, and he incorrectly thought that the eyes shrink in later embryonic development. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press.">Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press.</ref> .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"

| '''340 BC'''

| Lens is thought to have been discovered by Hippocrates, due to his descriptions of the contents of the internal eye There has been studies in chick development later on by followers of Hippocrates. They claimed that eyes were visible in early embryogenesis. .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
|-bgcolor="F5FAFF"
|'''25 BC - 50 AD'''

| [[File:Celsus-eye.jpg|150px|thumb|The eye according to Celsus. <ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "/>
Note the lens is placed in the centre of the eye, in the vitreous.<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> ]]

Aulus Cornelius Celsus wrote a Roman medical text called 'De Medicina' in which he wrote that the lens was the part of the eye from which vision originated. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.">Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.</ref> Celsus also incorrectly drew the lens in the center of the globe in his diagram of the eye. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

|-bgcolor="CEDFF2"
| '''23-79 AD '''
|
Pliny the Elder said that the eye is the last of the organs to develop in the womb <ref name="Magnus, H. (1998). Ophthalmology of the ancients. In J. Hirschberg (Ed.), The History of Ophthalmology: The monographs, Vol. 4, Part 1 (F.C. Blodi, Trans.) Bonn: Wayenborgh."/>
|-bgcolor="F5FAFF"
| '''98-117 AD'''

| [[File:Rufus-eye.jpg|150px|thumb|The eye according to Rufus of Ephesus. <ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "/>
Note the lens is placed in the correct position, behind the iris of the eye <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> ]]

Rufus of Ephesus identified the lens as being located in the anterior part of the eye, close to the pupil. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

His diagram illustrates that he knew the correct position of the lens as being directly behind the iris, in the anterior part of the eye, and not in the centre as was previously depicted by others before him.

|-bgcolor="CEDFF2"
| '''130-200 AD'''

| [[File:Galen-eye1.jpg|150px|thumb|The eye according to Galen. <ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "/> ]]

Claudius Galen practised medicine in Rome. He wrote:

"1. Within the eye the principal orgran of sensation is the crystalline lens.

2. The sensation potential comes from the brain and is conducted via the optic nerves.

3. All other parts of the eyeball are supporting structures." <ref> Hirschberge, J. (1982). Antiquity, Vol. X in the History of Ophthalmology (F.C. Blodi, Trans.) Bonn: Wayenborgh. pp. 280 </ref>

Galen thought that the lens was produced from the vitreous. He also believed that the retina’s function was to give nourishment to the lens and vitreous, and to carry visual information to the brain from the lens. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

|-bgcolor="F5FAFF"

| '''1514-1564'''

| Andreas Vesalius published his anatomy book "De Humani Corporis Fabrica in 1543. He had the misconception that the lens was located in the centre of the eyeball. .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> He also wrote that the lens functioned "like a convex lens made of glass" <ref name="Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.">Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.</ref> pp. 48
|-bgcolor="CEDFF2"
| '''1535-1606'''

| Georg Bartisch correctly drew a diagram of the lens placed behind the iris in his book 'Ophthalmodouleia: das ist Augendienst'. <ref name="Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>
|-bgcolor="F5FAFF"

| '''1537-1619'''

| Fallopio Hieronymus Fabricius ab Aquapendente studied anatomy and embryology. He studied chicken embryos, and thought that chalazae (which comes from egg white) gives rise to the eyes. He also drew the lens directly behind the iris in a diagram in is book 'Tractatus de Oculo Visuque Organo. <ref name="Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

|-bgcolor="CEDFF2"
| '''1583'''

| Felix Platter published his book 'De corporis Humani Structura et Usu, after he performed dissections of human bodies. He believed that the retina is the primary visual organ in the eye. .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="F5FAFF"
| '''1619'''
| Scheiner is given credit to be the first person to correctly draw the diagram of the anatomy of the eye. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
|-bgcolor="CEDFF2"
| '''1672'''
| Marcello Malpighi described the embryonic development of the chicken. He drew many detailed diagrams of the chick eye. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1665'''
| Nicolaus Steno identified the choroid fissure in his study of a developing embryo of a chicken. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="CEDFF2"
| '''1754'''

| Albrecht von Haller studied the embryology of the eye. With help from his student Johann Gottfried Zinn, he contributed to the understanding of the development of the ciliary body, ciliary zonule, and their relationship with the lens and vitreous. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1817'''

| Christian Pander discovered the three embryonic germ layers, which he wrote about in his book. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/> Pander was the first to think of 'the optic vesicles as lateral evaginations' of the 'prosencephalon'; however, he was incorrect about the details regarding how 'the eye develops from these evaginations'. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="CEDFF2"
| '''1828-1837'''

| Karl Ernst von Baer studied embryology. He discovered that the optic vesicles were 'outgrowths of the embryonic forebrain' <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> which he believed was caused by pressure from fluids in the central nervous system. Von Baer also believed that the optic vesicle opens to form the pupil, and that fluid in the optic vesicle coagulates to form the vitreous body and lens. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1830'''

| Emil Huschke discovered that the lens forms from the invagination of the surface ectoderm. He concluded that the lens hence does not form ‘from the fluid of the optic vesicle’ <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> as previously thought.
|-bgcolor="CEDFF2"
| '''1832'''

| Emil Huschke wrote in his manuscript ‘Ueber die erste Entwinkenlung des Auges und die damit zusammenhängende Cyklopie’ that the lens capsule forms from the outer surface ectoderm, which detaches and moves back inward, which is later enclosed again by several membranes, such as by the cornea. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

Huschke also described how the optic cup and choroid fissure forms. He discovered that the optic vesicles are produced from the two-layered optic cup. However, he incorrectly described the destiny of the ‘individual optic cup layers’. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

|-bgcolor="F5FAFF"
| '''1838'''
| Matthias Jakob Schleiden and Theodor Schwann formulated the ‘cell theory’: “All living things are formed from cells, the cell is the smallest unit of life, and cells arise from pre-existing cells.” <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
|-bgcolor="CEDFF2"
| '''1839'''

| Theodor Schwann contributed a better understanding of the development of the lens through studying the foetus of a pig, which he wrote about in his book ‘Mikroskopische Untersuchungen Über Die Uebereinstimmung in Der Struktur Und Dem Wachsthum Der Thiere Und Pflanzen’. He wrote that the lens is made of ‘concentric layers’ of fibres which proceeds from an anterior to posterior direction. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1842'''
| Robert Remak gave the current names to the three embryonic germ layers: ectoderm, mesoderm and endoderm. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"
| '''1843'''
| Wilhelm Werneck published his book ‘Beiträge zur Gewebelehre des Kristallkörpers’. He wrote that the contents inside of the lens is not made of fluids, as was previously believed. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/> Werneck also discovered that the fibers of the lens continues to grow from the outside to the centre during embryogenesis. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

|-bgcolor="F5FAFF"
| '''1855'''

| Robert Remak wrote his book ‘Untersuchungen über die Entwickelung der Wirbelthiere’. He wrote about what he discovered in his studies of the development of the eye in the embryos of chickens, frogs, and rabbits. He wrote very descriptively about the embryology of lens formation, amongst other topics. He discovered that the ectoderm gives rise to the lens placode. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

|-bgcolor="CEDFF2"
| '''1858'''
| Henry Gray published his book 'Anatomy, Descriptive and Surgical'. He had also previously studied the embryonic development of the optic nerve and retina of chickens.
|-bgcolor="F5FAFF"
| '''1877'''
| Paul Leonhard Kessler wrote about the embryonic development of the lens in mice in his book ‘Zur Entwickelung des Auges der Wirbelthiere. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"
| '''1891'''
| Vincenzo Colucci studied newts and discovered their ability to regenerate the lens.<ref> Tsonis, P. A. (2001). Regeneration of the Vertebrate Lens and Other Eye Structures. eLS. (Online Publication). DOI: 10.1038/npg.els.0001102 </ref>
|-bgcolor="F5FAFF"
| '''1892'''
| Dr. Oscar Hertwig published his book ‘Text-Book of the Embryology of Man and Mammals. <ref> Hertwig, O. Text-book of the embryology of man and mammals. S. Sonnenschein 1901. (Translated from the 3d German ed. by Edward L. Mark.) </ref> It contains a very detailed description of the development of the eye, according to the findings at that time. [http://embryology.med.unsw.edu.au/embryology/index.php?title=Book_-_Text-Book_of_the_Embryology_of_Man_and_Mammals_16-2#The_Development_of_the_Eye]
|-bgcolor="CEDFF2"
| '''1895'''
| Gustav Wolff also independently studied newts and discovered their ability to regenerate the lens. .<ref> Tsonis, P. A. (2001). Regeneration of the Vertebrate Lens and Other Eye Structures. eLS. (Online Publication). DOI: 10.1038/npg.els.0001102 </ref>

|-bgcolor="F5FAFF"

| '''1900'''
| Carl Rabl published his book ‘Uber den Bau und die Entwicklung der Linse’. He wrote about the development of the lens in mammals, fish, birds, reptiles, and amphibians. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"
| '''1901'''
| Hans Spemann published his findings from his experimental studies about the formation of the lens in the frog. He found that the optic cup needed to be in contact with the ectoderm for normal development of the eye. <ref> Spemann, H. (1901). Über Correlationen in der Entwicklung des Auges. Verhand. Anat. Ges. 15: 61-79. </ref> <ref> Saha, M. (1991). Spemann seen through a lens. In Gilbert, S. F. (ed.). A Conceptual History of Modern Embryology. Plenum Press, NY. pp. 91-108.</ref>
|-bgcolor="F5FAFF"
| '''1906'''
| Brown ‘s book “The Embryology Anatomy and Histology of the Eye” was published. It contained detailed descriptions of the embryonic development of the eye according to the knowledge current at that time, mainly based on observations from embryos of rabbits and chickens. <ref> Brown, E.J. (1906). The Embryology Anatomy and Histology of the Eye. Chicago: Hazlitt & Walker. 1906 </ref>

|-bgcolor="CEDFF2"
| '''1907'''

| John Clement Heisler published his book ‘A Text-book of embryology’. It contains a chapter detailing the embryonic development of the eye, according to the knowledge current at that time. The book’s copyright has expired, so it can be viewed free online: [http://archive.org/details/atextbookembryo01heisgoog]

Julius Kollman also published his book 'Atlas of the Development of Man'. It contained very detailed description and illustrations showing the embryonic development of the human according to the knowledge current at that time. His illustrations were reused by many others after his time and built upon for further refined understanding of the embryology of the human.

Here are examples of Julius Kollman's excellent illustrations showing eye development in various stages:

'''Formation of Primary Optic Vesicle:'''
<gallery>
File:Kollmann691.jpg|The blue part at the bottom is the endoderm. The pink middle layer is the mesoderm. The top yellow layer is the ectoderm. The fold labelled as 'augenfeld' is the place where the optic vesicle will form.
File:Kollmann692.jpg|The eye area (augenfeld) is a bowl shaped bulge still located on the side walls.
File:Kollmann693.jpg| The neural tube is shown after removal of all of the ectoderm and ventral organs, such as heart, gut tube, etc. The primary optic vesicle forms a slightly flattened hollow protrusion on the forebrain.
File:Kollmann694.jpg|The lateral surface of the primary optic vesicle is slightly depressed, showing the first sign of the emergence of the secondary optic vesicle
</gallery>

'''Development of Lens:'''

<gallery>
File:Kollmann695.jpg|The bulging lateral wall of the primary optic vesicle is covered by a fairly well demarcated lens plate, a direct continuation of the ectoderm. Between the optic vesicle and the lens pit are some flattened spindle-shaped cells. In the adjoining mesoderm are cross-sections of capillaries.
File:Kollmann697.jpg|The lens still hangs together with the ectoderm. The primary eye vesicle is indented with respect to the lens. Between the lens and the lateral plate of the optic vesicle is a narrow space, which allows area to further develop later.
File:Kollmann698.jpg|4th Week of development. The internal organisation shows the secondary optic vesicle. A: The rear wall of lens is noticeable and is enveloped by mesoderm. B: The edges of the lens pit is already grown and the lens vesicles are formed, which is still related to the remaining ectoderm.
File:Kollmann699.jpg|The lens has now cut off from the ectoderm, but is still very superficial. Between it and the lateral lamina of the optic cup, there is a considerable space. The eye stalk has become longer and is enclosed together with the optic cup and lens of the mesoderm. The cornea, sclera and choroid make gradual development.
</gallery>

|-bgcolor="F5FAFF"

| '''1921'''
| Bailey and Miller published their textbook “Text-Book of Embryology “. <ref> Bailey, F.R. and Miller, A.M. (1921). Text-Book of Embryology. New York: William Wood and Co. (Note- This book is only at an early edited stage)</ref> It contains detailed description of the development of the embryonic eye according to the knowledge current at that time. [http://embryology.med.unsw.edu.au/embryology/index.php?title=Book_-_Text-Book_of_Embryology_18]

|-bgcolor="CEDFF2"
| '''1925'''

| Mann published his research article, in which he gives a detailed account of the development of the human iris. He divided the development of the iris into four stages: weeks 4-7 (before the ectodermal iris forms or before the anterior chamber forms); weeks 7-11 (anterior chamber appears, and mesodermal iris forms); weeks 11-12 (ectodermal iris forms); 3-8 months (muscles of the pupil forms from ectodermal iris, and the central portion of the mesodermal iris atrophies to make the pupil clear). <ref name="PMID18168466"><pubmed>18168466</pubmed></ref>
O Leser also published an article detailing the development of extraocular muscles in mammals he studied. <ref name="PMID18168498"><pubmed>18168498</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1939'''
| Holtfreter <ref> Holtfreter, J. (1939). Gewebeaffinitat, ein Mittel der embryonalen
Formbildung. Arch. Exp. Zellforsch. 23, 169-209. </ref> studied amphibians and observed that that the development of the eye stops at the ‘optic vesicle stage’ if there is no contact ‘with the epidermis and neural crest driven mesenchyme’. <ref name=”PMID11023863”><pubmed>11023863</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1955'''
| Barber published his book ‘Embryology of the human eye’. <ref> Barber AN: Embryology of the human eye. St. Louis. CV Mosby 1955</ref> In contains detailed descriptions of the embryological development of the human eye according to the knowledge current at that time. It contains many photographs of the eye at different stages of development.

|-bgcolor="F5FAFF"
| '''1957'''
| Coulombre studied a chicken embryo to find the role of intraocular pressure in the development of the chick’s eye, especially in regards to its control of the size of the eye structures. <ref name="PMID13469954"><pubmed>13469954</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1958'''
| Coulombre studied the development of the cornea and how it develops its transparency. <ref name="PMID13563560"><pubmed>13563560</pubmed></ref> He also studied the development of corneal curvature. <ref name="PMID 13519969"><pubmed> 13519969</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1962'''
| Coulombre studied the development of the conjunctival papillae and scleral ossicles. <ref name="PMID 14023393"><pubmed> 14023393</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1963'''
| Coulombre studied the development of lens fibers and their orientation. <ref name="PMID14077035"><pubmed>14077035</pubmed></ref> He also studied the development of pigmented epithelium. <ref name="PMID14023394"><pubmed>14023394</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1964'''

| Coulombre further studied the development of the lens to determine the role of the lens in eye growth. <ref name="PMID14189921"><pubmed>14189921</pubmed></ref> He also studied the role of thyroid in the development of the cornea and the development of corneal transparency. <ref name="PMID14211912"><pubmed>14211912</pubmed></ref> Mann also published his work called ‘The development of the human eye’, which contains detailed description of the embryonic development of the eye according to current knowledge at that time. <ref> Mann I. The development of the human eye. New York: Grune and Stratton 1964</ref>

|-bgcolor="CEDFF2"
| '''1965'''
| Coulombre published his findings regarding the regeneration of the neural retina from pigmented epithelium in the embryo of chickens. <ref name="PMID5833111"><pubmed>5833111</pubmed></ref> Smelser also published his findings on the embryological development and morphology of the lens. <ref name="PMID14340157"><pubmed>14340157</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1966'''

| Formation of the face and orbit occurs from the differentiation of neural crest cells. <ref name="PMID5969670"><pubmed>5969670</pubmed></ref> O’Rahilly also published findings of the development of the eye in the early stages of human embryos. <ref> O'Rahilly, R. 1966 The early development of the eye in staged human embryos. Contr. Embry. Carnegie Inst., Wash., 38: 1–42</ref>

|-bgcolor="CEDFF2"
| '''1968'''
| Findings of the postnatal development of the retina of rats was published. <ref name="PMID5640327"><pubmed>5640327</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1969'''

| Mann again published his work called ‘The development of the human eye’. He stated that that the lens in humans forms completely from the ectoderm. <ref name=”Mann I. The Development of the Human Eye. New York, USA: Grune & Stratton, Inc; 1969”> Mann I. The Development of the Human Eye. New York, USA: Grune & Stratton, Inc; 1969</ref> Coulombre also studied the development of the lens, and took note of its size, shape and orientation throughout its developmental stages. <ref name="PMID 5772716"><pubmed> 5772716</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1970'''
| Coulombre again further studied the regeneration of the neural retina from pigmented epithelium of embryos of chickens. <ref name="PMID 5472476"><pubmed> 5472476</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1971'''

| Coulombre further studied the development of the lens. This time he focused on analysing the histological mechanisms in the reconstitution of the lens from implanted lens epithelium. <ref name="PMID 4925671"><pubmed> 4925671</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1973'''
| A research article was published, detailing the embryonic development of the retina of humans. <ref name="PMID 6650859"><pubmed> 6650859</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1976'''

| Geeraets published his observations of the closure of the embryonic optic fissure in golden hamsters, using the electron microscope. <ref name="PMID 1266776"><pubmed> 1266776</pubmed></ref> Kornneef also published an article based on his studies of the development of connective tissue in the human orbit. <ref name="PMID 1020699"><pubmed> 1020699</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1981'''
| A research article was published detailing how myelin forms in the optic nerve of humans. <ref name="PMID 7224936"><pubmed> 7224936</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1983'''
| O’Rahilly’s further research developments was published, reporting the timing and sequence of events in the development of the embryonic human eye. <ref name="PMID 6650859"><pubmed> 6650859</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1990'''

| Van Driell et al. <ref>Driell, D. Van; Provis, J.M.; Billson, F.A.: Early differentiation of ganglion, amacrine, bipolar and Muller cells in the developing fovea of the human retina. J. Comp. Neurol. 291: 203-219.</ref> studied the manner in which amacrine, bipolar, retinal ganglion cells, and Muller cells differentiate in the developing fovea of the retina of a 15-week old human foetus. <ref name="PMID1628748"><pubmed>1628748</pubmed></ref> Tripathy also published an article providing evidence that the lacrimal glands in humans originates from the neuroectoderm. <ref name="PMID2406219"><pubmed>2406219</pubmed></ref>

|}

==Development, Structure and Function of Ocular Components==

The eye itself is formed from several components; notably the optic placode of the head ectoderm, the optic vesicle from the neural tube, and mesenchyme from the mesoderm and neural crest cells. The optic placode contributes the lens to the eye, the optic vesicle gives rise to layers of the retina, while the mesenchyme will produce the ciliary body, iris, choroid and sclera.<ref>http://www.vetmed.vt.edu/education/curriculum/vm8054/eye/EMBYEYE.HTM</ref> Cells from the neural tube will also produce the optic nerve, which receives nerve impulses from the retina of the eye. Eyes initially form as laterally paired structures and migrate medially in the human embryo. In other animals such as birds and lizards, the eyes do not migrate and develop laterally on the head. The optic placodes become prominent on the surface of the embryo at approximately Stage 14 of development.

[[File:Stage14 sem2b-limb.jpg|200px|thumb|left|A Stage 14 embryo showing the location of an otic placode.<ref name="http://embryology.med.unsw.edu.au/embryology/index.php?title=ANAT2341_Lab_6_-_Early_Embryo">http://embryology.med.unsw.edu.au/embryology/index.php?title=ANAT2341_Lab_6_-_Early_Embryo</ref>]] [[File:Stage 13 image 060.jpg|400px|thumb|center|A cross section showing the organisation of the developing brain, the optic vesicle and the lens (optic) placode.<ref name="http://embryology.med.unsw.edu.au/embryology/index.php?title=ANAT2341_Lab_6_-_Early_Embryo"/>]]

===Optic Nerve===

The optic nerve consists of nerve fibres that transmit information from the retinal photoreceptor cells to the brain. The optic nerve is formed from the optic stalk, which develops as the optic vesicle migrates from its origin in the neural tube to its destination - the surface ectoderm - where it will fuse with the optic placode (also known as the lens placode, which will contribute the lens to the eye).<ref name="PMID11687490"><pubmed>11687490</pubmed></ref>

[[File:Formation of the optic vesicle 1.jpg|400px|thumb|left|Fig. 1: Early formation of the optic vesicle from the neural groove.]] [[File:Formation of the optic vesicle 2.jpg|400px|thumb|center|Fig. 2: The optic vesicle at a later stage, showing the optic stalk.]]

As can be seen in Figure 1 above, the optic vesicle forms from the neural tube. However, note that the neural tube has not yet closed, and is still the neural groove at this point. Figure 2 then shows the optic vesicle at slightly later stage in the same simplified cross-section of the embryo, as it migrates from the neural tube to the surface ectoderm. Note the presence of the optic stalk which links the optic vesicle to the neural tube. Later in development, this primitive structure will become the optic nerve, which will link the eye to the brain.

The nerve fibres themselves will initially originate from the retinal ganglion cells in the eye during week 6.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008">Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008</ref> After two weeks, these fibers will have grown along the inner wall of the optic stalk and have reached the brain. They grow both in length and width, with the nerve fibres filling the hollow optic stalk to form the solid optic nerve. More than one million nerve fibers will eventually make up the optic nerve, along with glial cells which arise from the inner wall of the optic stalk itself.<ref><pubmed>1451666</pubmed></ref> Myelinisation of the optic nerve begins much later in development at around 7 months, beginning at the optic chiasm and moving towards the eye.<ref><pubmed>7224936</pubmed></ref> The optic chiasm forms just before the nerves reach the brain, and is where half the nerve fibres from each eye will cross over to the opposite side of the brain. This is demonstrated in Figure 3. Note the crossing over of the optic nerves just before they enter the brain, at the optic chiasm. This organisation is now much more familiar, with the eyes near the ectoderm and the optic nerve leading through the mesoderm to the brain buried deep in the embryo.

[[File:Formation of the optic nerve and chiasm 1.jpg|400px|thumb|center|Fig. 3: A recognisable brain and eye structure in later development.]]

===Retina===

The retinal component of the eye is formed when the optic vesicle folds in upon itself, forming the optic cup (see Figure 4). In doing so it creates two layers - an inner wall and an outer wall of the optic cup (Figure 5). These two layers of the optic cup will give rise to the two layers of the retina - the inner neural retina, and the outer pigmented epithelium.<ref name="PMID11687490"/> Note the existence of the space between the two layers of the retina. This is known as the intraretinal space and disappears by the 7th week of development, however the two layers never completely fuse and can become separated as a result of physical trauma to the head - leading to a detached retina and loss of vision.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/>

The inner wall of the optic cup, which will give rise to the neural retina, consists of a layer of pseudostratified cells (see Figure 6) that later differentiate into rod, cone, bipolar, ganglion, horizontal, amacrine and glial cells of the retina (Figure 7).<ref name="PMID18168748"><pubmed>18168748</pubmed></ref> The outer wall of the optic cup consists of a layer of cuboidal cells that contain melanin - the light absorbing pigment. The function of this layer is to absorb light and prevent internal reflection of light within the eye, which would impair our ability to form distinct images. Interestingly, in some animals such as cats, this layer actually reflects light intentionally to increase the amount of light available to the eye in low-light conditions. This is why cats seem to have eyes that glow in the dark.<ref>http://dialspace.dial.pipex.com/agarman/bco/fact4.htm</ref>

[[File:Formation of the optic cup 1.jpg|400px|thumb|left|Fig. 4: Mechanism of optic cup formation.]] [[File:Formation of the optic cup 2.jpg|400px|thumb|center|Fig. 5: Layers of the optic cup in retina development.]]

The inner wall itself is divided into two components - the inner neuroblastic layer and the outer neuroblastic layer (see Figure 6). The outer neuroblastic layer forms the rod and cone cells while the inner neuroblastic layer forms the remaining cell types found in the retina - the bipolar, ganglion, horizontal, amacrine and glial cells (Figure 7).<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/> The organisation of the retina is interesting in that incoming light passes through several layers of these neural retina cells before it is detected by rod and cone cells at the back of the retina, and then nerve signals are passed back through the layers of neural retina cells that the light just passed through moments before - a seemingly strange design that the eye does not share with man-made light-capturing devices such as a camera (imagine putting the wires in front of the image sensor!).

Differentiation of the neuroblastic layers into neural retina cells occurs in a pattern both within the layers and across the retina. Cells differentiate from the inner neuroblastic layer to the outer neuroblastic layer, and differentiate from the central retina to the peripheral retina.<ref name="PMID18168748"/> The macula is first identifiable in week 22 when ganglion cells start to form multiple rows, and the primitive fovea begins to form at approximately the same time as a depression in the macula.<ref><pubmed>6462623</pubmed></ref> It is not until 15-45 months after birth that this area becomes exclusively populated by cone cells and becomes the fovea centralis - the area of the retina with the highest visual acuity.

[[File:Formation of the retina 1.jpg|400px|thumb|left|Fig. 6: Cross-section of the primitive retina showing cell types and layers.]] [[File:Formation of the retina 2.jpg|400px|thumb|center|Fig. 7:Cross-section of a developed retina showing cell types and layers.]]

===Ciliary Body===

The ciliary body consists of ciliary processes and three portions of fibres that constitute the ciliary muscles. It functions to maintain normal eye physiology as well as playing a direct role in accommodation.

During development, the ciliary processes form slightly posterior to the iris, developing from part of the anterior rim of the optic cup. It is thought that the folded structure of the ciliary processes is brought about by intraocular pressure and specific signalling pathways.<ref name="PMID16959249"><pubmed>16959249</pubmed></ref> While the ciliary muscles and the endothelial cells of the ciliary blood vessels are chiefly formed by mesenchymal cells<ref><pubmed>16249499</pubmed></ref>, the neural crest and neuroectoderm also contribute to their development.<ref><pubmed>12127103</pubmed></ref> The normal development of the ciliary body is dependent on the correct expression of bone morphogenetic protein (BMP)-4, which is a member of the transforming growth factor-β superfamily.<ref><pubmed>1222340</pubmed></ref> Napier and Kidson (2007) summarised numerous genes that have been associated with ciliary body development, however their direct roles have not been well documented.<ref name="PMID16959249"/>

===Iris===

The iris is a thin layer that develops at the end of the third month of development and is derived from the anterior rim of the optic cup. The stroma of the iris develops from cells of neural crest cell origin.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/> The muscles that are responsible for the dilation and constriction of the pupil (dilator pupillae and sphincter pupillae muscles) form from the neuroectoderm of the optic cup. These cells are initially epithelial cells that then transform into smooth muscle cells. <ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"></ref>. The invagination of the optic vesicle which creates the optic cup, also causes the formation of the optic cup lip. This is the region of the where the epithelium doubles back, separating the outer pigmented layer and the inner nonpigmented layer. This is the edge of the iris that borders on the pupil<ref><pubmed> Retinal and anterior eye compartments derive from a common progenitor pool in the avian optic cup</pubmed></ref>.

The final colour of the iris is not evident until the postnatal period. It is determined by a number of genes including IRF4, SLC24A4 and MATP<ref><pubmed>19710684</pubmed></ref>. Other features such as crypt frequency, furrow contractions, presence of peripupillary pigmented ring, and number of nevi also become evident during development<ref><pubmed>21835309</pubmed></ref>.

Mutations in Pax6 have been shown to cause partial or complete loss of the iris <ref><pubmed>12386935</pubmed></ref>.

===Cornea===

The cornea is the transparent, avascular, most anterior portion of the eye. It is responsible for conducting light into the eye and focusing it on to the retina, as well as maintaining the rigidity of the eyeball. It consists of 5 layers- the epithelium, Bowman’s layer, stroma, Descemet’s membrane and the endothelium.

The epithelium and endothelium of the cornea first appear during the 5th week of gestation. The epithelium of the external surface of the cornea is derived from surface ectoderm, while the mesenchyme is derived from the mesoderm<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"/>. The endothelium is a two-cell cuboidal layer which is made up of differentiated neural crest cells that were initially from the optic cup. By week 8 the endothelial cells begin to secrete a basement membrance which later forms Descemet’s membrane<ref><pubmed>6511224</pubmed></ref>. At approximately 16 weeks gestation the Bowman’s membrane begins to form from the thickening of the stroma that is located under the corneal epithelium<ref>Riordan-Eva P, Whitcher JP. Vaughn and Asbury's General Ophthalmology, Lange Medical Books/McGraw Hill. 2004:25–27</ref>. During the third month glycosaminoglycans secreted by fibroblasts form the ground substance of the cornea, with collagen fibrils and keratan sulphate also appearing around this time. Shortly after this tight junctions form between the endothelial cells<ref><pubmed>19481138</pubmed></ref>. Fibroblast growth factor causes the epithelial cells to proliferate<pubmed><ref>20105280</pubmed></ref>.

Towards the end of the gestational period the cornea becomes larger due to the production of aqueous humor<ref>Yanoff M, Duker JS. Ophthalmology. Mosby; St. Louis, MO: 2004</ref>. The final transparent structure develops because hyaluronidase removes hyaluronic acid, thyroxine causes dehydration of the stroma, and the entire structure becomes avascular<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/>. Numerous genes have been implicated in the development of the cornea, these include, but are not limited to, PAX6, PITX2, FOXC1, MAF, TMEM114, SOX2, OTX2 and BMP4<ref><pubmed>18637741</pubmed></ref>.

===Lens===

The lens has its origin from the optic placode, which develops on the ectodermic surface of the embryo and migrates both medially and inwards into the embryo. The lens allows accommodation of the eye, and adjusts its thickness in order to focus on near or far objects. The study of lens development was one of the first to highlight the importance of inductive signaling in development, with Spemann's pioneering work at the start of the 20th century, finding that the absence of retinal development resulted in the absence of lens formation.<ref name="PMID11687490"/> Indeed, it has been consistently shown that the interaction of the migrating optic vesicle with the surface ectoderm of the head is vital in producing differentiation of the lens.<ref name="PMID15558475"><pubmed>15558475</pubmed></ref> The mechanism of interaction is complex but basically involves upstream genes switching on downstream genes, with the genes eventually producing specialised proteins which constitute the lens. The whole process starts with the signaling molecules from the optic cup initiating a thickening of the surface ectoderm of the head (Figure 8). It is thought that this region of specific ectoderm is responsive to the signaling molecules, as lens formation is incomplete or absent when ectoderm from the lateral portion of the embryo (i.e. non-head ectoderm) is exposed to the same inductive signaling processes.<ref name="PMID9216064"><pubmed>9216064</pubmed></ref> Pax6 has been shown to be one of the major genes required for differentiation of the lens, which in turn switches on transcriptional genes such as Sox 1, 2 and 3 among others - producing water-soluble proteins called crystallins - responsible for giving the lens its transparency and refractive properties.<ref name="PMID9609835"><pubmed>9609835</pubmed></ref>

[[File:Formation of the lens 1.jpg|400px|thumb|left|Fig. 8: The importance of the optic cup in lens differentiation.]] [[File:Formation of the lens 2.jpg|400px|thumb|center|Fig. 9: The lens placode separates from the ectoderm and migrates into the mesoderm forming the lens vesicle.]]

The lens placode invaginates from the head ectoderm and migrates into the mesoderm (Figure 9). Once this structure (now known as the lens vesicle) is in place opposite the optic cup, the combined structure is referred to as the optic globe and resembles a recognisable eye structure. The lens continues to differentiate further, as mentioned above, through the formation of crystallin proteins, which give the lens its unique properties and allows for the fine control over the degree of refraction that takes place.

===Aqueous Chambers===

There are both anterior and posterior aqueous chambers of the eye which contain aqueous humour. A space develops in the mesenchyme situated between the lens and cornea to form the anterior aqueous chamber. The mesenchyme located superficially to this chamber forms the mesothelium as well as the transparent portion of the cornea.

The posterior chamber develops from a similar space in the mesenchyme, however it is located between the iris and the lens. The anterior and posterior chambers are able to communicate with one another once the papillary membrane vanishes and the pupil is formed. This channel is known as the scleral venous sinus.<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011">Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011</ref>

Contained within the aqueous chambers is aqueous humor. The production of aqueous humor is dependant on the development of the ciliary body. It is produced in the ciliary processes and it’s production is a metabolic process driven by the delivery of oxygen and the removal of wastes via the ciliary circulation<ref><pubmed>20801226</pubmed><ref>.

===Cornea===

The cornea is the transparent, avascular, most anterior portion of the eye. It is responsible for conducting light into the eye and focusing it on to the retina, as well as maintaining the rigidity of the eyeball. It consists of 5 layers- the epithelium, Bowman’s layer, stroma, Descemet’s membrane and the endothelium.

The epithelium and endothelium of the cornea first appear during the 5th week of gestation. The epithelium of the external surface of the cornea is derived from surface ectoderm, while the mesenchyme is derived from the mesoderm<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"/>. The endothelium is a two-cell cuboidal layer which is made up of differentiated neural crest cells that were initially from the optic cup. By week 8 the endothelial cells begin to secrete a basement membrance which later forms Descemet’s membrane<ref><pubmed>6511224</pubmed></ref>. At approximately 16 weeks gestation the Bowman’s membrane begins to form from the thickening of the stroma that is located under the corneal epithelium<ref>Riordan-Eva P, Whitcher JP. Vaughn and Asbury's General Ophthalmology, Lange Medical Books/McGraw Hill. 2004:25–27</ref>. During the third month glycosaminoglycans secreted by fibroblasts form the ground substance of the cornea, with collagen fibrils and keratan sulphate also appearing around this time. Shortly after this tight junctions form between the endothelial cells<ref><pubmed>19481138</pubmed></ref>. Towards the end of the gestational period the cornea becomes larger due to the production of aqueous humor<ref>Yanoff M, Duker JS. Ophthalmology. Mosby; St. Louis, MO: 2004</ref>. The final transparent structure develops because hyaluronidase removes hyaluronic acid, thyroxine causes dehydration of the stroma, and the entire structure becomes avascular<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/>. Numerous genes have been implicated in the development of the cornea, these include, but are not limited to, PAX6, PITX2, FOXC1, MAF, TMEM114, SOX2, OTX2 and BMP4<ref><pubmed>18637741</pubmed></ref>.

===Choroid and Sclera===

The choroid and sclera are adjacent layers that surround the eye and act to vascularise and protect the eye respectively. They are formed from neural crest and mesoderm-derived mesenchyme which condenses around the optic cup and lens vesicle between weeks 5 and 7 of development to form a primitive eyeball structure known as the optic globe.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/> Blood vessels first start to appear in the choroid layer at approximately week 15, and arteries and veins can be distinguished by week 23.<ref>Development of the Choroid and Related Structures, K. Sellheyer, Eye (1990) 4, 255-261</ref> Inductive processes are thought to play a vital role during formation of the choroid and sclera; with the retinal pigmented epithelium inducing differentiation of the surrounding mesenchyme while at the same time the neural crest-derived mesenchyme contributing components to the retinal pigmented epithelium such as melanocytes.<ref name="PMID1628748"/> In addition to having functional roles themselves, the primitive choroid and sclera also contribute components to the developing ciliary body and cornea (Figure 10). In the adult eye, the choroid is continuous with the ciliary body and the sclera with the cornea.

[[File:Formation of the choroid and sclera 1.jpg|400px|thumb|center|Fig. 10: The choroid and sclera derives from mesenchyme surrounding the optic cup.]]

===Eyelids===

The eyelids are ectodermal and mesodermal in origin and are an extension of the skin which covers and protects the eye. Eyelid formation can be first noted during week 5 when small grooves develop in the surface ectoderm (Figure 11).<ref><pubmed>7364662</pubmed></ref> These small grooves deepen and extend into the mesoderm and the primitive eyelid structures grow towards one another, eventually fusing together during week 8.<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"/> It is not until week 26-28 that the eyelids will separate again. The ectoderm reflects over the developing cornea to form the conjunctival sac, a space that is filled by secretions from the lacrimal gland in order to allow smooth motions of the eyelid over the eye and also to clean the cornea and prevent accumulation of particles on the eye that may disrupt vision. By the time the eyelids separate, the eye has all its major components present (Figure 12), and further development consists mainly of growth and vascularisation.

[[File:Formation of the eyelid 1.jpg|400px|thumb|left|Fig.11: Small grooves in the ectoderm of the head - the precursors to an eyelid.]] [[File:Formation of the eyelid 2.jpg|400px|thumb|center|Fig. 12: The eye at an advanced stage of embryonic development. Note however, that the eyelids remain fused until much later.]]

===Lacrimal Glands===

Lacrimal glands initially develop from budding of the conjunctival epithelium near the superolateral portion of the eye. The mesenchymal cells that surround these buds are of neural crest origin, and the budding continues until the mature gland is formed.<ref><pubmed> 9882499</pubmed></ref> These glands are responsible for the production of tears however they do not start to function until 1-3 months after birth.

==Current Research==

*more info will be added soon!!

===GABA Maintains the Proliferation of Progenitors and Non-Pigmented Ciliary Epithelium===

<pubmed>22590629</pubmed>

{| width=800px
|-
| width=450px|
| width=350px|

|-
| GABA is an ‘inhibitory neurotransmitter’ in the central nervous system of adults. <ref name="PMID22590629"><pubmed>22590629</pubmed></ref> It is responsible for controlling proliferation of stem cells and progenitor cells. The authors of this article <ref name="PMID22590629"/> was interested to find the effects of GABA on proliferation of progenitor cells and non-pigmented ciliary epithelial cells (NPE) in the retina. Their study focused on progenitor cells and non-pigmented epithelium of the ciliary body in chickens. Non-pigmented epithelial cells in chickens arise from the neuroepithelium of the optic cup. They share similar functions as progenitors of the early retina, such as expression of Chx10 and Pax6 genes. It is not agreed upon whether epithelial cells of the ciliary body have stem cell properties. However, it has been found that these cells can be cultured and transplanted into retinas that are injured, in order to replace neurons that were previously lost. However, there is not much known about what factors regulate the proliferation of stem cells. Hence the authors were interested in finding the effects of GABA on proliferation of retinal cells. Their results showed that non-pigmented epithelial cells in chickens ‘express extrasynaptic-like GABAA receptors’ that have the ability to regulate cell proliferation. It has been found that inhibiting these ‘GABAA receptors’ also causes a decrease in proliferation of retinal progenitor cells and non-pigmented epithelial cells in 'the intact E8 retina’. <ref name="PMID22590629"/>

|
[[File:Gaba-effects-retina.JPG|thumbnail|250px|'''GABAA receptor mediated effects on retinal progenitor cell proliferation'''
]]
|}

-------------------

===The impact of visible light on the immature retina===

<pubmed>22405869</pubmed>

The authors mentioned in this article <ref name="PMID22405869"><pubmed>22405869</pubmed></ref> that they were interested in investigating the effect of light on postnatal eye development in mice, because mice are born with fused eyelids, which separate 12 days after birth. Before the eyelids separate, the retina develops in mice with very little radiation from light. It is believed that the darkness plays a role in the development of the retina in mice, which is why their eyelids are fused for 12 days after birth. Therefore the authors were interested to see what effect light would have on postnatal retinal development of mice, with special interest in retinal ganglion cells (RGC). In their experiment, they surgically opened the eyelids on the right eyes of some of the mice to expose them to visible light 12 hours per day, while they left some other mice in the dark after surgical separation of their eyelids. They also kept the left eyes of the mice naturally fused as controls in the experiment. Their results showed that early light exposure in mice causes a decrease in retinal ganglion cells because it affects cellular apoptosis in the retina. The authors also observed that early exposure to light in mice causes lumican mRna transcription to resume and to quickly increase. (Lumican normally stays silent in retina after birth).

---------

===MIP/Aquaporin 0 Represents a Direct Transcriptional Target of PITX3 in the Developing Lens===

<pubmed>21698120</pubmed>

{| width=800px
|-
|PITX3 plays a siginificant role in the development of lens in vertebrates. If there is a deficiency is PITX3, it causes a range of problems in humans such as microphthalmia, Peter’s anomaly, or isolated cataracts. Mutation of PITX3 also causes degeneration of the lens in zebrafish and mice. It is therefore important to understand what factors may affect the decrease in PITX3, as a normal level of PITX3 is needed to maintain normal eye development. The authors wanted to investigate specific genes which are affected by PITX3. Previous research has shown that MIP and Aquaporin causes defects in the lens in both mice and humans. MIP and Aquaporin are targeted by PITX3, so their imbalance is interrelated in the cause of defects in the lens. Therefore it has been previously proven that PITX3 is needed for normal development of the lens. However, there has not been much information previously known regarding the exact effect that PITX3 has, or the specific genes it targets. Since MIP and Aquaporin is common genes found in humans, mice and zebrafish, the authors <ref name="PMID21698120"><pubmed>21698120</pubmed></ref> chose to study these genes to understand the pathway that PITX3 takes and its exact involvement in the development of the lens. Their results proved that deficiency in MIP and Aquaporin indeed affects normal development of the lens, and it is indeed related to deficiency in PITX3. However, there is still more research needed to understand PITX3 and the genes it interacts with, and their effect in ocular development.

|
[[File:Mip1-expression-in-pitx3.jpg|thumbnail|250px|'''Analysis of mip1 expression in pitx3-mo and control embryos via in situ hybridization and RT-PCR''']]
|}

-----------

<pubmed>22496813</pubmed>

This research <ref name="PMID22496813"><pubmed>22496813</pubmed></ref> studied c-Jun N-terminal Kinase (JNK) activation in the retina of newborn rats

[[File:JNK1.png]]

<pubmed>20544023</pubmed>

<pubmed>20459797</pubmed>

[http://www.advancedcell.com/patients/clinical-trial-information/ Advanced Cell Technology]- A biotechnology company which is currently running two clinical trials that utilise human embryonic stem cell derived retinal pigmented epithelial cells. These trials are examining the possibility of using these cells to treat stargardt's macular dystrophy and dry age-related macular degeneration<ref><pubmed>22281388</pubmed></ref>.

----

===LRP5 is required for vascular development in deeper layers of the retina===

<pubmed>20652025</pubmed>

{| width=800px
|-
|
The lipoprotein receptor-related protein 5 (LRP5) has a significant function in the development of retinal vasculature.<ref name="PMID20652025"><pubmed>20652025</pubmed></ref> Research has shown that mutations of the LRP5 causes loss of function, due to incomplete development of retinal vessel network, in both humans and mice. The authors investigated how mutations occur in the LRP5, which leads to abnormal development of the retinal vasculature. They have studied retinal endothelial cells in mutant mice in their study. Their results showed that in retina with mutated LRP5, endothelial cells in the retinal vasculature primarily produced cell clusters in the inner-plexiform layer instead of migrating into deeper layers of the retina to form normal retinal vasculature. The authors also discovered that there was a decrease in Slc38a5, which is a “a Müller cell-specific glutamine transporter”, in mice with mutated LRP5. Their results lead the authors to conclude that normal LRP5 is very important in the development of normal retinal vasculature due to their role in causing migration of retinal endothelial cells in the deeper layers of the retina. LRP5 is also important for retinal interneurons and Müller cells to function correctly.

|
[[File:Retina-cell-clusters.JPG|350px|thumbnail|'''Endothelial cells form thick clusters in the LRP5 mutant retina''']]
|}

-----------------

==Useful Links==

{{External Links}}

[http://www.youtube.com/watch?v=Xme8PA6xv-M Visualisation of eye development in the embryo]

[http://www.embryo.chronolab.com/sense.htm Embryonic Development of the eye]

==Glossary==

'''Accommodation''' - changing the focal length of the lens in order to focus on an object.

'''Downstream genes''' - genes that are activated by other "upstream genes".

'''Ectoderm''' - outermost layer of germ cells in an early embryo.

'''Endoderm''' - innermost layer of germ cells in an early embryo.

'''Glial cells''' - non-neuronal cells that provide structure and protection to neurons as well as producing myelin.

'''Inductive signaling''' - a process whereby the secretion of factors from one cell or tissue triggers a response in another.

'''Lens vesicle''' - the cavity of invaginated ectoderm from the optic placode that will form the lens.

'''Macula''' - a highly pigmented, oval-shaped area located near the centre of the retina. Important for visual acuity.

'''Mesenchyme''' - undifferentiated, loose connective tissue.

'''Mesoderm''' - middle layer of germ cells in an early embryo.

'''Mesothelium''' - the epithelial layer of the mesoderm.

'''Myelinisation''' - development of a myelin sheath around a nerve fibre.

'''Neural crest''' - a portion of the ectoderm situated next to the neural tube.

'''Neural groove''' - a large invagination on the dorsal surface of the embryo which will close off and form the neural tube.

'''Neural tube''' - hollow structure that results from the folding of the neural plate and eventually forms the central nervous system.

'''Neuroblastic layer''' - a layer of immature cells that differentiate to form either glial cells or neurons. The retina has two of these (an inner and outer).

'''Neuroectoderm''' - portion of the ectoderm that develops to form the central and peripheral nervous systems.

'''Optic chiasm''' - the point at which the optic nerves meet and cross over.

'''Optic cup''' - the structure that is formed after the optic vesicle folds in upon itself. This will form the retina.

'''Optic globe''' - a term that refers to the optic cup, lens vesicle and surrounding mesenchyme collectively.

'''Optic placode''' - area of thickened ectoderm that gives rise to the lens of the eye.

'''Optic stalk''' - a long, narrow cavity that will produce the optic nerve.

'''Optic vesicle''' - a cavity that buds off from the neural tube and gives rise to the optic cup.

'''Upstream genes''' - genes that activate one or more other "downstream genes".

'''Vascularise''' - to invade with blood vessels.

==Image Gallery==
<gallery>
Image:Eye_diagram_bandw.jpg‎ | Basic structure of the human eye.
Image:Stage14 sem2b-limb.jpg | A Stage 14 embryo showing the location of an otic placode.
Image:Stage 13 image 060.jpg | A cross section showing the organisation of the developing brain, the optic vesicle and the lens (optic) placode.
Image:Formation of the optic vesicle 1.jpg | Early formation of the optic vesicle from the neural groove.
Image:Formation of the optic vesicle 2.jpg | The optic vesicle at a later stage, showing the optic stalk.
Image:Formation of the optic nerve and chiasm 1.jpg | A recognisable brain and eye structure in later development.
Image:Formation of the optic cup 1.jpg | Mechanism of optic cup formation.
Image:Formation of the optic cup 2.jpg | Layers of the optic cup in retina development.
Image:Formation of the retina 1.jpg | Cross-section of the primitive retina showing cell types and layers.
Image:Formation of the retina 2.jpg | Cross-section of a developed retina showing cell types and layers.
Image:Formation of the lens 1.jpg | The importance of the optic cup in lens differentiation.
Image:Formation of the lens 2.jpg | The lens placode separates from the ectoderm and migrates into the mesoderm forming the lens vesicle.
Image:Formation of the choroid and sclera 1.jpg | The choroid and sclera derives from mesenchyme surrounding the optic cup.
Image:Formation of the eyelid 1.jpg | Small grooves in the ectoderm of the head - the precursors to an eyelid.
Image:Formation of the eyelid 2.jpg | The eye at an advanced stage of embryonic development. Note however, that the eyelids remain fused until much later.

</gallery>

==References==
<references/>

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--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

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{{2012Projects}}

2012 Group Project 1

2012-10-02T13:17:31Z

Z3254758: /* Aqueous Chambers */

[[File:Eye_collage_2.jpg|right|830px]]

=Vision Development=

==Introduction==

Eyes are an important sensory organ shared across many different species and allow organisms to gather useful visual information from their environment. The visual system uses light from the environment and processes this information in the brain for visual perception. The visual system is complex, and is made up of various structures that work together to form vision. Each of the structures in the eye have specific tasks which contribute to the visual system. Knowledge of how the eye develops extends as far back as Aristotle more than 2000 years ago, and current knowledge shows that most of the crucial events of eye development occur in the embryological stage. The eye is an interesting model for studying the development of tissues in organisms, as it consists of cells from several parts of the embryo including the head ectoderm, neural ectoderm and mesoderm. From its many origins the cells come together and differentiate to produce the complex organ that is the eye. During this period there are many examples of inductive signaling, as the tissues coordinate their development throughout this elegant process.

The main anatomical structures of the eye are as follows:
{|
|
* Cornea

* Sclera

* Choroid

* Iris

* Ciliary body

* Lens

* Anterior chamber

* Posterior chamber

* Retina

* Optic nerve

|[[File:eye_diagram_bandw.jpg|right|250px|thumb|Basic structure of the human eye.]]
|}
[[File:Eyediagramcolour1.JPG|550px]]

==Research History==

=== '''Brief Timeline of Historical Developments on the Eye and its Embryology''' ===

{| width=800px
|-bgcolor="CEDFF2"
| width=100px|'''Time'''
| width=700px|'''Discovery'''

|-bgcolor="F5FAFF"
| '''Ancient Egyptians'''
| First to document cataracts. It is described as being 'the white disease of the eye' or 'darkening of the pupil.' <ref>Edwards, D.D. (1996). Ophthalmology before Hippocrates. In the History of Ophthalmology, ed. D.M. Albert and D.D. Edwards. Cambridge, Mass.: Blackwell Science.</ref> The Egyptians had some knowledge of the eye, however it is not known how much of the anatomy of the eye was known in their era.

|-bgcolor="CEDFF2"
| '''535 BC'''

|
Ancient Greek philosopher Alcmaeon conducted dissection of humans for the first time in recorded history. This included dissection of the eye. However, not much is known about which anatomical features he discovered. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17.">Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17.</ref>

|-bgcolor="F5FAFF"
| '''384- 322 BC'''

| [[File:Aristotle-eye.jpg|200px|thumbnail|The eye according to Aristotle.<ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "> Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau </ref> Note the lens is missing, and there are three vessels drawn that was believed to transport fluid to and from the eye.<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
]]
Aristotle performed dissections of animal embryos.<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

When Aristotle described the embryo of a ten day old chicken, he wrote "The eyes about this time, if taken out, are larger than beans and black; if their skin is removed the fluid inside is white and cold, shining brightly in the light, but nothing solid." <ref name="Magnus, H. (1998). Ophthalmology of the ancients. In J. Hirschberg (Ed.), The History of Ophthalmology: The monographs, Vol. 4, Part 1 (F.C. Blodi, Trans.) Bonn: Wayenborgh.">Magnus, H. (1998). Ophthalmology of the ancients. In J. Hirschberg (Ed.), The History of Ophthalmology: The monographs, Vol. 4, Part 1 (F.C. Blodi, Trans.) Bonn: Wayenborgh.</ref>

Aristotle believed that the eyes started forming during early embryogenesis, however, he also believed that the eyes are the last organs to form completely, and he incorrectly thought that the eyes shrink in later embryonic development. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press.">Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press.</ref> .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"

| '''340 BC'''

| Lens is thought to have been discovered by Hippocrates, due to his descriptions of the contents of the internal eye There has been studies in chick development later on by followers of Hippocrates. They claimed that eyes were visible in early embryogenesis. .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
|-bgcolor="F5FAFF"
|'''25 BC - 50 AD'''

| [[File:Celsus-eye.jpg|150px|thumb|The eye according to Celsus. <ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "/>
Note the lens is placed in the centre of the eye, in the vitreous.<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> ]]

Aulus Cornelius Celsus wrote a Roman medical text called 'De Medicina' in which he wrote that the lens was the part of the eye from which vision originated. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.">Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.</ref> Celsus also incorrectly drew the lens in the center of the globe in his diagram of the eye. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

|-bgcolor="CEDFF2"
| '''23-79 AD '''
|
Pliny the Elder said that the eye is the last of the organs to develop in the womb <ref name="Magnus, H. (1998). Ophthalmology of the ancients. In J. Hirschberg (Ed.), The History of Ophthalmology: The monographs, Vol. 4, Part 1 (F.C. Blodi, Trans.) Bonn: Wayenborgh."/>
|-bgcolor="F5FAFF"
| '''98-117 AD'''

| [[File:Rufus-eye.jpg|150px|thumb|The eye according to Rufus of Ephesus. <ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "/>
Note the lens is placed in the correct position, behind the iris of the eye <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> ]]

Rufus of Ephesus identified the lens as being located in the anterior part of the eye, close to the pupil. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

His diagram illustrates that he knew the correct position of the lens as being directly behind the iris, in the anterior part of the eye, and not in the centre as was previously depicted by others before him.

|-bgcolor="CEDFF2"
| '''130-200 AD'''

| [[File:Galen-eye1.jpg|150px|thumb|The eye according to Galen. <ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "/> ]]

Claudius Galen practised medicine in Rome. He wrote:

"1. Within the eye the principal orgran of sensation is the crystalline lens.

2. The sensation potential comes from the brain and is conducted via the optic nerves.

3. All other parts of the eyeball are supporting structures." <ref> Hirschberge, J. (1982). Antiquity, Vol. X in the History of Ophthalmology (F.C. Blodi, Trans.) Bonn: Wayenborgh. pp. 280 </ref>

Galen thought that the lens was produced from the vitreous. He also believed that the retina’s function was to give nourishment to the lens and vitreous, and to carry visual information to the brain from the lens. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

|-bgcolor="F5FAFF"

| '''1514-1564'''

| Andreas Vesalius published his anatomy book "De Humani Corporis Fabrica in 1543. He had the misconception that the lens was located in the centre of the eyeball. .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> He also wrote that the lens functioned "like a convex lens made of glass" <ref name="Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.">Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.</ref> pp. 48
|-bgcolor="CEDFF2"
| '''1535-1606'''

| Georg Bartisch correctly drew a diagram of the lens placed behind the iris in his book 'Ophthalmodouleia: das ist Augendienst'. <ref name="Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>
|-bgcolor="F5FAFF"

| '''1537-1619'''

| Fallopio Hieronymus Fabricius ab Aquapendente studied anatomy and embryology. He studied chicken embryos, and thought that chalazae (which comes from egg white) gives rise to the eyes. He also drew the lens directly behind the iris in a diagram in is book 'Tractatus de Oculo Visuque Organo. <ref name="Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

|-bgcolor="CEDFF2"
| '''1583'''

| Felix Platter published his book 'De corporis Humani Structura et Usu, after he performed dissections of human bodies. He believed that the retina is the primary visual organ in the eye. .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="F5FAFF"
| '''1619'''
| Scheiner is given credit to be the first person to correctly draw the diagram of the anatomy of the eye. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
|-bgcolor="CEDFF2"
| '''1672'''
| Marcello Malpighi described the embryonic development of the chicken. He drew many detailed diagrams of the chick eye. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1665'''
| Nicolaus Steno identified the choroid fissure in his study of a developing embryo of a chicken. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="CEDFF2"
| '''1754'''

| Albrecht von Haller studied the embryology of the eye. With help from his student Johann Gottfried Zinn, he contributed to the understanding of the development of the ciliary body, ciliary zonule, and their relationship with the lens and vitreous. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1817'''

| Christian Pander discovered the three embryonic germ layers, which he wrote about in his book. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/> Pander was the first to think of 'the optic vesicles as lateral evaginations' of the 'prosencephalon'; however, he was incorrect about the details regarding how 'the eye develops from these evaginations'. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="CEDFF2"
| '''1828-1837'''

| Karl Ernst von Baer studied embryology. He discovered that the optic vesicles were 'outgrowths of the embryonic forebrain' <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> which he believed was caused by pressure from fluids in the central nervous system. Von Baer also believed that the optic vesicle opens to form the pupil, and that fluid in the optic vesicle coagulates to form the vitreous body and lens. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1830'''

| Emil Huschke discovered that the lens forms from the invagination of the surface ectoderm. He concluded that the lens hence does not form ‘from the fluid of the optic vesicle’ <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> as previously thought.
|-bgcolor="CEDFF2"
| '''1832'''

| Emil Huschke wrote in his manuscript ‘Ueber die erste Entwinkenlung des Auges und die damit zusammenhängende Cyklopie’ that the lens capsule forms from the outer surface ectoderm, which detaches and moves back inward, which is later enclosed again by several membranes, such as by the cornea. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

Huschke also described how the optic cup and choroid fissure forms. He discovered that the optic vesicles are produced from the two-layered optic cup. However, he incorrectly described the destiny of the ‘individual optic cup layers’. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

|-bgcolor="F5FAFF"
| '''1838'''
| Matthias Jakob Schleiden and Theodor Schwann formulated the ‘cell theory’: “All living things are formed from cells, the cell is the smallest unit of life, and cells arise from pre-existing cells.” <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
|-bgcolor="CEDFF2"
| '''1839'''

| Theodor Schwann contributed a better understanding of the development of the lens through studying the foetus of a pig, which he wrote about in his book ‘Mikroskopische Untersuchungen Über Die Uebereinstimmung in Der Struktur Und Dem Wachsthum Der Thiere Und Pflanzen’. He wrote that the lens is made of ‘concentric layers’ of fibres which proceeds from an anterior to posterior direction. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1842'''
| Robert Remak gave the current names to the three embryonic germ layers: ectoderm, mesoderm and endoderm. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"
| '''1843'''
| Wilhelm Werneck published his book ‘Beiträge zur Gewebelehre des Kristallkörpers’. He wrote that the contents inside of the lens is not made of fluids, as was previously believed. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/> Werneck also discovered that the fibers of the lens continues to grow from the outside to the centre during embryogenesis. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

|-bgcolor="F5FAFF"
| '''1855'''

| Robert Remak wrote his book ‘Untersuchungen über die Entwickelung der Wirbelthiere’. He wrote about what he discovered in his studies of the development of the eye in the embryos of chickens, frogs, and rabbits. He wrote very descriptively about the embryology of lens formation, amongst other topics. He discovered that the ectoderm gives rise to the lens placode. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

|-bgcolor="CEDFF2"
| '''1858'''
| Henry Gray published his book 'Anatomy, Descriptive and Surgical'. He had also previously studied the embryonic development of the optic nerve and retina of chickens.
|-bgcolor="F5FAFF"
| '''1877'''
| Paul Leonhard Kessler wrote about the embryonic development of the lens in mice in his book ‘Zur Entwickelung des Auges der Wirbelthiere. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"
| '''1891'''
| Vincenzo Colucci studied newts and discovered their ability to regenerate the lens.<ref> Tsonis, P. A. (2001). Regeneration of the Vertebrate Lens and Other Eye Structures. eLS. (Online Publication). DOI: 10.1038/npg.els.0001102 </ref>
|-bgcolor="F5FAFF"
| '''1892'''
| Dr. Oscar Hertwig published his book ‘Text-Book of the Embryology of Man and Mammals. <ref> Hertwig, O. Text-book of the embryology of man and mammals. S. Sonnenschein 1901. (Translated from the 3d German ed. by Edward L. Mark.) </ref> It contains a very detailed description of the development of the eye, according to the findings at that time. [http://embryology.med.unsw.edu.au/embryology/index.php?title=Book_-_Text-Book_of_the_Embryology_of_Man_and_Mammals_16-2#The_Development_of_the_Eye]
|-bgcolor="CEDFF2"
| '''1895'''
| Gustav Wolff also independently studied newts and discovered their ability to regenerate the lens. .<ref> Tsonis, P. A. (2001). Regeneration of the Vertebrate Lens and Other Eye Structures. eLS. (Online Publication). DOI: 10.1038/npg.els.0001102 </ref>

|-bgcolor="F5FAFF"

| '''1900'''
| Carl Rabl published his book ‘Uber den Bau und die Entwicklung der Linse’. He wrote about the development of the lens in mammals, fish, birds, reptiles, and amphibians. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"
| '''1901'''
| Hans Spemann published his findings from his experimental studies about the formation of the lens in the frog. He found that the optic cup needed to be in contact with the ectoderm for normal development of the eye. <ref> Spemann, H. (1901). Über Correlationen in der Entwicklung des Auges. Verhand. Anat. Ges. 15: 61-79. </ref> <ref> Saha, M. (1991). Spemann seen through a lens. In Gilbert, S. F. (ed.). A Conceptual History of Modern Embryology. Plenum Press, NY. pp. 91-108.</ref>
|-bgcolor="F5FAFF"
| '''1906'''
| Brown ‘s book “The Embryology Anatomy and Histology of the Eye” was published. It contained detailed descriptions of the embryonic development of the eye according to the knowledge current at that time, mainly based on observations from embryos of rabbits and chickens. <ref> Brown, E.J. (1906). The Embryology Anatomy and Histology of the Eye. Chicago: Hazlitt & Walker. 1906 </ref>

|-bgcolor="CEDFF2"
| '''1907'''

| John Clement Heisler published his book ‘A Text-book of embryology’. It contains a chapter detailing the embryonic development of the eye, according to the knowledge current at that time. The book’s copyright has expired, so it can be viewed free online: [http://archive.org/details/atextbookembryo01heisgoog]

Julius Kollman also published his book 'Atlas of the Development of Man'. It contained very detailed description and illustrations showing the embryonic development of the human according to the knowledge current at that time. His illustrations were reused by many others after his time and built upon for further refined understanding of the embryology of the human.

Here are examples of Julius Kollman's excellent illustrations showing eye development in various stages:

'''Formation of Primary Optic Vesicle:'''
<gallery>
File:Kollmann691.jpg|The blue part at the bottom is the endoderm. The pink middle layer is the mesoderm. The top yellow layer is the ectoderm. The fold labelled as 'augenfeld' is the place where the optic vesicle will form.
File:Kollmann692.jpg|The eye area (augenfeld) is a bowl shaped bulge still located on the side walls.
File:Kollmann693.jpg| The neural tube is shown after removal of all of the ectoderm and ventral organs, such as heart, gut tube, etc. The primary optic vesicle forms a slightly flattened hollow protrusion on the forebrain.
File:Kollmann694.jpg|The lateral surface of the primary optic vesicle is slightly depressed, showing the first sign of the emergence of the secondary optic vesicle
</gallery>

'''Development of Lens:'''

<gallery>
File:Kollmann695.jpg|The bulging lateral wall of the primary optic vesicle is covered by a fairly well demarcated lens plate, a direct continuation of the ectoderm. Between the optic vesicle and the lens pit are some flattened spindle-shaped cells. In the adjoining mesoderm are cross-sections of capillaries.
File:Kollmann697.jpg|The lens still hangs together with the ectoderm. The primary eye vesicle is indented with respect to the lens. Between the lens and the lateral plate of the optic vesicle is a narrow space, which allows area to further develop later.
File:Kollmann698.jpg|4th Week of development. The internal organisation shows the secondary optic vesicle. A: The rear wall of lens is noticeable and is enveloped by mesoderm. B: The edges of the lens pit is already grown and the lens vesicles are formed, which is still related to the remaining ectoderm.
File:Kollmann699.jpg|The lens has now cut off from the ectoderm, but is still very superficial. Between it and the lateral lamina of the optic cup, there is a considerable space. The eye stalk has become longer and is enclosed together with the optic cup and lens of the mesoderm. The cornea, sclera and choroid make gradual development.
</gallery>

|-bgcolor="F5FAFF"

| '''1921'''
| Bailey and Miller published their textbook “Text-Book of Embryology “. <ref> Bailey, F.R. and Miller, A.M. (1921). Text-Book of Embryology. New York: William Wood and Co. (Note- This book is only at an early edited stage)</ref> It contains detailed description of the development of the embryonic eye according to the knowledge current at that time. [http://embryology.med.unsw.edu.au/embryology/index.php?title=Book_-_Text-Book_of_Embryology_18]

|-bgcolor="CEDFF2"
| '''1925'''

| Mann published his research article, in which he gives a detailed account of the development of the human iris. He divided the development of the iris into four stages: weeks 4-7 (before the ectodermal iris forms or before the anterior chamber forms); weeks 7-11 (anterior chamber appears, and mesodermal iris forms); weeks 11-12 (ectodermal iris forms); 3-8 months (muscles of the pupil forms from ectodermal iris, and the central portion of the mesodermal iris atrophies to make the pupil clear). <ref name="PMID18168466"><pubmed>18168466</pubmed></ref>
O Leser also published an article detailing the development of extraocular muscles in mammals he studied. <ref name="PMID18168498"><pubmed>18168498</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1939'''
| Holtfreter <ref> Holtfreter, J. (1939). Gewebeaffinitat, ein Mittel der embryonalen
Formbildung. Arch. Exp. Zellforsch. 23, 169-209. </ref> studied amphibians and observed that that the development of the eye stops at the ‘optic vesicle stage’ if there is no contact ‘with the epidermis and neural crest driven mesenchyme’. <ref name=”PMID11023863”><pubmed>11023863</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1955'''
| Barber published his book ‘Embryology of the human eye’. <ref> Barber AN: Embryology of the human eye. St. Louis. CV Mosby 1955</ref> In contains detailed descriptions of the embryological development of the human eye according to the knowledge current at that time. It contains many photographs of the eye at different stages of development.

|-bgcolor="F5FAFF"
| '''1957'''
| Coulombre studied a chicken embryo to find the role of intraocular pressure in the development of the chick’s eye, especially in regards to its control of the size of the eye structures. <ref name="PMID13469954"><pubmed>13469954</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1958'''
| Coulombre studied the development of the cornea and how it develops its transparency. <ref name="PMID13563560"><pubmed>13563560</pubmed></ref> He also studied the development of corneal curvature. <ref name="PMID 13519969"><pubmed> 13519969</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1962'''
| Coulombre studied the development of the conjunctival papillae and scleral ossicles. <ref name="PMID 14023393"><pubmed> 14023393</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1963'''
| Coulombre studied the development of lens fibers and their orientation. <ref name="PMID14077035"><pubmed>14077035</pubmed></ref> He also studied the development of pigmented epithelium. <ref name="PMID14023394"><pubmed>14023394</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1964'''

| Coulombre further studied the development of the lens to determine the role of the lens in eye growth. <ref name="PMID14189921"><pubmed>14189921</pubmed></ref> He also studied the role of thyroid in the development of the cornea and the development of corneal transparency. <ref name="PMID14211912"><pubmed>14211912</pubmed></ref> Mann also published his work called ‘The development of the human eye’, which contains detailed description of the embryonic development of the eye according to current knowledge at that time. <ref> Mann I. The development of the human eye. New York: Grune and Stratton 1964</ref>

|-bgcolor="CEDFF2"
| '''1965'''
| Coulombre published his findings regarding the regeneration of the neural retina from pigmented epithelium in the embryo of chickens. <ref name="PMID5833111"><pubmed>5833111</pubmed></ref> Smelser also published his findings on the embryological development and morphology of the lens. <ref name="PMID14340157"><pubmed>14340157</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1966'''

| Formation of the face and orbit occurs from the differentiation of neural crest cells. <ref name="PMID5969670"><pubmed>5969670</pubmed></ref> O’Rahilly also published findings of the development of the eye in the early stages of human embryos. <ref> O'Rahilly, R. 1966 The early development of the eye in staged human embryos. Contr. Embry. Carnegie Inst., Wash., 38: 1–42</ref>

|-bgcolor="CEDFF2"
| '''1968'''
| Findings of the postnatal development of the retina of rats was published. <ref name="PMID5640327"><pubmed>5640327</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1969'''

| Mann again published his work called ‘The development of the human eye’. He stated that that the lens in humans forms completely from the ectoderm. <ref name=”Mann I. The Development of the Human Eye. New York, USA: Grune & Stratton, Inc; 1969”> Mann I. The Development of the Human Eye. New York, USA: Grune & Stratton, Inc; 1969</ref> Coulombre also studied the development of the lens, and took note of its size, shape and orientation throughout its developmental stages. <ref name="PMID 5772716"><pubmed> 5772716</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1970'''
| Coulombre again further studied the regeneration of the neural retina from pigmented epithelium of embryos of chickens. <ref name="PMID 5472476"><pubmed> 5472476</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1971'''

| Coulombre further studied the development of the lens. This time he focused on analysing the histological mechanisms in the reconstitution of the lens from implanted lens epithelium. <ref name="PMID 4925671"><pubmed> 4925671</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1973'''
| A research article was published, detailing the embryonic development of the retina of humans. <ref name="PMID 6650859"><pubmed> 6650859</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1976'''

| Geeraets published his observations of the closure of the embryonic optic fissure in golden hamsters, using the electron microscope. <ref name="PMID 1266776"><pubmed> 1266776</pubmed></ref> Kornneef also published an article based on his studies of the development of connective tissue in the human orbit. <ref name="PMID 1020699"><pubmed> 1020699</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1981'''
| A research article was published detailing how myelin forms in the optic nerve of humans. <ref name="PMID 7224936"><pubmed> 7224936</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1983'''
| O’Rahilly’s further research developments was published, reporting the timing and sequence of events in the development of the embryonic human eye. <ref name="PMID 6650859"><pubmed> 6650859</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1990'''

| Van Driell et al. <ref>Driell, D. Van; Provis, J.M.; Billson, F.A.: Early differentiation of ganglion, amacrine, bipolar and Muller cells in the developing fovea of the human retina. J. Comp. Neurol. 291: 203-219.</ref> studied the manner in which amacrine, bipolar, retinal ganglion cells, and Muller cells differentiate in the developing fovea of the retina of a 15-week old human foetus. <ref name="PMID1628748"><pubmed>1628748</pubmed></ref> Tripathy also published an article providing evidence that the lacrimal glands in humans originates from the neuroectoderm. <ref name="PMID2406219"><pubmed>2406219</pubmed></ref>

|}

==Development, Structure and Function of Ocular Components==

The eye itself is formed from several components; notably the optic placode of the head ectoderm, the optic vesicle from the neural tube, and mesenchyme from the mesoderm and neural crest cells. The optic placode contributes the lens to the eye, the optic vesicle gives rise to layers of the retina, while the mesenchyme will produce the ciliary body, iris, choroid and sclera.<ref>http://www.vetmed.vt.edu/education/curriculum/vm8054/eye/EMBYEYE.HTM</ref> Cells from the neural tube will also produce the optic nerve, which receives nerve impulses from the retina of the eye. Eyes initially form as laterally paired structures and migrate medially in the human embryo. In other animals such as birds and lizards, the eyes do not migrate and develop laterally on the head. The optic placodes become prominent on the surface of the embryo at approximately Stage 14 of development.

[[File:Stage14 sem2b-limb.jpg|200px|thumb|left|A Stage 14 embryo showing the location of an otic placode.<ref name="http://embryology.med.unsw.edu.au/embryology/index.php?title=ANAT2341_Lab_6_-_Early_Embryo">http://embryology.med.unsw.edu.au/embryology/index.php?title=ANAT2341_Lab_6_-_Early_Embryo</ref>]] [[File:Stage 13 image 060.jpg|400px|thumb|center|A cross section showing the organisation of the developing brain, the optic vesicle and the lens (optic) placode.<ref name="http://embryology.med.unsw.edu.au/embryology/index.php?title=ANAT2341_Lab_6_-_Early_Embryo"/>]]

===Optic Nerve===

The optic nerve consists of nerve fibres that transmit information from the retinal photoreceptor cells to the brain. The optic nerve is formed from the optic stalk, which develops as the optic vesicle migrates from its origin in the neural tube to its destination - the surface ectoderm - where it will fuse with the optic placode (also known as the lens placode, which will contribute the lens to the eye).<ref name="PMID11687490"><pubmed>11687490</pubmed></ref>

[[File:Formation of the optic vesicle 1.jpg|400px|thumb|left|Fig. 1: Early formation of the optic vesicle from the neural groove.]] [[File:Formation of the optic vesicle 2.jpg|400px|thumb|center|Fig. 2: The optic vesicle at a later stage, showing the optic stalk.]]

As can be seen in Figure 1 above, the optic vesicle forms from the neural tube. However, note that the neural tube has not yet closed, and is still the neural groove at this point. Figure 2 then shows the optic vesicle at slightly later stage in the same simplified cross-section of the embryo, as it migrates from the neural tube to the surface ectoderm. Note the presence of the optic stalk which links the optic vesicle to the neural tube. Later in development, this primitive structure will become the optic nerve, which will link the eye to the brain.

The nerve fibres themselves will initially originate from the retinal ganglion cells in the eye during week 6.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008">Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008</ref> After two weeks, these fibers will have grown along the inner wall of the optic stalk and have reached the brain. They grow both in length and width, with the nerve fibres filling the hollow optic stalk to form the solid optic nerve. More than one million nerve fibers will eventually make up the optic nerve, along with glial cells which arise from the inner wall of the optic stalk itself.<ref><pubmed>1451666</pubmed></ref> Myelinisation of the optic nerve begins much later in development at around 7 months, beginning at the optic chiasm and moving towards the eye.<ref><pubmed>7224936</pubmed></ref> The optic chiasm forms just before the nerves reach the brain, and is where half the nerve fibres from each eye will cross over to the opposite side of the brain. This is demonstrated in Figure 3. Note the crossing over of the optic nerves just before they enter the brain, at the optic chiasm. This organisation is now much more familiar, with the eyes near the ectoderm and the optic nerve leading through the mesoderm to the brain buried deep in the embryo.

[[File:Formation of the optic nerve and chiasm 1.jpg|400px|thumb|center|Fig. 3: A recognisable brain and eye structure in later development.]]

===Retina===

The retinal component of the eye is formed when the optic vesicle folds in upon itself, forming the optic cup (see Figure 4). In doing so it creates two layers - an inner wall and an outer wall of the optic cup (Figure 5). These two layers of the optic cup will give rise to the two layers of the retina - the inner neural retina, and the outer pigmented epithelium.<ref name="PMID11687490"/> Note the existence of the space between the two layers of the retina. This is known as the intraretinal space and disappears by the 7th week of development, however the two layers never completely fuse and can become separated as a result of physical trauma to the head - leading to a detached retina and loss of vision.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/>

The inner wall of the optic cup, which will give rise to the neural retina, consists of a layer of pseudostratified cells (see Figure 6) that later differentiate into rod, cone, bipolar, ganglion, horizontal, amacrine and glial cells of the retina (Figure 7).<ref name="PMID18168748"><pubmed>18168748</pubmed></ref> The outer wall of the optic cup consists of a layer of cuboidal cells that contain melanin - the light absorbing pigment. The function of this layer is to absorb light and prevent internal reflection of light within the eye, which would impair our ability to form distinct images. Interestingly, in some animals such as cats, this layer actually reflects light intentionally to increase the amount of light available to the eye in low-light conditions. This is why cats seem to have eyes that glow in the dark.<ref>http://dialspace.dial.pipex.com/agarman/bco/fact4.htm</ref>

[[File:Formation of the optic cup 1.jpg|400px|thumb|left|Fig. 4: Mechanism of optic cup formation.]] [[File:Formation of the optic cup 2.jpg|400px|thumb|center|Fig. 5: Layers of the optic cup in retina development.]]

The inner wall itself is divided into two components - the inner neuroblastic layer and the outer neuroblastic layer (see Figure 6). The outer neuroblastic layer forms the rod and cone cells while the inner neuroblastic layer forms the remaining cell types found in the retina - the bipolar, ganglion, horizontal, amacrine and glial cells (Figure 7).<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/> The organisation of the retina is interesting in that incoming light passes through several layers of these neural retina cells before it is detected by rod and cone cells at the back of the retina, and then nerve signals are passed back through the layers of neural retina cells that the light just passed through moments before - a seemingly strange design that the eye does not share with man-made light-capturing devices such as a camera (imagine putting the wires in front of the image sensor!).

Differentiation of the neuroblastic layers into neural retina cells occurs in a pattern both within the layers and across the retina. Cells differentiate from the inner neuroblastic layer to the outer neuroblastic layer, and differentiate from the central retina to the peripheral retina.<ref name="PMID18168748"/> The macula is first identifiable in week 22 when ganglion cells start to form multiple rows, and the primitive fovea begins to form at approximately the same time as a depression in the macula.<ref><pubmed>6462623</pubmed></ref> It is not until 15-45 months after birth that this area becomes exclusively populated by cone cells and becomes the fovea centralis - the area of the retina with the highest visual acuity.

[[File:Formation of the retina 1.jpg|400px|thumb|left|Fig. 6: Cross-section of the primitive retina showing cell types and layers.]] [[File:Formation of the retina 2.jpg|400px|thumb|center|Fig. 7:Cross-section of a developed retina showing cell types and layers.]]

===Ciliary Body===

The ciliary body consists of ciliary processes and three portions of fibres that constitute the ciliary muscles. It functions to maintain normal eye physiology as well as playing a direct role in accommodation.

During development, the ciliary processes form slightly posterior to the iris, developing from part of the anterior rim of the optic cup. It is thought that the folded structure of the ciliary processes is brought about by intraocular pressure and specific signalling pathways.<ref name="PMID16959249"><pubmed>16959249</pubmed></ref> While the ciliary muscles and the endothelial cells of the ciliary blood vessels are chiefly formed by mesenchymal cells<ref><pubmed>16249499</pubmed></ref>, the neural crest and neuroectoderm also contribute to their development.<ref><pubmed>12127103</pubmed></ref> The normal development of the ciliary body is dependent on the correct expression of bone morphogenetic protein (BMP)-4, which is a member of the transforming growth factor-β superfamily.<ref><pubmed>1222340</pubmed></ref> Napier and Kidson (2007) summarised numerous genes that have been associated with ciliary body development, however their direct roles have not been well documented.<ref name="PMID16959249"/>

===Iris===

The iris is a thin layer that develops at the end of the third month of development and is derived from the anterior rim of the optic cup. The stroma of the iris develops from cells of neural crest cell origin.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/> The muscles that are responsible for the dilation and constriction of the pupil (dilator pupillae and sphincter pupillae muscles) form from the neuroectoderm of the optic cup. These cells are initially epithelial cells that then transform into smooth muscle cells. <ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"></ref>. The invagination of the optic vesicle which creates the optic cup, also causes the formation of the optic cup lip. This is the region of the where the epithelium doubles back, separating the outer pigmented layer and the inner nonpigmented layer. This is the edge of the iris that borders on the pupil<ref><pubmed> Retinal and anterior eye compartments derive from a common progenitor pool in the avian optic cup</pubmed></ref>.

The final colour of the iris is not evident until the postnatal period. It is determined by a number of genes including IRF4, SLC24A4 and MATP<ref><pubmed>19710684</pubmed></ref>. Other features such as crypt frequency, furrow contractions, presence of peripupillary pigmented ring, and number of nevi also become evident during development<ref><pubmed>21835309</pubmed></ref>.

Mutations in Pax6 have been shown to cause partial or complete loss of the iris <ref><pubmed>12386935</pubmed></ref>.

===Lens===

The lens has its origin from the optic placode, which develops on the ectodermic surface of the embryo and migrates both medially and inwards into the embryo. The lens allows accommodation of the eye, and adjusts its thickness in order to focus on near or far objects. The study of lens development was one of the first to highlight the importance of inductive signaling in development, with Spemann's pioneering work at the start of the 20th century, finding that the absence of retinal development resulted in the absence of lens formation.<ref name="PMID11687490"/> Indeed, it has been consistently shown that the interaction of the migrating optic vesicle with the surface ectoderm of the head is vital in producing differentiation of the lens.<ref name="PMID15558475"><pubmed>15558475</pubmed></ref> The mechanism of interaction is complex but basically involves upstream genes switching on downstream genes, with the genes eventually producing specialised proteins which constitute the lens. The whole process starts with the signaling molecules from the optic cup initiating a thickening of the surface ectoderm of the head (Figure 8). It is thought that this region of specific ectoderm is responsive to the signaling molecules, as lens formation is incomplete or absent when ectoderm from the lateral portion of the embryo (i.e. non-head ectoderm) is exposed to the same inductive signaling processes.<ref name="PMID9216064"><pubmed>9216064</pubmed></ref> Pax6 has been shown to be one of the major genes required for differentiation of the lens, which in turn switches on transcriptional genes such as Sox 1, 2 and 3 among others - producing water-soluble proteins called crystallins - responsible for giving the lens its transparency and refractive properties.<ref name="PMID9609835"><pubmed>9609835</pubmed></ref>

[[File:Formation of the lens 1.jpg|400px|thumb|left|Fig. 8: The importance of the optic cup in lens differentiation.]] [[File:Formation of the lens 2.jpg|400px|thumb|center|Fig. 9: The lens placode separates from the ectoderm and migrates into the mesoderm forming the lens vesicle.]]

The lens placode invaginates from the head ectoderm and migrates into the mesoderm (Figure 9). Once this structure (now known as the lens vesicle) is in place opposite the optic cup, the combined structure is referred to as the optic globe and resembles a recognisable eye structure. The lens continues to differentiate further, as mentioned above, through the formation of crystallin proteins, which give the lens its unique properties and allows for the fine control over the degree of refraction that takes place.

===Aqueous Chambers===

There are both anterior and posterior aqueous chambers of the eye which contain aqueous humour. A space develops in the mesenchyme situated between the lens and cornea to form the anterior aqueous chamber. The mesenchyme located superficially to this chamber forms the mesothelium as well as the transparent portion of the cornea.

The posterior chamber develops from a similar space in the mesenchyme, however it is located between the iris and the lens. The anterior and posterior chambers are able to communicate with one another once the papillary membrane vanishes and the pupil is formed. This channel is known as the scleral venous sinus.<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011">Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011</ref>

Contained within the aqueous chambers is aqueous humor. The production of aqueous humor is dependant on the development of the ciliary body. It is produced in the ciliary processes and it’s production is a metabolic process driven by the delivery of oxygen and the removal of wastes via the ciliary circulation<ref><pubmed>20801226</pubmed><ref>.

===Cornea===

The cornea is the transparent, avascular, most anterior portion of the eye. It is responsible for conducting light into the eye and focusing it on to the retina, as well as maintaining the rigidity of the eyeball. It consists of 5 layers- the epithelium, Bowman’s layer, stroma, Descemet’s membrane and the endothelium.

The epithelium and endothelium of the cornea first appear during the 5th week of gestation. The epithelium of the external surface of the cornea is derived from surface ectoderm, while the mesenchyme is derived from the mesoderm<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"/>. The endothelium is a two-cell cuboidal layer which is made up of differentiated neural crest cells that were initially from the optic cup. By week 8 the endothelial cells begin to secrete a basement membrance which later forms Descemet’s membrane<ref><pubmed>6511224</pubmed></ref>. At approximately 16 weeks gestation the Bowman’s membrane begins to form from the thickening of the stroma that is located under the corneal epithelium<ref>Riordan-Eva P, Whitcher JP. Vaughn and Asbury's General Ophthalmology, Lange Medical Books/McGraw Hill. 2004:25–27</ref>. During the third month glycosaminoglycans secreted by fibroblasts form the ground substance of the cornea, with collagen fibrils and keratan sulphate also appearing around this time. Shortly after this tight junctions form between the endothelial cells<ref><pubmed>19481138</pubmed></ref>. Towards the end of the gestational period the cornea becomes larger due to the production of aqueous humor<ref>Yanoff M, Duker JS. Ophthalmology. Mosby; St. Louis, MO: 2004</ref>. The final transparent structure develops because hyaluronidase removes hyaluronic acid, thyroxine causes dehydration of the stroma, and the entire structure becomes avascular<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/>. Numerous genes have been implicated in the development of the cornea, these include, but are not limited to, PAX6, PITX2, FOXC1, MAF, TMEM114, SOX2, OTX2 and BMP4<ref><pubmed>18637741</pubmed></ref>.

===Choroid and Sclera===

The choroid and sclera are adjacent layers that surround the eye and act to vascularise and protect the eye respectively. They are formed from neural crest and mesoderm-derived mesenchyme which condenses around the optic cup and lens vesicle between weeks 5 and 7 of development to form a primitive eyeball structure known as the optic globe.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/> Blood vessels first start to appear in the choroid layer at approximately week 15, and arteries and veins can be distinguished by week 23.<ref>Development of the Choroid and Related Structures, K. Sellheyer, Eye (1990) 4, 255-261</ref> Inductive processes are thought to play a vital role during formation of the choroid and sclera; with the retinal pigmented epithelium inducing differentiation of the surrounding mesenchyme while at the same time the neural crest-derived mesenchyme contributing components to the retinal pigmented epithelium such as melanocytes.<ref name="PMID1628748"/> In addition to having functional roles themselves, the primitive choroid and sclera also contribute components to the developing ciliary body and cornea (Figure 10). In the adult eye, the choroid is continuous with the ciliary body and the sclera with the cornea.

[[File:Formation of the choroid and sclera 1.jpg|400px|thumb|center|Fig. 10: The choroid and sclera derives from mesenchyme surrounding the optic cup.]]

===Eyelids===

The eyelids are ectodermal and mesodermal in origin and are an extension of the skin which covers and protects the eye. Eyelid formation can be first noted during week 5 when small grooves develop in the surface ectoderm (Figure 11).<ref><pubmed>7364662</pubmed></ref> These small grooves deepen and extend into the mesoderm and the primitive eyelid structures grow towards one another, eventually fusing together during week 8.<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"/> It is not until week 26-28 that the eyelids will separate again. The ectoderm reflects over the developing cornea to form the conjunctival sac, a space that is filled by secretions from the lacrimal gland in order to allow smooth motions of the eyelid over the eye and also to clean the cornea and prevent accumulation of particles on the eye that may disrupt vision. By the time the eyelids separate, the eye has all its major components present (Figure 12), and further development consists mainly of growth and vascularisation.

[[File:Formation of the eyelid 1.jpg|400px|thumb|left|Fig.11: Small grooves in the ectoderm of the head - the precursors to an eyelid.]] [[File:Formation of the eyelid 2.jpg|400px|thumb|center|Fig. 12: The eye at an advanced stage of embryonic development. Note however, that the eyelids remain fused until much later.]]

===Lacrimal Glands===

Lacrimal glands initially develop from budding of the conjunctival epithelium near the superolateral portion of the eye. The mesenchymal cells that surround these buds are of neural crest origin, and the budding continues until the mature gland is formed.<ref><pubmed> 9882499</pubmed></ref> These glands are responsible for the production of tears however they do not start to function until 1-3 months after birth.

==Current Research==

*more info will be added soon!!

===GABA Maintains the Proliferation of Progenitors and Non-Pigmented Ciliary Epithelium===

<pubmed>22590629</pubmed>

{| width=800px
|-
| width=450px|
| width=350px|

|-
| GABA is an ‘inhibitory neurotransmitter’ in the central nervous system of adults. <ref name="PMID22590629"><pubmed>22590629</pubmed></ref> It is responsible for controlling proliferation of stem cells and progenitor cells. The authors of this article <ref name="PMID22590629"/> was interested to find the effects of GABA on proliferation of progenitor cells and non-pigmented ciliary epithelial cells (NPE) in the retina. Their study focused on progenitor cells and non-pigmented epithelium of the ciliary body in chickens. Non-pigmented epithelial cells in chickens arise from the neuroepithelium of the optic cup. They share similar functions as progenitors of the early retina, such as expression of Chx10 and Pax6 genes. It is not agreed upon whether epithelial cells of the ciliary body have stem cell properties. However, it has been found that these cells can be cultured and transplanted into retinas that are injured, in order to replace neurons that were previously lost. However, there is not much known about what factors regulate the proliferation of stem cells. Hence the authors were interested in finding the effects of GABA on proliferation of retinal cells. Their results showed that non-pigmented epithelial cells in chickens ‘express extrasynaptic-like GABAA receptors’ that have the ability to regulate cell proliferation. It has been found that inhibiting these ‘GABAA receptors’ also causes a decrease in proliferation of retinal progenitor cells and non-pigmented epithelial cells in 'the intact E8 retina’. <ref name="PMID22590629"/>

|
[[File:Gaba-effects-retina.JPG|thumbnail|250px|'''GABAA receptor mediated effects on retinal progenitor cell proliferation'''
]]
|}

-------------------

===The impact of visible light on the immature retina===

<pubmed>22405869</pubmed>

The authors mentioned in this article <ref name="PMID22405869"><pubmed>22405869</pubmed></ref> that they were interested in investigating the effect of light on postnatal eye development in mice, because mice are born with fused eyelids, which separate 12 days after birth. Before the eyelids separate, the retina develops in mice with very little radiation from light. It is believed that the darkness plays a role in the development of the retina in mice, which is why their eyelids are fused for 12 days after birth. Therefore the authors were interested to see what effect light would have on postnatal retinal development of mice, with special interest in retinal ganglion cells (RGC). In their experiment, they surgically opened the eyelids on the right eyes of some of the mice to expose them to visible light 12 hours per day, while they left some other mice in the dark after surgical separation of their eyelids. They also kept the left eyes of the mice naturally fused as controls in the experiment. Their results showed that early light exposure in mice causes a decrease in retinal ganglion cells because it affects cellular apoptosis in the retina. The authors also observed that early exposure to light in mice causes lumican mRna transcription to resume and to quickly increase. (Lumican normally stays silent in retina after birth).

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===MIP/Aquaporin 0 Represents a Direct Transcriptional Target of PITX3 in the Developing Lens===

<pubmed>21698120</pubmed>

{| width=800px
|-
|PITX3 plays a siginificant role in the development of lens in vertebrates. If there is a deficiency is PITX3, it causes a range of problems in humans such as microphthalmia, Peter’s anomaly, or isolated cataracts. Mutation of PITX3 also causes degeneration of the lens in zebrafish and mice. It is therefore important to understand what factors may affect the decrease in PITX3, as a normal level of PITX3 is needed to maintain normal eye development. The authors wanted to investigate specific genes which are affected by PITX3. Previous research has shown that MIP and Aquaporin causes defects in the lens in both mice and humans. MIP and Aquaporin are targeted by PITX3, so their imbalance is interrelated in the cause of defects in the lens. Therefore it has been previously proven that PITX3 is needed for normal development of the lens. However, there has not been much information previously known regarding the exact effect that PITX3 has, or the specific genes it targets. Since MIP and Aquaporin is common genes found in humans, mice and zebrafish, the authors <ref name="PMID21698120"><pubmed>21698120</pubmed></ref> chose to study these genes to understand the pathway that PITX3 takes and its exact involvement in the development of the lens. Their results proved that deficiency in MIP and Aquaporin indeed affects normal development of the lens, and it is indeed related to deficiency in PITX3. However, there is still more research needed to understand PITX3 and the genes it interacts with, and their effect in ocular development.

|
[[File:Mip1-expression-in-pitx3.jpg|thumbnail|250px|'''Analysis of mip1 expression in pitx3-mo and control embryos via in situ hybridization and RT-PCR''']]
|}

-----------

<pubmed>22496813</pubmed>

This research <ref name="PMID22496813"><pubmed>22496813</pubmed></ref> studied c-Jun N-terminal Kinase (JNK) activation in the retina of newborn rats

[[File:JNK1.png]]

<pubmed>20544023</pubmed>

<pubmed>20459797</pubmed>

[http://www.advancedcell.com/patients/clinical-trial-information/ Advanced Cell Technology]- A biotechnology company which is currently running two clinical trials that utilise human embryonic stem cell derived retinal pigmented epithelial cells. These trials are examining the possibility of using these cells to treat stargardt's macular dystrophy and dry age-related macular degeneration<ref><pubmed>22281388</pubmed></ref>.

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===LRP5 is required for vascular development in deeper layers of the retina===

<pubmed>20652025</pubmed>

{| width=800px
|-
|
The lipoprotein receptor-related protein 5 (LRP5) has a significant function in the development of retinal vasculature.<ref name="PMID20652025"><pubmed>20652025</pubmed></ref> Research has shown that mutations of the LRP5 causes loss of function, due to incomplete development of retinal vessel network, in both humans and mice. The authors investigated how mutations occur in the LRP5, which leads to abnormal development of the retinal vasculature. They have studied retinal endothelial cells in mutant mice in their study. Their results showed that in retina with mutated LRP5, endothelial cells in the retinal vasculature primarily produced cell clusters in the inner-plexiform layer instead of migrating into deeper layers of the retina to form normal retinal vasculature. The authors also discovered that there was a decrease in Slc38a5, which is a “a Müller cell-specific glutamine transporter”, in mice with mutated LRP5. Their results lead the authors to conclude that normal LRP5 is very important in the development of normal retinal vasculature due to their role in causing migration of retinal endothelial cells in the deeper layers of the retina. LRP5 is also important for retinal interneurons and Müller cells to function correctly.

|
[[File:Retina-cell-clusters.JPG|350px|thumbnail|'''Endothelial cells form thick clusters in the LRP5 mutant retina''']]
|}

-----------------

==Useful Links==

{{External Links}}

[http://www.youtube.com/watch?v=Xme8PA6xv-M Visualisation of eye development in the embryo]

[http://www.embryo.chronolab.com/sense.htm Embryonic Development of the eye]

==Glossary==

'''Accommodation''' - changing the focal length of the lens in order to focus on an object.

'''Downstream genes''' - genes that are activated by other "upstream genes".

'''Ectoderm''' - outermost layer of germ cells in an early embryo.

'''Endoderm''' - innermost layer of germ cells in an early embryo.

'''Glial cells''' - non-neuronal cells that provide structure and protection to neurons as well as producing myelin.

'''Inductive signaling''' - a process whereby the secretion of factors from one cell or tissue triggers a response in another.

'''Lens vesicle''' - the cavity of invaginated ectoderm from the optic placode that will form the lens.

'''Macula''' - a highly pigmented, oval-shaped area located near the centre of the retina. Important for visual acuity.

'''Mesenchyme''' - undifferentiated, loose connective tissue.

'''Mesoderm''' - middle layer of germ cells in an early embryo.

'''Mesothelium''' - the epithelial layer of the mesoderm.

'''Myelinisation''' - development of a myelin sheath around a nerve fibre.

'''Neural crest''' - a portion of the ectoderm situated next to the neural tube.

'''Neural groove''' - a large invagination on the dorsal surface of the embryo which will close off and form the neural tube.

'''Neural tube''' - hollow structure that results from the folding of the neural plate and eventually forms the central nervous system.

'''Neuroblastic layer''' - a layer of immature cells that differentiate to form either glial cells or neurons. The retina has two of these (an inner and outer).

'''Neuroectoderm''' - portion of the ectoderm that develops to form the central and peripheral nervous systems.

'''Optic chiasm''' - the point at which the optic nerves meet and cross over.

'''Optic cup''' - the structure that is formed after the optic vesicle folds in upon itself. This will form the retina.

'''Optic globe''' - a term that refers to the optic cup, lens vesicle and surrounding mesenchyme collectively.

'''Optic placode''' - area of thickened ectoderm that gives rise to the lens of the eye.

'''Optic stalk''' - a long, narrow cavity that will produce the optic nerve.

'''Optic vesicle''' - a cavity that buds off from the neural tube and gives rise to the optic cup.

'''Upstream genes''' - genes that activate one or more other "downstream genes".

'''Vascularise''' - to invade with blood vessels.

==Image Gallery==
<gallery>
Image:Eye_diagram_bandw.jpg‎ | Basic structure of the human eye.
Image:Stage14 sem2b-limb.jpg | A Stage 14 embryo showing the location of an otic placode.
Image:Stage 13 image 060.jpg | A cross section showing the organisation of the developing brain, the optic vesicle and the lens (optic) placode.
Image:Formation of the optic vesicle 1.jpg | Early formation of the optic vesicle from the neural groove.
Image:Formation of the optic vesicle 2.jpg | The optic vesicle at a later stage, showing the optic stalk.
Image:Formation of the optic nerve and chiasm 1.jpg | A recognisable brain and eye structure in later development.
Image:Formation of the optic cup 1.jpg | Mechanism of optic cup formation.
Image:Formation of the optic cup 2.jpg | Layers of the optic cup in retina development.
Image:Formation of the retina 1.jpg | Cross-section of the primitive retina showing cell types and layers.
Image:Formation of the retina 2.jpg | Cross-section of a developed retina showing cell types and layers.
Image:Formation of the lens 1.jpg | The importance of the optic cup in lens differentiation.
Image:Formation of the lens 2.jpg | The lens placode separates from the ectoderm and migrates into the mesoderm forming the lens vesicle.
Image:Formation of the choroid and sclera 1.jpg | The choroid and sclera derives from mesenchyme surrounding the optic cup.
Image:Formation of the eyelid 1.jpg | Small grooves in the ectoderm of the head - the precursors to an eyelid.
Image:Formation of the eyelid 2.jpg | The eye at an advanced stage of embryonic development. Note however, that the eyelids remain fused until much later.

</gallery>

==References==
<references/>

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--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

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{{2012Projects}}

2012 Group Project 1

2012-10-02T13:16:02Z

Z3254758: /* Iris */

[[File:Eye_collage_2.jpg|right|830px]]

=Vision Development=

==Introduction==

Eyes are an important sensory organ shared across many different species and allow organisms to gather useful visual information from their environment. The visual system uses light from the environment and processes this information in the brain for visual perception. The visual system is complex, and is made up of various structures that work together to form vision. Each of the structures in the eye have specific tasks which contribute to the visual system. Knowledge of how the eye develops extends as far back as Aristotle more than 2000 years ago, and current knowledge shows that most of the crucial events of eye development occur in the embryological stage. The eye is an interesting model for studying the development of tissues in organisms, as it consists of cells from several parts of the embryo including the head ectoderm, neural ectoderm and mesoderm. From its many origins the cells come together and differentiate to produce the complex organ that is the eye. During this period there are many examples of inductive signaling, as the tissues coordinate their development throughout this elegant process.

The main anatomical structures of the eye are as follows:
{|
|
* Cornea

* Sclera

* Choroid

* Iris

* Ciliary body

* Lens

* Anterior chamber

* Posterior chamber

* Retina

* Optic nerve

|[[File:eye_diagram_bandw.jpg|right|250px|thumb|Basic structure of the human eye.]]
|}
[[File:Eyediagramcolour1.JPG|550px]]

==Research History==

=== '''Brief Timeline of Historical Developments on the Eye and its Embryology''' ===

{| width=800px
|-bgcolor="CEDFF2"
| width=100px|'''Time'''
| width=700px|'''Discovery'''

|-bgcolor="F5FAFF"
| '''Ancient Egyptians'''
| First to document cataracts. It is described as being 'the white disease of the eye' or 'darkening of the pupil.' <ref>Edwards, D.D. (1996). Ophthalmology before Hippocrates. In the History of Ophthalmology, ed. D.M. Albert and D.D. Edwards. Cambridge, Mass.: Blackwell Science.</ref> The Egyptians had some knowledge of the eye, however it is not known how much of the anatomy of the eye was known in their era.

|-bgcolor="CEDFF2"
| '''535 BC'''

|
Ancient Greek philosopher Alcmaeon conducted dissection of humans for the first time in recorded history. This included dissection of the eye. However, not much is known about which anatomical features he discovered. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17.">Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17.</ref>

|-bgcolor="F5FAFF"
| '''384- 322 BC'''

| [[File:Aristotle-eye.jpg|200px|thumbnail|The eye according to Aristotle.<ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "> Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau </ref> Note the lens is missing, and there are three vessels drawn that was believed to transport fluid to and from the eye.<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
]]
Aristotle performed dissections of animal embryos.<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

When Aristotle described the embryo of a ten day old chicken, he wrote "The eyes about this time, if taken out, are larger than beans and black; if their skin is removed the fluid inside is white and cold, shining brightly in the light, but nothing solid." <ref name="Magnus, H. (1998). Ophthalmology of the ancients. In J. Hirschberg (Ed.), The History of Ophthalmology: The monographs, Vol. 4, Part 1 (F.C. Blodi, Trans.) Bonn: Wayenborgh.">Magnus, H. (1998). Ophthalmology of the ancients. In J. Hirschberg (Ed.), The History of Ophthalmology: The monographs, Vol. 4, Part 1 (F.C. Blodi, Trans.) Bonn: Wayenborgh.</ref>

Aristotle believed that the eyes started forming during early embryogenesis, however, he also believed that the eyes are the last organs to form completely, and he incorrectly thought that the eyes shrink in later embryonic development. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press.">Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press.</ref> .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"

| '''340 BC'''

| Lens is thought to have been discovered by Hippocrates, due to his descriptions of the contents of the internal eye There has been studies in chick development later on by followers of Hippocrates. They claimed that eyes were visible in early embryogenesis. .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
|-bgcolor="F5FAFF"
|'''25 BC - 50 AD'''

| [[File:Celsus-eye.jpg|150px|thumb|The eye according to Celsus. <ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "/>
Note the lens is placed in the centre of the eye, in the vitreous.<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> ]]

Aulus Cornelius Celsus wrote a Roman medical text called 'De Medicina' in which he wrote that the lens was the part of the eye from which vision originated. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.">Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.</ref> Celsus also incorrectly drew the lens in the center of the globe in his diagram of the eye. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

|-bgcolor="CEDFF2"
| '''23-79 AD '''
|
Pliny the Elder said that the eye is the last of the organs to develop in the womb <ref name="Magnus, H. (1998). Ophthalmology of the ancients. In J. Hirschberg (Ed.), The History of Ophthalmology: The monographs, Vol. 4, Part 1 (F.C. Blodi, Trans.) Bonn: Wayenborgh."/>
|-bgcolor="F5FAFF"
| '''98-117 AD'''

| [[File:Rufus-eye.jpg|150px|thumb|The eye according to Rufus of Ephesus. <ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "/>
Note the lens is placed in the correct position, behind the iris of the eye <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> ]]

Rufus of Ephesus identified the lens as being located in the anterior part of the eye, close to the pupil. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

His diagram illustrates that he knew the correct position of the lens as being directly behind the iris, in the anterior part of the eye, and not in the centre as was previously depicted by others before him.

|-bgcolor="CEDFF2"
| '''130-200 AD'''

| [[File:Galen-eye1.jpg|150px|thumb|The eye according to Galen. <ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "/> ]]

Claudius Galen practised medicine in Rome. He wrote:

"1. Within the eye the principal orgran of sensation is the crystalline lens.

2. The sensation potential comes from the brain and is conducted via the optic nerves.

3. All other parts of the eyeball are supporting structures." <ref> Hirschberge, J. (1982). Antiquity, Vol. X in the History of Ophthalmology (F.C. Blodi, Trans.) Bonn: Wayenborgh. pp. 280 </ref>

Galen thought that the lens was produced from the vitreous. He also believed that the retina’s function was to give nourishment to the lens and vitreous, and to carry visual information to the brain from the lens. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

|-bgcolor="F5FAFF"

| '''1514-1564'''

| Andreas Vesalius published his anatomy book "De Humani Corporis Fabrica in 1543. He had the misconception that the lens was located in the centre of the eyeball. .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> He also wrote that the lens functioned "like a convex lens made of glass" <ref name="Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.">Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.</ref> pp. 48
|-bgcolor="CEDFF2"
| '''1535-1606'''

| Georg Bartisch correctly drew a diagram of the lens placed behind the iris in his book 'Ophthalmodouleia: das ist Augendienst'. <ref name="Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>
|-bgcolor="F5FAFF"

| '''1537-1619'''

| Fallopio Hieronymus Fabricius ab Aquapendente studied anatomy and embryology. He studied chicken embryos, and thought that chalazae (which comes from egg white) gives rise to the eyes. He also drew the lens directly behind the iris in a diagram in is book 'Tractatus de Oculo Visuque Organo. <ref name="Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

|-bgcolor="CEDFF2"
| '''1583'''

| Felix Platter published his book 'De corporis Humani Structura et Usu, after he performed dissections of human bodies. He believed that the retina is the primary visual organ in the eye. .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="F5FAFF"
| '''1619'''
| Scheiner is given credit to be the first person to correctly draw the diagram of the anatomy of the eye. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
|-bgcolor="CEDFF2"
| '''1672'''
| Marcello Malpighi described the embryonic development of the chicken. He drew many detailed diagrams of the chick eye. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1665'''
| Nicolaus Steno identified the choroid fissure in his study of a developing embryo of a chicken. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="CEDFF2"
| '''1754'''

| Albrecht von Haller studied the embryology of the eye. With help from his student Johann Gottfried Zinn, he contributed to the understanding of the development of the ciliary body, ciliary zonule, and their relationship with the lens and vitreous. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1817'''

| Christian Pander discovered the three embryonic germ layers, which he wrote about in his book. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/> Pander was the first to think of 'the optic vesicles as lateral evaginations' of the 'prosencephalon'; however, he was incorrect about the details regarding how 'the eye develops from these evaginations'. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="CEDFF2"
| '''1828-1837'''

| Karl Ernst von Baer studied embryology. He discovered that the optic vesicles were 'outgrowths of the embryonic forebrain' <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> which he believed was caused by pressure from fluids in the central nervous system. Von Baer also believed that the optic vesicle opens to form the pupil, and that fluid in the optic vesicle coagulates to form the vitreous body and lens. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1830'''

| Emil Huschke discovered that the lens forms from the invagination of the surface ectoderm. He concluded that the lens hence does not form ‘from the fluid of the optic vesicle’ <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> as previously thought.
|-bgcolor="CEDFF2"
| '''1832'''

| Emil Huschke wrote in his manuscript ‘Ueber die erste Entwinkenlung des Auges und die damit zusammenhängende Cyklopie’ that the lens capsule forms from the outer surface ectoderm, which detaches and moves back inward, which is later enclosed again by several membranes, such as by the cornea. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

Huschke also described how the optic cup and choroid fissure forms. He discovered that the optic vesicles are produced from the two-layered optic cup. However, he incorrectly described the destiny of the ‘individual optic cup layers’. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

|-bgcolor="F5FAFF"
| '''1838'''
| Matthias Jakob Schleiden and Theodor Schwann formulated the ‘cell theory’: “All living things are formed from cells, the cell is the smallest unit of life, and cells arise from pre-existing cells.” <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
|-bgcolor="CEDFF2"
| '''1839'''

| Theodor Schwann contributed a better understanding of the development of the lens through studying the foetus of a pig, which he wrote about in his book ‘Mikroskopische Untersuchungen Über Die Uebereinstimmung in Der Struktur Und Dem Wachsthum Der Thiere Und Pflanzen’. He wrote that the lens is made of ‘concentric layers’ of fibres which proceeds from an anterior to posterior direction. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1842'''
| Robert Remak gave the current names to the three embryonic germ layers: ectoderm, mesoderm and endoderm. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"
| '''1843'''
| Wilhelm Werneck published his book ‘Beiträge zur Gewebelehre des Kristallkörpers’. He wrote that the contents inside of the lens is not made of fluids, as was previously believed. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/> Werneck also discovered that the fibers of the lens continues to grow from the outside to the centre during embryogenesis. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

|-bgcolor="F5FAFF"
| '''1855'''

| Robert Remak wrote his book ‘Untersuchungen über die Entwickelung der Wirbelthiere’. He wrote about what he discovered in his studies of the development of the eye in the embryos of chickens, frogs, and rabbits. He wrote very descriptively about the embryology of lens formation, amongst other topics. He discovered that the ectoderm gives rise to the lens placode. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

|-bgcolor="CEDFF2"
| '''1858'''
| Henry Gray published his book 'Anatomy, Descriptive and Surgical'. He had also previously studied the embryonic development of the optic nerve and retina of chickens.
|-bgcolor="F5FAFF"
| '''1877'''
| Paul Leonhard Kessler wrote about the embryonic development of the lens in mice in his book ‘Zur Entwickelung des Auges der Wirbelthiere. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"
| '''1891'''
| Vincenzo Colucci studied newts and discovered their ability to regenerate the lens.<ref> Tsonis, P. A. (2001). Regeneration of the Vertebrate Lens and Other Eye Structures. eLS. (Online Publication). DOI: 10.1038/npg.els.0001102 </ref>
|-bgcolor="F5FAFF"
| '''1892'''
| Dr. Oscar Hertwig published his book ‘Text-Book of the Embryology of Man and Mammals. <ref> Hertwig, O. Text-book of the embryology of man and mammals. S. Sonnenschein 1901. (Translated from the 3d German ed. by Edward L. Mark.) </ref> It contains a very detailed description of the development of the eye, according to the findings at that time. [http://embryology.med.unsw.edu.au/embryology/index.php?title=Book_-_Text-Book_of_the_Embryology_of_Man_and_Mammals_16-2#The_Development_of_the_Eye]
|-bgcolor="CEDFF2"
| '''1895'''
| Gustav Wolff also independently studied newts and discovered their ability to regenerate the lens. .<ref> Tsonis, P. A. (2001). Regeneration of the Vertebrate Lens and Other Eye Structures. eLS. (Online Publication). DOI: 10.1038/npg.els.0001102 </ref>

|-bgcolor="F5FAFF"

| '''1900'''
| Carl Rabl published his book ‘Uber den Bau und die Entwicklung der Linse’. He wrote about the development of the lens in mammals, fish, birds, reptiles, and amphibians. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"
| '''1901'''
| Hans Spemann published his findings from his experimental studies about the formation of the lens in the frog. He found that the optic cup needed to be in contact with the ectoderm for normal development of the eye. <ref> Spemann, H. (1901). Über Correlationen in der Entwicklung des Auges. Verhand. Anat. Ges. 15: 61-79. </ref> <ref> Saha, M. (1991). Spemann seen through a lens. In Gilbert, S. F. (ed.). A Conceptual History of Modern Embryology. Plenum Press, NY. pp. 91-108.</ref>
|-bgcolor="F5FAFF"
| '''1906'''
| Brown ‘s book “The Embryology Anatomy and Histology of the Eye” was published. It contained detailed descriptions of the embryonic development of the eye according to the knowledge current at that time, mainly based on observations from embryos of rabbits and chickens. <ref> Brown, E.J. (1906). The Embryology Anatomy and Histology of the Eye. Chicago: Hazlitt & Walker. 1906 </ref>

|-bgcolor="CEDFF2"
| '''1907'''

| John Clement Heisler published his book ‘A Text-book of embryology’. It contains a chapter detailing the embryonic development of the eye, according to the knowledge current at that time. The book’s copyright has expired, so it can be viewed free online: [http://archive.org/details/atextbookembryo01heisgoog]

Julius Kollman also published his book 'Atlas of the Development of Man'. It contained very detailed description and illustrations showing the embryonic development of the human according to the knowledge current at that time. His illustrations were reused by many others after his time and built upon for further refined understanding of the embryology of the human.

Here are examples of Julius Kollman's excellent illustrations showing eye development in various stages:

'''Formation of Primary Optic Vesicle:'''
<gallery>
File:Kollmann691.jpg|The blue part at the bottom is the endoderm. The pink middle layer is the mesoderm. The top yellow layer is the ectoderm. The fold labelled as 'augenfeld' is the place where the optic vesicle will form.
File:Kollmann692.jpg|The eye area (augenfeld) is a bowl shaped bulge still located on the side walls.
File:Kollmann693.jpg| The neural tube is shown after removal of all of the ectoderm and ventral organs, such as heart, gut tube, etc. The primary optic vesicle forms a slightly flattened hollow protrusion on the forebrain.
File:Kollmann694.jpg|The lateral surface of the primary optic vesicle is slightly depressed, showing the first sign of the emergence of the secondary optic vesicle
</gallery>

'''Development of Lens:'''

<gallery>
File:Kollmann695.jpg|The bulging lateral wall of the primary optic vesicle is covered by a fairly well demarcated lens plate, a direct continuation of the ectoderm. Between the optic vesicle and the lens pit are some flattened spindle-shaped cells. In the adjoining mesoderm are cross-sections of capillaries.
File:Kollmann697.jpg|The lens still hangs together with the ectoderm. The primary eye vesicle is indented with respect to the lens. Between the lens and the lateral plate of the optic vesicle is a narrow space, which allows area to further develop later.
File:Kollmann698.jpg|4th Week of development. The internal organisation shows the secondary optic vesicle. A: The rear wall of lens is noticeable and is enveloped by mesoderm. B: The edges of the lens pit is already grown and the lens vesicles are formed, which is still related to the remaining ectoderm.
File:Kollmann699.jpg|The lens has now cut off from the ectoderm, but is still very superficial. Between it and the lateral lamina of the optic cup, there is a considerable space. The eye stalk has become longer and is enclosed together with the optic cup and lens of the mesoderm. The cornea, sclera and choroid make gradual development.
</gallery>

|-bgcolor="F5FAFF"

| '''1921'''
| Bailey and Miller published their textbook “Text-Book of Embryology “. <ref> Bailey, F.R. and Miller, A.M. (1921). Text-Book of Embryology. New York: William Wood and Co. (Note- This book is only at an early edited stage)</ref> It contains detailed description of the development of the embryonic eye according to the knowledge current at that time. [http://embryology.med.unsw.edu.au/embryology/index.php?title=Book_-_Text-Book_of_Embryology_18]

|-bgcolor="CEDFF2"
| '''1925'''

| Mann published his research article, in which he gives a detailed account of the development of the human iris. He divided the development of the iris into four stages: weeks 4-7 (before the ectodermal iris forms or before the anterior chamber forms); weeks 7-11 (anterior chamber appears, and mesodermal iris forms); weeks 11-12 (ectodermal iris forms); 3-8 months (muscles of the pupil forms from ectodermal iris, and the central portion of the mesodermal iris atrophies to make the pupil clear). <ref name="PMID18168466"><pubmed>18168466</pubmed></ref>
O Leser also published an article detailing the development of extraocular muscles in mammals he studied. <ref name="PMID18168498"><pubmed>18168498</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1939'''
| Holtfreter <ref> Holtfreter, J. (1939). Gewebeaffinitat, ein Mittel der embryonalen
Formbildung. Arch. Exp. Zellforsch. 23, 169-209. </ref> studied amphibians and observed that that the development of the eye stops at the ‘optic vesicle stage’ if there is no contact ‘with the epidermis and neural crest driven mesenchyme’. <ref name=”PMID11023863”><pubmed>11023863</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1955'''
| Barber published his book ‘Embryology of the human eye’. <ref> Barber AN: Embryology of the human eye. St. Louis. CV Mosby 1955</ref> In contains detailed descriptions of the embryological development of the human eye according to the knowledge current at that time. It contains many photographs of the eye at different stages of development.

|-bgcolor="F5FAFF"
| '''1957'''
| Coulombre studied a chicken embryo to find the role of intraocular pressure in the development of the chick’s eye, especially in regards to its control of the size of the eye structures. <ref name="PMID13469954"><pubmed>13469954</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1958'''
| Coulombre studied the development of the cornea and how it develops its transparency. <ref name="PMID13563560"><pubmed>13563560</pubmed></ref> He also studied the development of corneal curvature. <ref name="PMID 13519969"><pubmed> 13519969</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1962'''
| Coulombre studied the development of the conjunctival papillae and scleral ossicles. <ref name="PMID 14023393"><pubmed> 14023393</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1963'''
| Coulombre studied the development of lens fibers and their orientation. <ref name="PMID14077035"><pubmed>14077035</pubmed></ref> He also studied the development of pigmented epithelium. <ref name="PMID14023394"><pubmed>14023394</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1964'''

| Coulombre further studied the development of the lens to determine the role of the lens in eye growth. <ref name="PMID14189921"><pubmed>14189921</pubmed></ref> He also studied the role of thyroid in the development of the cornea and the development of corneal transparency. <ref name="PMID14211912"><pubmed>14211912</pubmed></ref> Mann also published his work called ‘The development of the human eye’, which contains detailed description of the embryonic development of the eye according to current knowledge at that time. <ref> Mann I. The development of the human eye. New York: Grune and Stratton 1964</ref>

|-bgcolor="CEDFF2"
| '''1965'''
| Coulombre published his findings regarding the regeneration of the neural retina from pigmented epithelium in the embryo of chickens. <ref name="PMID5833111"><pubmed>5833111</pubmed></ref> Smelser also published his findings on the embryological development and morphology of the lens. <ref name="PMID14340157"><pubmed>14340157</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1966'''

| Formation of the face and orbit occurs from the differentiation of neural crest cells. <ref name="PMID5969670"><pubmed>5969670</pubmed></ref> O’Rahilly also published findings of the development of the eye in the early stages of human embryos. <ref> O'Rahilly, R. 1966 The early development of the eye in staged human embryos. Contr. Embry. Carnegie Inst., Wash., 38: 1–42</ref>

|-bgcolor="CEDFF2"
| '''1968'''
| Findings of the postnatal development of the retina of rats was published. <ref name="PMID5640327"><pubmed>5640327</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1969'''

| Mann again published his work called ‘The development of the human eye’. He stated that that the lens in humans forms completely from the ectoderm. <ref name=”Mann I. The Development of the Human Eye. New York, USA: Grune & Stratton, Inc; 1969”> Mann I. The Development of the Human Eye. New York, USA: Grune & Stratton, Inc; 1969</ref> Coulombre also studied the development of the lens, and took note of its size, shape and orientation throughout its developmental stages. <ref name="PMID 5772716"><pubmed> 5772716</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1970'''
| Coulombre again further studied the regeneration of the neural retina from pigmented epithelium of embryos of chickens. <ref name="PMID 5472476"><pubmed> 5472476</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1971'''

| Coulombre further studied the development of the lens. This time he focused on analysing the histological mechanisms in the reconstitution of the lens from implanted lens epithelium. <ref name="PMID 4925671"><pubmed> 4925671</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1973'''
| A research article was published, detailing the embryonic development of the retina of humans. <ref name="PMID 6650859"><pubmed> 6650859</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1976'''

| Geeraets published his observations of the closure of the embryonic optic fissure in golden hamsters, using the electron microscope. <ref name="PMID 1266776"><pubmed> 1266776</pubmed></ref> Kornneef also published an article based on his studies of the development of connective tissue in the human orbit. <ref name="PMID 1020699"><pubmed> 1020699</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1981'''
| A research article was published detailing how myelin forms in the optic nerve of humans. <ref name="PMID 7224936"><pubmed> 7224936</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1983'''
| O’Rahilly’s further research developments was published, reporting the timing and sequence of events in the development of the embryonic human eye. <ref name="PMID 6650859"><pubmed> 6650859</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1990'''

| Van Driell et al. <ref>Driell, D. Van; Provis, J.M.; Billson, F.A.: Early differentiation of ganglion, amacrine, bipolar and Muller cells in the developing fovea of the human retina. J. Comp. Neurol. 291: 203-219.</ref> studied the manner in which amacrine, bipolar, retinal ganglion cells, and Muller cells differentiate in the developing fovea of the retina of a 15-week old human foetus. <ref name="PMID1628748"><pubmed>1628748</pubmed></ref> Tripathy also published an article providing evidence that the lacrimal glands in humans originates from the neuroectoderm. <ref name="PMID2406219"><pubmed>2406219</pubmed></ref>

|}

==Development, Structure and Function of Ocular Components==

The eye itself is formed from several components; notably the optic placode of the head ectoderm, the optic vesicle from the neural tube, and mesenchyme from the mesoderm and neural crest cells. The optic placode contributes the lens to the eye, the optic vesicle gives rise to layers of the retina, while the mesenchyme will produce the ciliary body, iris, choroid and sclera.<ref>http://www.vetmed.vt.edu/education/curriculum/vm8054/eye/EMBYEYE.HTM</ref> Cells from the neural tube will also produce the optic nerve, which receives nerve impulses from the retina of the eye. Eyes initially form as laterally paired structures and migrate medially in the human embryo. In other animals such as birds and lizards, the eyes do not migrate and develop laterally on the head. The optic placodes become prominent on the surface of the embryo at approximately Stage 14 of development.

[[File:Stage14 sem2b-limb.jpg|200px|thumb|left|A Stage 14 embryo showing the location of an otic placode.<ref name="http://embryology.med.unsw.edu.au/embryology/index.php?title=ANAT2341_Lab_6_-_Early_Embryo">http://embryology.med.unsw.edu.au/embryology/index.php?title=ANAT2341_Lab_6_-_Early_Embryo</ref>]] [[File:Stage 13 image 060.jpg|400px|thumb|center|A cross section showing the organisation of the developing brain, the optic vesicle and the lens (optic) placode.<ref name="http://embryology.med.unsw.edu.au/embryology/index.php?title=ANAT2341_Lab_6_-_Early_Embryo"/>]]

===Optic Nerve===

The optic nerve consists of nerve fibres that transmit information from the retinal photoreceptor cells to the brain. The optic nerve is formed from the optic stalk, which develops as the optic vesicle migrates from its origin in the neural tube to its destination - the surface ectoderm - where it will fuse with the optic placode (also known as the lens placode, which will contribute the lens to the eye).<ref name="PMID11687490"><pubmed>11687490</pubmed></ref>

[[File:Formation of the optic vesicle 1.jpg|400px|thumb|left|Fig. 1: Early formation of the optic vesicle from the neural groove.]] [[File:Formation of the optic vesicle 2.jpg|400px|thumb|center|Fig. 2: The optic vesicle at a later stage, showing the optic stalk.]]

As can be seen in Figure 1 above, the optic vesicle forms from the neural tube. However, note that the neural tube has not yet closed, and is still the neural groove at this point. Figure 2 then shows the optic vesicle at slightly later stage in the same simplified cross-section of the embryo, as it migrates from the neural tube to the surface ectoderm. Note the presence of the optic stalk which links the optic vesicle to the neural tube. Later in development, this primitive structure will become the optic nerve, which will link the eye to the brain.

The nerve fibres themselves will initially originate from the retinal ganglion cells in the eye during week 6.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008">Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008</ref> After two weeks, these fibers will have grown along the inner wall of the optic stalk and have reached the brain. They grow both in length and width, with the nerve fibres filling the hollow optic stalk to form the solid optic nerve. More than one million nerve fibers will eventually make up the optic nerve, along with glial cells which arise from the inner wall of the optic stalk itself.<ref><pubmed>1451666</pubmed></ref> Myelinisation of the optic nerve begins much later in development at around 7 months, beginning at the optic chiasm and moving towards the eye.<ref><pubmed>7224936</pubmed></ref> The optic chiasm forms just before the nerves reach the brain, and is where half the nerve fibres from each eye will cross over to the opposite side of the brain. This is demonstrated in Figure 3. Note the crossing over of the optic nerves just before they enter the brain, at the optic chiasm. This organisation is now much more familiar, with the eyes near the ectoderm and the optic nerve leading through the mesoderm to the brain buried deep in the embryo.

[[File:Formation of the optic nerve and chiasm 1.jpg|400px|thumb|center|Fig. 3: A recognisable brain and eye structure in later development.]]

===Retina===

The retinal component of the eye is formed when the optic vesicle folds in upon itself, forming the optic cup (see Figure 4). In doing so it creates two layers - an inner wall and an outer wall of the optic cup (Figure 5). These two layers of the optic cup will give rise to the two layers of the retina - the inner neural retina, and the outer pigmented epithelium.<ref name="PMID11687490"/> Note the existence of the space between the two layers of the retina. This is known as the intraretinal space and disappears by the 7th week of development, however the two layers never completely fuse and can become separated as a result of physical trauma to the head - leading to a detached retina and loss of vision.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/>

The inner wall of the optic cup, which will give rise to the neural retina, consists of a layer of pseudostratified cells (see Figure 6) that later differentiate into rod, cone, bipolar, ganglion, horizontal, amacrine and glial cells of the retina (Figure 7).<ref name="PMID18168748"><pubmed>18168748</pubmed></ref> The outer wall of the optic cup consists of a layer of cuboidal cells that contain melanin - the light absorbing pigment. The function of this layer is to absorb light and prevent internal reflection of light within the eye, which would impair our ability to form distinct images. Interestingly, in some animals such as cats, this layer actually reflects light intentionally to increase the amount of light available to the eye in low-light conditions. This is why cats seem to have eyes that glow in the dark.<ref>http://dialspace.dial.pipex.com/agarman/bco/fact4.htm</ref>

[[File:Formation of the optic cup 1.jpg|400px|thumb|left|Fig. 4: Mechanism of optic cup formation.]] [[File:Formation of the optic cup 2.jpg|400px|thumb|center|Fig. 5: Layers of the optic cup in retina development.]]

The inner wall itself is divided into two components - the inner neuroblastic layer and the outer neuroblastic layer (see Figure 6). The outer neuroblastic layer forms the rod and cone cells while the inner neuroblastic layer forms the remaining cell types found in the retina - the bipolar, ganglion, horizontal, amacrine and glial cells (Figure 7).<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/> The organisation of the retina is interesting in that incoming light passes through several layers of these neural retina cells before it is detected by rod and cone cells at the back of the retina, and then nerve signals are passed back through the layers of neural retina cells that the light just passed through moments before - a seemingly strange design that the eye does not share with man-made light-capturing devices such as a camera (imagine putting the wires in front of the image sensor!).

Differentiation of the neuroblastic layers into neural retina cells occurs in a pattern both within the layers and across the retina. Cells differentiate from the inner neuroblastic layer to the outer neuroblastic layer, and differentiate from the central retina to the peripheral retina.<ref name="PMID18168748"/> The macula is first identifiable in week 22 when ganglion cells start to form multiple rows, and the primitive fovea begins to form at approximately the same time as a depression in the macula.<ref><pubmed>6462623</pubmed></ref> It is not until 15-45 months after birth that this area becomes exclusively populated by cone cells and becomes the fovea centralis - the area of the retina with the highest visual acuity.

[[File:Formation of the retina 1.jpg|400px|thumb|left|Fig. 6: Cross-section of the primitive retina showing cell types and layers.]] [[File:Formation of the retina 2.jpg|400px|thumb|center|Fig. 7:Cross-section of a developed retina showing cell types and layers.]]

===Ciliary Body===

The ciliary body consists of ciliary processes and three portions of fibres that constitute the ciliary muscles. It functions to maintain normal eye physiology as well as playing a direct role in accommodation.

During development, the ciliary processes form slightly posterior to the iris, developing from part of the anterior rim of the optic cup. It is thought that the folded structure of the ciliary processes is brought about by intraocular pressure and specific signalling pathways.<ref name="PMID16959249"><pubmed>16959249</pubmed></ref> While the ciliary muscles and the endothelial cells of the ciliary blood vessels are chiefly formed by mesenchymal cells<ref><pubmed>16249499</pubmed></ref>, the neural crest and neuroectoderm also contribute to their development.<ref><pubmed>12127103</pubmed></ref> The normal development of the ciliary body is dependent on the correct expression of bone morphogenetic protein (BMP)-4, which is a member of the transforming growth factor-β superfamily.<ref><pubmed>1222340</pubmed></ref> Napier and Kidson (2007) summarised numerous genes that have been associated with ciliary body development, however their direct roles have not been well documented.<ref name="PMID16959249"/>

===Iris===

The iris is a thin layer that develops at the end of the third month of development and is derived from the anterior rim of the optic cup. The stroma of the iris develops from cells of neural crest cell origin.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/> The muscles that are responsible for the dilation and constriction of the pupil (dilator pupillae and sphincter pupillae muscles) form from the neuroectoderm of the optic cup. These cells are initially epithelial cells that then transform into smooth muscle cells. <ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"></ref>. The invagination of the optic vesicle which creates the optic cup, also causes the formation of the optic cup lip. This is the region of the where the epithelium doubles back, separating the outer pigmented layer and the inner nonpigmented layer. This is the edge of the iris that borders on the pupil<ref><pubmed> Retinal and anterior eye compartments derive from a common progenitor pool in the avian optic cup</pubmed></ref>.

The final colour of the iris is not evident until the postnatal period. It is determined by a number of genes including IRF4, SLC24A4 and MATP<ref><pubmed>19710684</pubmed></ref>. Other features such as crypt frequency, furrow contractions, presence of peripupillary pigmented ring, and number of nevi also become evident during development<ref><pubmed>21835309</pubmed></ref>.

Mutations in Pax6 have been shown to cause partial or complete loss of the iris <ref><pubmed>12386935</pubmed></ref>.

===Lens===

The lens has its origin from the optic placode, which develops on the ectodermic surface of the embryo and migrates both medially and inwards into the embryo. The lens allows accommodation of the eye, and adjusts its thickness in order to focus on near or far objects. The study of lens development was one of the first to highlight the importance of inductive signaling in development, with Spemann's pioneering work at the start of the 20th century, finding that the absence of retinal development resulted in the absence of lens formation.<ref name="PMID11687490"/> Indeed, it has been consistently shown that the interaction of the migrating optic vesicle with the surface ectoderm of the head is vital in producing differentiation of the lens.<ref name="PMID15558475"><pubmed>15558475</pubmed></ref> The mechanism of interaction is complex but basically involves upstream genes switching on downstream genes, with the genes eventually producing specialised proteins which constitute the lens. The whole process starts with the signaling molecules from the optic cup initiating a thickening of the surface ectoderm of the head (Figure 8). It is thought that this region of specific ectoderm is responsive to the signaling molecules, as lens formation is incomplete or absent when ectoderm from the lateral portion of the embryo (i.e. non-head ectoderm) is exposed to the same inductive signaling processes.<ref name="PMID9216064"><pubmed>9216064</pubmed></ref> Pax6 has been shown to be one of the major genes required for differentiation of the lens, which in turn switches on transcriptional genes such as Sox 1, 2 and 3 among others - producing water-soluble proteins called crystallins - responsible for giving the lens its transparency and refractive properties.<ref name="PMID9609835"><pubmed>9609835</pubmed></ref>

[[File:Formation of the lens 1.jpg|400px|thumb|left|Fig. 8: The importance of the optic cup in lens differentiation.]] [[File:Formation of the lens 2.jpg|400px|thumb|center|Fig. 9: The lens placode separates from the ectoderm and migrates into the mesoderm forming the lens vesicle.]]

The lens placode invaginates from the head ectoderm and migrates into the mesoderm (Figure 9). Once this structure (now known as the lens vesicle) is in place opposite the optic cup, the combined structure is referred to as the optic globe and resembles a recognisable eye structure. The lens continues to differentiate further, as mentioned above, through the formation of crystallin proteins, which give the lens its unique properties and allows for the fine control over the degree of refraction that takes place.

===Aqueous Chambers===

There are both anterior and posterior aqueous chambers of the eye which contain aqueous humour. A space develops in the mesenchyme situated between the lens and cornea to form the anterior aqueous chamber. The mesenchyme located superficially to this chamber forms the mesothelium as well as the transparent portion of the cornea.

The posterior chamber develops from a similar space in the mesenchyme, however it is located between the iris and the lens. The anterior and posterior chambers are able to communicate with one another once the papillary membrane vanishes and the pupil is formed. This channel is known as the scleral venous sinus.<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011">Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011</ref>

===Cornea===

The cornea is the transparent, avascular, most anterior portion of the eye. It is responsible for conducting light into the eye and focusing it on to the retina, as well as maintaining the rigidity of the eyeball. It consists of 5 layers- the epithelium, Bowman’s layer, stroma, Descemet’s membrane and the endothelium.

The epithelium and endothelium of the cornea first appear during the 5th week of gestation. The epithelium of the external surface of the cornea is derived from surface ectoderm, while the mesenchyme is derived from the mesoderm<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"/>. The endothelium is a two-cell cuboidal layer which is made up of differentiated neural crest cells that were initially from the optic cup. By week 8 the endothelial cells begin to secrete a basement membrance which later forms Descemet’s membrane<ref><pubmed>6511224</pubmed></ref>. At approximately 16 weeks gestation the Bowman’s membrane begins to form from the thickening of the stroma that is located under the corneal epithelium<ref>Riordan-Eva P, Whitcher JP. Vaughn and Asbury's General Ophthalmology, Lange Medical Books/McGraw Hill. 2004:25–27</ref>. During the third month glycosaminoglycans secreted by fibroblasts form the ground substance of the cornea, with collagen fibrils and keratan sulphate also appearing around this time. Shortly after this tight junctions form between the endothelial cells<ref><pubmed>19481138</pubmed></ref>. Towards the end of the gestational period the cornea becomes larger due to the production of aqueous humor<ref>Yanoff M, Duker JS. Ophthalmology. Mosby; St. Louis, MO: 2004</ref>. The final transparent structure develops because hyaluronidase removes hyaluronic acid, thyroxine causes dehydration of the stroma, and the entire structure becomes avascular<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/>. Numerous genes have been implicated in the development of the cornea, these include, but are not limited to, PAX6, PITX2, FOXC1, MAF, TMEM114, SOX2, OTX2 and BMP4<ref><pubmed>18637741</pubmed></ref>.

===Choroid and Sclera===

The choroid and sclera are adjacent layers that surround the eye and act to vascularise and protect the eye respectively. They are formed from neural crest and mesoderm-derived mesenchyme which condenses around the optic cup and lens vesicle between weeks 5 and 7 of development to form a primitive eyeball structure known as the optic globe.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/> Blood vessels first start to appear in the choroid layer at approximately week 15, and arteries and veins can be distinguished by week 23.<ref>Development of the Choroid and Related Structures, K. Sellheyer, Eye (1990) 4, 255-261</ref> Inductive processes are thought to play a vital role during formation of the choroid and sclera; with the retinal pigmented epithelium inducing differentiation of the surrounding mesenchyme while at the same time the neural crest-derived mesenchyme contributing components to the retinal pigmented epithelium such as melanocytes.<ref name="PMID1628748"/> In addition to having functional roles themselves, the primitive choroid and sclera also contribute components to the developing ciliary body and cornea (Figure 10). In the adult eye, the choroid is continuous with the ciliary body and the sclera with the cornea.

[[File:Formation of the choroid and sclera 1.jpg|400px|thumb|center|Fig. 10: The choroid and sclera derives from mesenchyme surrounding the optic cup.]]

===Eyelids===

The eyelids are ectodermal and mesodermal in origin and are an extension of the skin which covers and protects the eye. Eyelid formation can be first noted during week 5 when small grooves develop in the surface ectoderm (Figure 11).<ref><pubmed>7364662</pubmed></ref> These small grooves deepen and extend into the mesoderm and the primitive eyelid structures grow towards one another, eventually fusing together during week 8.<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"/> It is not until week 26-28 that the eyelids will separate again. The ectoderm reflects over the developing cornea to form the conjunctival sac, a space that is filled by secretions from the lacrimal gland in order to allow smooth motions of the eyelid over the eye and also to clean the cornea and prevent accumulation of particles on the eye that may disrupt vision. By the time the eyelids separate, the eye has all its major components present (Figure 12), and further development consists mainly of growth and vascularisation.

[[File:Formation of the eyelid 1.jpg|400px|thumb|left|Fig.11: Small grooves in the ectoderm of the head - the precursors to an eyelid.]] [[File:Formation of the eyelid 2.jpg|400px|thumb|center|Fig. 12: The eye at an advanced stage of embryonic development. Note however, that the eyelids remain fused until much later.]]

===Lacrimal Glands===

Lacrimal glands initially develop from budding of the conjunctival epithelium near the superolateral portion of the eye. The mesenchymal cells that surround these buds are of neural crest origin, and the budding continues until the mature gland is formed.<ref><pubmed> 9882499</pubmed></ref> These glands are responsible for the production of tears however they do not start to function until 1-3 months after birth.

==Current Research==

*more info will be added soon!!

===GABA Maintains the Proliferation of Progenitors and Non-Pigmented Ciliary Epithelium===

<pubmed>22590629</pubmed>

{| width=800px
|-
| width=450px|
| width=350px|

|-
| GABA is an ‘inhibitory neurotransmitter’ in the central nervous system of adults. <ref name="PMID22590629"><pubmed>22590629</pubmed></ref> It is responsible for controlling proliferation of stem cells and progenitor cells. The authors of this article <ref name="PMID22590629"/> was interested to find the effects of GABA on proliferation of progenitor cells and non-pigmented ciliary epithelial cells (NPE) in the retina. Their study focused on progenitor cells and non-pigmented epithelium of the ciliary body in chickens. Non-pigmented epithelial cells in chickens arise from the neuroepithelium of the optic cup. They share similar functions as progenitors of the early retina, such as expression of Chx10 and Pax6 genes. It is not agreed upon whether epithelial cells of the ciliary body have stem cell properties. However, it has been found that these cells can be cultured and transplanted into retinas that are injured, in order to replace neurons that were previously lost. However, there is not much known about what factors regulate the proliferation of stem cells. Hence the authors were interested in finding the effects of GABA on proliferation of retinal cells. Their results showed that non-pigmented epithelial cells in chickens ‘express extrasynaptic-like GABAA receptors’ that have the ability to regulate cell proliferation. It has been found that inhibiting these ‘GABAA receptors’ also causes a decrease in proliferation of retinal progenitor cells and non-pigmented epithelial cells in 'the intact E8 retina’. <ref name="PMID22590629"/>

|
[[File:Gaba-effects-retina.JPG|thumbnail|250px|'''GABAA receptor mediated effects on retinal progenitor cell proliferation'''
]]
|}

-------------------

===The impact of visible light on the immature retina===

<pubmed>22405869</pubmed>

The authors mentioned in this article <ref name="PMID22405869"><pubmed>22405869</pubmed></ref> that they were interested in investigating the effect of light on postnatal eye development in mice, because mice are born with fused eyelids, which separate 12 days after birth. Before the eyelids separate, the retina develops in mice with very little radiation from light. It is believed that the darkness plays a role in the development of the retina in mice, which is why their eyelids are fused for 12 days after birth. Therefore the authors were interested to see what effect light would have on postnatal retinal development of mice, with special interest in retinal ganglion cells (RGC). In their experiment, they surgically opened the eyelids on the right eyes of some of the mice to expose them to visible light 12 hours per day, while they left some other mice in the dark after surgical separation of their eyelids. They also kept the left eyes of the mice naturally fused as controls in the experiment. Their results showed that early light exposure in mice causes a decrease in retinal ganglion cells because it affects cellular apoptosis in the retina. The authors also observed that early exposure to light in mice causes lumican mRna transcription to resume and to quickly increase. (Lumican normally stays silent in retina after birth).

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===MIP/Aquaporin 0 Represents a Direct Transcriptional Target of PITX3 in the Developing Lens===

<pubmed>21698120</pubmed>

{| width=800px
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|PITX3 plays a siginificant role in the development of lens in vertebrates. If there is a deficiency is PITX3, it causes a range of problems in humans such as microphthalmia, Peter’s anomaly, or isolated cataracts. Mutation of PITX3 also causes degeneration of the lens in zebrafish and mice. It is therefore important to understand what factors may affect the decrease in PITX3, as a normal level of PITX3 is needed to maintain normal eye development. The authors wanted to investigate specific genes which are affected by PITX3. Previous research has shown that MIP and Aquaporin causes defects in the lens in both mice and humans. MIP and Aquaporin are targeted by PITX3, so their imbalance is interrelated in the cause of defects in the lens. Therefore it has been previously proven that PITX3 is needed for normal development of the lens. However, there has not been much information previously known regarding the exact effect that PITX3 has, or the specific genes it targets. Since MIP and Aquaporin is common genes found in humans, mice and zebrafish, the authors <ref name="PMID21698120"><pubmed>21698120</pubmed></ref> chose to study these genes to understand the pathway that PITX3 takes and its exact involvement in the development of the lens. Their results proved that deficiency in MIP and Aquaporin indeed affects normal development of the lens, and it is indeed related to deficiency in PITX3. However, there is still more research needed to understand PITX3 and the genes it interacts with, and their effect in ocular development.

|
[[File:Mip1-expression-in-pitx3.jpg|thumbnail|250px|'''Analysis of mip1 expression in pitx3-mo and control embryos via in situ hybridization and RT-PCR''']]
|}

-----------

<pubmed>22496813</pubmed>

This research <ref name="PMID22496813"><pubmed>22496813</pubmed></ref> studied c-Jun N-terminal Kinase (JNK) activation in the retina of newborn rats

[[File:JNK1.png]]

<pubmed>20544023</pubmed>

<pubmed>20459797</pubmed>

[http://www.advancedcell.com/patients/clinical-trial-information/ Advanced Cell Technology]- A biotechnology company which is currently running two clinical trials that utilise human embryonic stem cell derived retinal pigmented epithelial cells. These trials are examining the possibility of using these cells to treat stargardt's macular dystrophy and dry age-related macular degeneration<ref><pubmed>22281388</pubmed></ref>.

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===LRP5 is required for vascular development in deeper layers of the retina===

<pubmed>20652025</pubmed>

{| width=800px
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|
The lipoprotein receptor-related protein 5 (LRP5) has a significant function in the development of retinal vasculature.<ref name="PMID20652025"><pubmed>20652025</pubmed></ref> Research has shown that mutations of the LRP5 causes loss of function, due to incomplete development of retinal vessel network, in both humans and mice. The authors investigated how mutations occur in the LRP5, which leads to abnormal development of the retinal vasculature. They have studied retinal endothelial cells in mutant mice in their study. Their results showed that in retina with mutated LRP5, endothelial cells in the retinal vasculature primarily produced cell clusters in the inner-plexiform layer instead of migrating into deeper layers of the retina to form normal retinal vasculature. The authors also discovered that there was a decrease in Slc38a5, which is a “a Müller cell-specific glutamine transporter”, in mice with mutated LRP5. Their results lead the authors to conclude that normal LRP5 is very important in the development of normal retinal vasculature due to their role in causing migration of retinal endothelial cells in the deeper layers of the retina. LRP5 is also important for retinal interneurons and Müller cells to function correctly.

|
[[File:Retina-cell-clusters.JPG|350px|thumbnail|'''Endothelial cells form thick clusters in the LRP5 mutant retina''']]
|}

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==Useful Links==

{{External Links}}

[http://www.youtube.com/watch?v=Xme8PA6xv-M Visualisation of eye development in the embryo]

[http://www.embryo.chronolab.com/sense.htm Embryonic Development of the eye]

==Glossary==

'''Accommodation''' - changing the focal length of the lens in order to focus on an object.

'''Downstream genes''' - genes that are activated by other "upstream genes".

'''Ectoderm''' - outermost layer of germ cells in an early embryo.

'''Endoderm''' - innermost layer of germ cells in an early embryo.

'''Glial cells''' - non-neuronal cells that provide structure and protection to neurons as well as producing myelin.

'''Inductive signaling''' - a process whereby the secretion of factors from one cell or tissue triggers a response in another.

'''Lens vesicle''' - the cavity of invaginated ectoderm from the optic placode that will form the lens.

'''Macula''' - a highly pigmented, oval-shaped area located near the centre of the retina. Important for visual acuity.

'''Mesenchyme''' - undifferentiated, loose connective tissue.

'''Mesoderm''' - middle layer of germ cells in an early embryo.

'''Mesothelium''' - the epithelial layer of the mesoderm.

'''Myelinisation''' - development of a myelin sheath around a nerve fibre.

'''Neural crest''' - a portion of the ectoderm situated next to the neural tube.

'''Neural groove''' - a large invagination on the dorsal surface of the embryo which will close off and form the neural tube.

'''Neural tube''' - hollow structure that results from the folding of the neural plate and eventually forms the central nervous system.

'''Neuroblastic layer''' - a layer of immature cells that differentiate to form either glial cells or neurons. The retina has two of these (an inner and outer).

'''Neuroectoderm''' - portion of the ectoderm that develops to form the central and peripheral nervous systems.

'''Optic chiasm''' - the point at which the optic nerves meet and cross over.

'''Optic cup''' - the structure that is formed after the optic vesicle folds in upon itself. This will form the retina.

'''Optic globe''' - a term that refers to the optic cup, lens vesicle and surrounding mesenchyme collectively.

'''Optic placode''' - area of thickened ectoderm that gives rise to the lens of the eye.

'''Optic stalk''' - a long, narrow cavity that will produce the optic nerve.

'''Optic vesicle''' - a cavity that buds off from the neural tube and gives rise to the optic cup.

'''Upstream genes''' - genes that activate one or more other "downstream genes".

'''Vascularise''' - to invade with blood vessels.

==Image Gallery==
<gallery>
Image:Eye_diagram_bandw.jpg‎ | Basic structure of the human eye.
Image:Stage14 sem2b-limb.jpg | A Stage 14 embryo showing the location of an otic placode.
Image:Stage 13 image 060.jpg | A cross section showing the organisation of the developing brain, the optic vesicle and the lens (optic) placode.
Image:Formation of the optic vesicle 1.jpg | Early formation of the optic vesicle from the neural groove.
Image:Formation of the optic vesicle 2.jpg | The optic vesicle at a later stage, showing the optic stalk.
Image:Formation of the optic nerve and chiasm 1.jpg | A recognisable brain and eye structure in later development.
Image:Formation of the optic cup 1.jpg | Mechanism of optic cup formation.
Image:Formation of the optic cup 2.jpg | Layers of the optic cup in retina development.
Image:Formation of the retina 1.jpg | Cross-section of the primitive retina showing cell types and layers.
Image:Formation of the retina 2.jpg | Cross-section of a developed retina showing cell types and layers.
Image:Formation of the lens 1.jpg | The importance of the optic cup in lens differentiation.
Image:Formation of the lens 2.jpg | The lens placode separates from the ectoderm and migrates into the mesoderm forming the lens vesicle.
Image:Formation of the choroid and sclera 1.jpg | The choroid and sclera derives from mesenchyme surrounding the optic cup.
Image:Formation of the eyelid 1.jpg | Small grooves in the ectoderm of the head - the precursors to an eyelid.
Image:Formation of the eyelid 2.jpg | The eye at an advanced stage of embryonic development. Note however, that the eyelids remain fused until much later.

</gallery>

==References==
<references/>

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--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

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{{2012Projects}}

2012 Group Project 1

2012-10-02T13:14:52Z

Z3254758: /* Iris */

[[File:Eye_collage_2.jpg|right|830px]]

=Vision Development=

==Introduction==

Eyes are an important sensory organ shared across many different species and allow organisms to gather useful visual information from their environment. The visual system uses light from the environment and processes this information in the brain for visual perception. The visual system is complex, and is made up of various structures that work together to form vision. Each of the structures in the eye have specific tasks which contribute to the visual system. Knowledge of how the eye develops extends as far back as Aristotle more than 2000 years ago, and current knowledge shows that most of the crucial events of eye development occur in the embryological stage. The eye is an interesting model for studying the development of tissues in organisms, as it consists of cells from several parts of the embryo including the head ectoderm, neural ectoderm and mesoderm. From its many origins the cells come together and differentiate to produce the complex organ that is the eye. During this period there are many examples of inductive signaling, as the tissues coordinate their development throughout this elegant process.

The main anatomical structures of the eye are as follows:
{|
|
* Cornea

* Sclera

* Choroid

* Iris

* Ciliary body

* Lens

* Anterior chamber

* Posterior chamber

* Retina

* Optic nerve

|[[File:eye_diagram_bandw.jpg|right|250px|thumb|Basic structure of the human eye.]]
|}
[[File:Eyediagramcolour1.JPG|550px]]

==Research History==

=== '''Brief Timeline of Historical Developments on the Eye and its Embryology''' ===

{| width=800px
|-bgcolor="CEDFF2"
| width=100px|'''Time'''
| width=700px|'''Discovery'''

|-bgcolor="F5FAFF"
| '''Ancient Egyptians'''
| First to document cataracts. It is described as being 'the white disease of the eye' or 'darkening of the pupil.' <ref>Edwards, D.D. (1996). Ophthalmology before Hippocrates. In the History of Ophthalmology, ed. D.M. Albert and D.D. Edwards. Cambridge, Mass.: Blackwell Science.</ref> The Egyptians had some knowledge of the eye, however it is not known how much of the anatomy of the eye was known in their era.

|-bgcolor="CEDFF2"
| '''535 BC'''

|
Ancient Greek philosopher Alcmaeon conducted dissection of humans for the first time in recorded history. This included dissection of the eye. However, not much is known about which anatomical features he discovered. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17.">Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17.</ref>

|-bgcolor="F5FAFF"
| '''384- 322 BC'''

| [[File:Aristotle-eye.jpg|200px|thumbnail|The eye according to Aristotle.<ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "> Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau </ref> Note the lens is missing, and there are three vessels drawn that was believed to transport fluid to and from the eye.<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
]]
Aristotle performed dissections of animal embryos.<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

When Aristotle described the embryo of a ten day old chicken, he wrote "The eyes about this time, if taken out, are larger than beans and black; if their skin is removed the fluid inside is white and cold, shining brightly in the light, but nothing solid." <ref name="Magnus, H. (1998). Ophthalmology of the ancients. In J. Hirschberg (Ed.), The History of Ophthalmology: The monographs, Vol. 4, Part 1 (F.C. Blodi, Trans.) Bonn: Wayenborgh.">Magnus, H. (1998). Ophthalmology of the ancients. In J. Hirschberg (Ed.), The History of Ophthalmology: The monographs, Vol. 4, Part 1 (F.C. Blodi, Trans.) Bonn: Wayenborgh.</ref>

Aristotle believed that the eyes started forming during early embryogenesis, however, he also believed that the eyes are the last organs to form completely, and he incorrectly thought that the eyes shrink in later embryonic development. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press.">Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press.</ref> .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"

| '''340 BC'''

| Lens is thought to have been discovered by Hippocrates, due to his descriptions of the contents of the internal eye There has been studies in chick development later on by followers of Hippocrates. They claimed that eyes were visible in early embryogenesis. .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
|-bgcolor="F5FAFF"
|'''25 BC - 50 AD'''

| [[File:Celsus-eye.jpg|150px|thumb|The eye according to Celsus. <ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "/>
Note the lens is placed in the centre of the eye, in the vitreous.<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> ]]

Aulus Cornelius Celsus wrote a Roman medical text called 'De Medicina' in which he wrote that the lens was the part of the eye from which vision originated. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.">Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.</ref> Celsus also incorrectly drew the lens in the center of the globe in his diagram of the eye. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

|-bgcolor="CEDFF2"
| '''23-79 AD '''
|
Pliny the Elder said that the eye is the last of the organs to develop in the womb <ref name="Magnus, H. (1998). Ophthalmology of the ancients. In J. Hirschberg (Ed.), The History of Ophthalmology: The monographs, Vol. 4, Part 1 (F.C. Blodi, Trans.) Bonn: Wayenborgh."/>
|-bgcolor="F5FAFF"
| '''98-117 AD'''

| [[File:Rufus-eye.jpg|150px|thumb|The eye according to Rufus of Ephesus. <ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "/>
Note the lens is placed in the correct position, behind the iris of the eye <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> ]]

Rufus of Ephesus identified the lens as being located in the anterior part of the eye, close to the pupil. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

His diagram illustrates that he knew the correct position of the lens as being directly behind the iris, in the anterior part of the eye, and not in the centre as was previously depicted by others before him.

|-bgcolor="CEDFF2"
| '''130-200 AD'''

| [[File:Galen-eye1.jpg|150px|thumb|The eye according to Galen. <ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "/> ]]

Claudius Galen practised medicine in Rome. He wrote:

"1. Within the eye the principal orgran of sensation is the crystalline lens.

2. The sensation potential comes from the brain and is conducted via the optic nerves.

3. All other parts of the eyeball are supporting structures." <ref> Hirschberge, J. (1982). Antiquity, Vol. X in the History of Ophthalmology (F.C. Blodi, Trans.) Bonn: Wayenborgh. pp. 280 </ref>

Galen thought that the lens was produced from the vitreous. He also believed that the retina’s function was to give nourishment to the lens and vitreous, and to carry visual information to the brain from the lens. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

|-bgcolor="F5FAFF"

| '''1514-1564'''

| Andreas Vesalius published his anatomy book "De Humani Corporis Fabrica in 1543. He had the misconception that the lens was located in the centre of the eyeball. .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> He also wrote that the lens functioned "like a convex lens made of glass" <ref name="Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.">Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.</ref> pp. 48
|-bgcolor="CEDFF2"
| '''1535-1606'''

| Georg Bartisch correctly drew a diagram of the lens placed behind the iris in his book 'Ophthalmodouleia: das ist Augendienst'. <ref name="Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>
|-bgcolor="F5FAFF"

| '''1537-1619'''

| Fallopio Hieronymus Fabricius ab Aquapendente studied anatomy and embryology. He studied chicken embryos, and thought that chalazae (which comes from egg white) gives rise to the eyes. He also drew the lens directly behind the iris in a diagram in is book 'Tractatus de Oculo Visuque Organo. <ref name="Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

|-bgcolor="CEDFF2"
| '''1583'''

| Felix Platter published his book 'De corporis Humani Structura et Usu, after he performed dissections of human bodies. He believed that the retina is the primary visual organ in the eye. .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="F5FAFF"
| '''1619'''
| Scheiner is given credit to be the first person to correctly draw the diagram of the anatomy of the eye. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
|-bgcolor="CEDFF2"
| '''1672'''
| Marcello Malpighi described the embryonic development of the chicken. He drew many detailed diagrams of the chick eye. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1665'''
| Nicolaus Steno identified the choroid fissure in his study of a developing embryo of a chicken. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="CEDFF2"
| '''1754'''

| Albrecht von Haller studied the embryology of the eye. With help from his student Johann Gottfried Zinn, he contributed to the understanding of the development of the ciliary body, ciliary zonule, and their relationship with the lens and vitreous. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1817'''

| Christian Pander discovered the three embryonic germ layers, which he wrote about in his book. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/> Pander was the first to think of 'the optic vesicles as lateral evaginations' of the 'prosencephalon'; however, he was incorrect about the details regarding how 'the eye develops from these evaginations'. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="CEDFF2"
| '''1828-1837'''

| Karl Ernst von Baer studied embryology. He discovered that the optic vesicles were 'outgrowths of the embryonic forebrain' <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> which he believed was caused by pressure from fluids in the central nervous system. Von Baer also believed that the optic vesicle opens to form the pupil, and that fluid in the optic vesicle coagulates to form the vitreous body and lens. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1830'''

| Emil Huschke discovered that the lens forms from the invagination of the surface ectoderm. He concluded that the lens hence does not form ‘from the fluid of the optic vesicle’ <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> as previously thought.
|-bgcolor="CEDFF2"
| '''1832'''

| Emil Huschke wrote in his manuscript ‘Ueber die erste Entwinkenlung des Auges und die damit zusammenhängende Cyklopie’ that the lens capsule forms from the outer surface ectoderm, which detaches and moves back inward, which is later enclosed again by several membranes, such as by the cornea. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

Huschke also described how the optic cup and choroid fissure forms. He discovered that the optic vesicles are produced from the two-layered optic cup. However, he incorrectly described the destiny of the ‘individual optic cup layers’. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

|-bgcolor="F5FAFF"
| '''1838'''
| Matthias Jakob Schleiden and Theodor Schwann formulated the ‘cell theory’: “All living things are formed from cells, the cell is the smallest unit of life, and cells arise from pre-existing cells.” <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
|-bgcolor="CEDFF2"
| '''1839'''

| Theodor Schwann contributed a better understanding of the development of the lens through studying the foetus of a pig, which he wrote about in his book ‘Mikroskopische Untersuchungen Über Die Uebereinstimmung in Der Struktur Und Dem Wachsthum Der Thiere Und Pflanzen’. He wrote that the lens is made of ‘concentric layers’ of fibres which proceeds from an anterior to posterior direction. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1842'''
| Robert Remak gave the current names to the three embryonic germ layers: ectoderm, mesoderm and endoderm. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"
| '''1843'''
| Wilhelm Werneck published his book ‘Beiträge zur Gewebelehre des Kristallkörpers’. He wrote that the contents inside of the lens is not made of fluids, as was previously believed. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/> Werneck also discovered that the fibers of the lens continues to grow from the outside to the centre during embryogenesis. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

|-bgcolor="F5FAFF"
| '''1855'''

| Robert Remak wrote his book ‘Untersuchungen über die Entwickelung der Wirbelthiere’. He wrote about what he discovered in his studies of the development of the eye in the embryos of chickens, frogs, and rabbits. He wrote very descriptively about the embryology of lens formation, amongst other topics. He discovered that the ectoderm gives rise to the lens placode. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

|-bgcolor="CEDFF2"
| '''1858'''
| Henry Gray published his book 'Anatomy, Descriptive and Surgical'. He had also previously studied the embryonic development of the optic nerve and retina of chickens.
|-bgcolor="F5FAFF"
| '''1877'''
| Paul Leonhard Kessler wrote about the embryonic development of the lens in mice in his book ‘Zur Entwickelung des Auges der Wirbelthiere. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"
| '''1891'''
| Vincenzo Colucci studied newts and discovered their ability to regenerate the lens.<ref> Tsonis, P. A. (2001). Regeneration of the Vertebrate Lens and Other Eye Structures. eLS. (Online Publication). DOI: 10.1038/npg.els.0001102 </ref>
|-bgcolor="F5FAFF"
| '''1892'''
| Dr. Oscar Hertwig published his book ‘Text-Book of the Embryology of Man and Mammals. <ref> Hertwig, O. Text-book of the embryology of man and mammals. S. Sonnenschein 1901. (Translated from the 3d German ed. by Edward L. Mark.) </ref> It contains a very detailed description of the development of the eye, according to the findings at that time. [http://embryology.med.unsw.edu.au/embryology/index.php?title=Book_-_Text-Book_of_the_Embryology_of_Man_and_Mammals_16-2#The_Development_of_the_Eye]
|-bgcolor="CEDFF2"
| '''1895'''
| Gustav Wolff also independently studied newts and discovered their ability to regenerate the lens. .<ref> Tsonis, P. A. (2001). Regeneration of the Vertebrate Lens and Other Eye Structures. eLS. (Online Publication). DOI: 10.1038/npg.els.0001102 </ref>

|-bgcolor="F5FAFF"

| '''1900'''
| Carl Rabl published his book ‘Uber den Bau und die Entwicklung der Linse’. He wrote about the development of the lens in mammals, fish, birds, reptiles, and amphibians. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="CEDFF2"
| '''1901'''
| Hans Spemann published his findings from his experimental studies about the formation of the lens in the frog. He found that the optic cup needed to be in contact with the ectoderm for normal development of the eye. <ref> Spemann, H. (1901). Über Correlationen in der Entwicklung des Auges. Verhand. Anat. Ges. 15: 61-79. </ref> <ref> Saha, M. (1991). Spemann seen through a lens. In Gilbert, S. F. (ed.). A Conceptual History of Modern Embryology. Plenum Press, NY. pp. 91-108.</ref>
|-bgcolor="F5FAFF"
| '''1906'''
| Brown ‘s book “The Embryology Anatomy and Histology of the Eye” was published. It contained detailed descriptions of the embryonic development of the eye according to the knowledge current at that time, mainly based on observations from embryos of rabbits and chickens. <ref> Brown, E.J. (1906). The Embryology Anatomy and Histology of the Eye. Chicago: Hazlitt & Walker. 1906 </ref>

|-bgcolor="CEDFF2"
| '''1907'''

| John Clement Heisler published his book ‘A Text-book of embryology’. It contains a chapter detailing the embryonic development of the eye, according to the knowledge current at that time. The book’s copyright has expired, so it can be viewed free online: [http://archive.org/details/atextbookembryo01heisgoog]

Julius Kollman also published his book 'Atlas of the Development of Man'. It contained very detailed description and illustrations showing the embryonic development of the human according to the knowledge current at that time. His illustrations were reused by many others after his time and built upon for further refined understanding of the embryology of the human.

Here are examples of Julius Kollman's excellent illustrations showing eye development in various stages:

'''Formation of Primary Optic Vesicle:'''
<gallery>
File:Kollmann691.jpg|The blue part at the bottom is the endoderm. The pink middle layer is the mesoderm. The top yellow layer is the ectoderm. The fold labelled as 'augenfeld' is the place where the optic vesicle will form.
File:Kollmann692.jpg|The eye area (augenfeld) is a bowl shaped bulge still located on the side walls.
File:Kollmann693.jpg| The neural tube is shown after removal of all of the ectoderm and ventral organs, such as heart, gut tube, etc. The primary optic vesicle forms a slightly flattened hollow protrusion on the forebrain.
File:Kollmann694.jpg|The lateral surface of the primary optic vesicle is slightly depressed, showing the first sign of the emergence of the secondary optic vesicle
</gallery>

'''Development of Lens:'''

<gallery>
File:Kollmann695.jpg|The bulging lateral wall of the primary optic vesicle is covered by a fairly well demarcated lens plate, a direct continuation of the ectoderm. Between the optic vesicle and the lens pit are some flattened spindle-shaped cells. In the adjoining mesoderm are cross-sections of capillaries.
File:Kollmann697.jpg|The lens still hangs together with the ectoderm. The primary eye vesicle is indented with respect to the lens. Between the lens and the lateral plate of the optic vesicle is a narrow space, which allows area to further develop later.
File:Kollmann698.jpg|4th Week of development. The internal organisation shows the secondary optic vesicle. A: The rear wall of lens is noticeable and is enveloped by mesoderm. B: The edges of the lens pit is already grown and the lens vesicles are formed, which is still related to the remaining ectoderm.
File:Kollmann699.jpg|The lens has now cut off from the ectoderm, but is still very superficial. Between it and the lateral lamina of the optic cup, there is a considerable space. The eye stalk has become longer and is enclosed together with the optic cup and lens of the mesoderm. The cornea, sclera and choroid make gradual development.
</gallery>

|-bgcolor="F5FAFF"

| '''1921'''
| Bailey and Miller published their textbook “Text-Book of Embryology “. <ref> Bailey, F.R. and Miller, A.M. (1921). Text-Book of Embryology. New York: William Wood and Co. (Note- This book is only at an early edited stage)</ref> It contains detailed description of the development of the embryonic eye according to the knowledge current at that time. [http://embryology.med.unsw.edu.au/embryology/index.php?title=Book_-_Text-Book_of_Embryology_18]

|-bgcolor="CEDFF2"
| '''1925'''

| Mann published his research article, in which he gives a detailed account of the development of the human iris. He divided the development of the iris into four stages: weeks 4-7 (before the ectodermal iris forms or before the anterior chamber forms); weeks 7-11 (anterior chamber appears, and mesodermal iris forms); weeks 11-12 (ectodermal iris forms); 3-8 months (muscles of the pupil forms from ectodermal iris, and the central portion of the mesodermal iris atrophies to make the pupil clear). <ref name="PMID18168466"><pubmed>18168466</pubmed></ref>
O Leser also published an article detailing the development of extraocular muscles in mammals he studied. <ref name="PMID18168498"><pubmed>18168498</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1939'''
| Holtfreter <ref> Holtfreter, J. (1939). Gewebeaffinitat, ein Mittel der embryonalen
Formbildung. Arch. Exp. Zellforsch. 23, 169-209. </ref> studied amphibians and observed that that the development of the eye stops at the ‘optic vesicle stage’ if there is no contact ‘with the epidermis and neural crest driven mesenchyme’. <ref name=”PMID11023863”><pubmed>11023863</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1955'''
| Barber published his book ‘Embryology of the human eye’. <ref> Barber AN: Embryology of the human eye. St. Louis. CV Mosby 1955</ref> In contains detailed descriptions of the embryological development of the human eye according to the knowledge current at that time. It contains many photographs of the eye at different stages of development.

|-bgcolor="F5FAFF"
| '''1957'''
| Coulombre studied a chicken embryo to find the role of intraocular pressure in the development of the chick’s eye, especially in regards to its control of the size of the eye structures. <ref name="PMID13469954"><pubmed>13469954</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1958'''
| Coulombre studied the development of the cornea and how it develops its transparency. <ref name="PMID13563560"><pubmed>13563560</pubmed></ref> He also studied the development of corneal curvature. <ref name="PMID 13519969"><pubmed> 13519969</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1962'''
| Coulombre studied the development of the conjunctival papillae and scleral ossicles. <ref name="PMID 14023393"><pubmed> 14023393</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1963'''
| Coulombre studied the development of lens fibers and their orientation. <ref name="PMID14077035"><pubmed>14077035</pubmed></ref> He also studied the development of pigmented epithelium. <ref name="PMID14023394"><pubmed>14023394</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1964'''

| Coulombre further studied the development of the lens to determine the role of the lens in eye growth. <ref name="PMID14189921"><pubmed>14189921</pubmed></ref> He also studied the role of thyroid in the development of the cornea and the development of corneal transparency. <ref name="PMID14211912"><pubmed>14211912</pubmed></ref> Mann also published his work called ‘The development of the human eye’, which contains detailed description of the embryonic development of the eye according to current knowledge at that time. <ref> Mann I. The development of the human eye. New York: Grune and Stratton 1964</ref>

|-bgcolor="CEDFF2"
| '''1965'''
| Coulombre published his findings regarding the regeneration of the neural retina from pigmented epithelium in the embryo of chickens. <ref name="PMID5833111"><pubmed>5833111</pubmed></ref> Smelser also published his findings on the embryological development and morphology of the lens. <ref name="PMID14340157"><pubmed>14340157</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1966'''

| Formation of the face and orbit occurs from the differentiation of neural crest cells. <ref name="PMID5969670"><pubmed>5969670</pubmed></ref> O’Rahilly also published findings of the development of the eye in the early stages of human embryos. <ref> O'Rahilly, R. 1966 The early development of the eye in staged human embryos. Contr. Embry. Carnegie Inst., Wash., 38: 1–42</ref>

|-bgcolor="CEDFF2"
| '''1968'''
| Findings of the postnatal development of the retina of rats was published. <ref name="PMID5640327"><pubmed>5640327</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1969'''

| Mann again published his work called ‘The development of the human eye’. He stated that that the lens in humans forms completely from the ectoderm. <ref name=”Mann I. The Development of the Human Eye. New York, USA: Grune & Stratton, Inc; 1969”> Mann I. The Development of the Human Eye. New York, USA: Grune & Stratton, Inc; 1969</ref> Coulombre also studied the development of the lens, and took note of its size, shape and orientation throughout its developmental stages. <ref name="PMID 5772716"><pubmed> 5772716</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1970'''
| Coulombre again further studied the regeneration of the neural retina from pigmented epithelium of embryos of chickens. <ref name="PMID 5472476"><pubmed> 5472476</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1971'''

| Coulombre further studied the development of the lens. This time he focused on analysing the histological mechanisms in the reconstitution of the lens from implanted lens epithelium. <ref name="PMID 4925671"><pubmed> 4925671</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1973'''
| A research article was published, detailing the embryonic development of the retina of humans. <ref name="PMID 6650859"><pubmed> 6650859</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1976'''

| Geeraets published his observations of the closure of the embryonic optic fissure in golden hamsters, using the electron microscope. <ref name="PMID 1266776"><pubmed> 1266776</pubmed></ref> Kornneef also published an article based on his studies of the development of connective tissue in the human orbit. <ref name="PMID 1020699"><pubmed> 1020699</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1981'''
| A research article was published detailing how myelin forms in the optic nerve of humans. <ref name="PMID 7224936"><pubmed> 7224936</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1983'''
| O’Rahilly’s further research developments was published, reporting the timing and sequence of events in the development of the embryonic human eye. <ref name="PMID 6650859"><pubmed> 6650859</pubmed></ref>

|-bgcolor="CEDFF2"
| '''1990'''

| Van Driell et al. <ref>Driell, D. Van; Provis, J.M.; Billson, F.A.: Early differentiation of ganglion, amacrine, bipolar and Muller cells in the developing fovea of the human retina. J. Comp. Neurol. 291: 203-219.</ref> studied the manner in which amacrine, bipolar, retinal ganglion cells, and Muller cells differentiate in the developing fovea of the retina of a 15-week old human foetus. <ref name="PMID1628748"><pubmed>1628748</pubmed></ref> Tripathy also published an article providing evidence that the lacrimal glands in humans originates from the neuroectoderm. <ref name="PMID2406219"><pubmed>2406219</pubmed></ref>

|}

==Development, Structure and Function of Ocular Components==

The eye itself is formed from several components; notably the optic placode of the head ectoderm, the optic vesicle from the neural tube, and mesenchyme from the mesoderm and neural crest cells. The optic placode contributes the lens to the eye, the optic vesicle gives rise to layers of the retina, while the mesenchyme will produce the ciliary body, iris, choroid and sclera.<ref>http://www.vetmed.vt.edu/education/curriculum/vm8054/eye/EMBYEYE.HTM</ref> Cells from the neural tube will also produce the optic nerve, which receives nerve impulses from the retina of the eye. Eyes initially form as laterally paired structures and migrate medially in the human embryo. In other animals such as birds and lizards, the eyes do not migrate and develop laterally on the head. The optic placodes become prominent on the surface of the embryo at approximately Stage 14 of development.

[[File:Stage14 sem2b-limb.jpg|200px|thumb|left|A Stage 14 embryo showing the location of an otic placode.<ref name="http://embryology.med.unsw.edu.au/embryology/index.php?title=ANAT2341_Lab_6_-_Early_Embryo">http://embryology.med.unsw.edu.au/embryology/index.php?title=ANAT2341_Lab_6_-_Early_Embryo</ref>]] [[File:Stage 13 image 060.jpg|400px|thumb|center|A cross section showing the organisation of the developing brain, the optic vesicle and the lens (optic) placode.<ref name="http://embryology.med.unsw.edu.au/embryology/index.php?title=ANAT2341_Lab_6_-_Early_Embryo"/>]]

===Optic Nerve===

The optic nerve consists of nerve fibres that transmit information from the retinal photoreceptor cells to the brain. The optic nerve is formed from the optic stalk, which develops as the optic vesicle migrates from its origin in the neural tube to its destination - the surface ectoderm - where it will fuse with the optic placode (also known as the lens placode, which will contribute the lens to the eye).<ref name="PMID11687490"><pubmed>11687490</pubmed></ref>

[[File:Formation of the optic vesicle 1.jpg|400px|thumb|left|Fig. 1: Early formation of the optic vesicle from the neural groove.]] [[File:Formation of the optic vesicle 2.jpg|400px|thumb|center|Fig. 2: The optic vesicle at a later stage, showing the optic stalk.]]

As can be seen in Figure 1 above, the optic vesicle forms from the neural tube. However, note that the neural tube has not yet closed, and is still the neural groove at this point. Figure 2 then shows the optic vesicle at slightly later stage in the same simplified cross-section of the embryo, as it migrates from the neural tube to the surface ectoderm. Note the presence of the optic stalk which links the optic vesicle to the neural tube. Later in development, this primitive structure will become the optic nerve, which will link the eye to the brain.

The nerve fibres themselves will initially originate from the retinal ganglion cells in the eye during week 6.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008">Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008</ref> After two weeks, these fibers will have grown along the inner wall of the optic stalk and have reached the brain. They grow both in length and width, with the nerve fibres filling the hollow optic stalk to form the solid optic nerve. More than one million nerve fibers will eventually make up the optic nerve, along with glial cells which arise from the inner wall of the optic stalk itself.<ref><pubmed>1451666</pubmed></ref> Myelinisation of the optic nerve begins much later in development at around 7 months, beginning at the optic chiasm and moving towards the eye.<ref><pubmed>7224936</pubmed></ref> The optic chiasm forms just before the nerves reach the brain, and is where half the nerve fibres from each eye will cross over to the opposite side of the brain. This is demonstrated in Figure 3. Note the crossing over of the optic nerves just before they enter the brain, at the optic chiasm. This organisation is now much more familiar, with the eyes near the ectoderm and the optic nerve leading through the mesoderm to the brain buried deep in the embryo.

[[File:Formation of the optic nerve and chiasm 1.jpg|400px|thumb|center|Fig. 3: A recognisable brain and eye structure in later development.]]

===Retina===

The retinal component of the eye is formed when the optic vesicle folds in upon itself, forming the optic cup (see Figure 4). In doing so it creates two layers - an inner wall and an outer wall of the optic cup (Figure 5). These two layers of the optic cup will give rise to the two layers of the retina - the inner neural retina, and the outer pigmented epithelium.<ref name="PMID11687490"/> Note the existence of the space between the two layers of the retina. This is known as the intraretinal space and disappears by the 7th week of development, however the two layers never completely fuse and can become separated as a result of physical trauma to the head - leading to a detached retina and loss of vision.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/>

The inner wall of the optic cup, which will give rise to the neural retina, consists of a layer of pseudostratified cells (see Figure 6) that later differentiate into rod, cone, bipolar, ganglion, horizontal, amacrine and glial cells of the retina (Figure 7).<ref name="PMID18168748"><pubmed>18168748</pubmed></ref> The outer wall of the optic cup consists of a layer of cuboidal cells that contain melanin - the light absorbing pigment. The function of this layer is to absorb light and prevent internal reflection of light within the eye, which would impair our ability to form distinct images. Interestingly, in some animals such as cats, this layer actually reflects light intentionally to increase the amount of light available to the eye in low-light conditions. This is why cats seem to have eyes that glow in the dark.<ref>http://dialspace.dial.pipex.com/agarman/bco/fact4.htm</ref>

[[File:Formation of the optic cup 1.jpg|400px|thumb|left|Fig. 4: Mechanism of optic cup formation.]] [[File:Formation of the optic cup 2.jpg|400px|thumb|center|Fig. 5: Layers of the optic cup in retina development.]]

The inner wall itself is divided into two components - the inner neuroblastic layer and the outer neuroblastic layer (see Figure 6). The outer neuroblastic layer forms the rod and cone cells while the inner neuroblastic layer forms the remaining cell types found in the retina - the bipolar, ganglion, horizontal, amacrine and glial cells (Figure 7).<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/> The organisation of the retina is interesting in that incoming light passes through several layers of these neural retina cells before it is detected by rod and cone cells at the back of the retina, and then nerve signals are passed back through the layers of neural retina cells that the light just passed through moments before - a seemingly strange design that the eye does not share with man-made light-capturing devices such as a camera (imagine putting the wires in front of the image sensor!).

Differentiation of the neuroblastic layers into neural retina cells occurs in a pattern both within the layers and across the retina. Cells differentiate from the inner neuroblastic layer to the outer neuroblastic layer, and differentiate from the central retina to the peripheral retina.<ref name="PMID18168748"/> The macula is first identifiable in week 22 when ganglion cells start to form multiple rows, and the primitive fovea begins to form at approximately the same time as a depression in the macula.<ref><pubmed>6462623</pubmed></ref> It is not until 15-45 months after birth that this area becomes exclusively populated by cone cells and becomes the fovea centralis - the area of the retina with the highest visual acuity.

[[File:Formation of the retina 1.jpg|400px|thumb|left|Fig. 6: Cross-section of the primitive retina showing cell types and layers.]] [[File:Formation of the retina 2.jpg|400px|thumb|center|Fig. 7:Cross-section of a developed retina showing cell types and layers.]]

===Ciliary Body===

The ciliary body consists of ciliary processes and three portions of fibres that constitute the ciliary muscles. It functions to maintain normal eye physiology as well as playing a direct role in accommodation.

During development, the ciliary processes form slightly posterior to the iris, developing from part of the anterior rim of the optic cup. It is thought that the folded structure of the ciliary processes is brought about by intraocular pressure and specific signalling pathways.<ref name="PMID16959249"><pubmed>16959249</pubmed></ref> While the ciliary muscles and the endothelial cells of the ciliary blood vessels are chiefly formed by mesenchymal cells<ref><pubmed>16249499</pubmed></ref>, the neural crest and neuroectoderm also contribute to their development.<ref><pubmed>12127103</pubmed></ref> The normal development of the ciliary body is dependent on the correct expression of bone morphogenetic protein (BMP)-4, which is a member of the transforming growth factor-β superfamily.<ref><pubmed>1222340</pubmed></ref> Napier and Kidson (2007) summarised numerous genes that have been associated with ciliary body development, however their direct roles have not been well documented.<ref name="PMID16959249"/>

===Iris===

The iris is a thin layer that develops at the end of the third month of development and is derived from the anterior rim of the optic cup. The stroma of the iris develops from cells of neural crest cell origin.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/> The muscles that are responsible for the dilation and constriction of the pupil (dilator pupillae and sphincter pupillae muscles) form from the neuroectoderm of the optic cup. These cells are initially epithelial cells that then transform into smooth muscle cells. <ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"></ref>. The invagination of the optic vesicle which creates the optic cup, also causes the formation of the optic cup lip. This is the region of the where the epithelium doubles back, separating the outer pigmented layer and the inner nonpigmented layer. This is the edge of the iris that borders on the pupil<ref><pubmed> Retinal and anterior eye compartments derive from a common progenitor pool in the avian optic cup</pubmed></ref>.
The final colour of the iris is not evident until the postnatal period. It is determined by a number of genes including IRF4, SLC24A4 and MATP<ref><pubmed>19710684</pubmed></ref>. Other features such as crypt frequency, furrow contractions, presence of peripupillary pigmented ring, and number of nevi also become evident during development<ref><pubmed>21835309</pubmed></ref>.
Mutations in Pax6 have been shown to cause partial or complete loss of the iris <ref><pubmed>12386935</pubmed></ref>.

===Lens===

The lens has its origin from the optic placode, which develops on the ectodermic surface of the embryo and migrates both medially and inwards into the embryo. The lens allows accommodation of the eye, and adjusts its thickness in order to focus on near or far objects. The study of lens development was one of the first to highlight the importance of inductive signaling in development, with Spemann's pioneering work at the start of the 20th century, finding that the absence of retinal development resulted in the absence of lens formation.<ref name="PMID11687490"/> Indeed, it has been consistently shown that the interaction of the migrating optic vesicle with the surface ectoderm of the head is vital in producing differentiation of the lens.<ref name="PMID15558475"><pubmed>15558475</pubmed></ref> The mechanism of interaction is complex but basically involves upstream genes switching on downstream genes, with the genes eventually producing specialised proteins which constitute the lens. The whole process starts with the signaling molecules from the optic cup initiating a thickening of the surface ectoderm of the head (Figure 8). It is thought that this region of specific ectoderm is responsive to the signaling molecules, as lens formation is incomplete or absent when ectoderm from the lateral portion of the embryo (i.e. non-head ectoderm) is exposed to the same inductive signaling processes.<ref name="PMID9216064"><pubmed>9216064</pubmed></ref> Pax6 has been shown to be one of the major genes required for differentiation of the lens, which in turn switches on transcriptional genes such as Sox 1, 2 and 3 among others - producing water-soluble proteins called crystallins - responsible for giving the lens its transparency and refractive properties.<ref name="PMID9609835"><pubmed>9609835</pubmed></ref>

[[File:Formation of the lens 1.jpg|400px|thumb|left|Fig. 8: The importance of the optic cup in lens differentiation.]] [[File:Formation of the lens 2.jpg|400px|thumb|center|Fig. 9: The lens placode separates from the ectoderm and migrates into the mesoderm forming the lens vesicle.]]

The lens placode invaginates from the head ectoderm and migrates into the mesoderm (Figure 9). Once this structure (now known as the lens vesicle) is in place opposite the optic cup, the combined structure is referred to as the optic globe and resembles a recognisable eye structure. The lens continues to differentiate further, as mentioned above, through the formation of crystallin proteins, which give the lens its unique properties and allows for the fine control over the degree of refraction that takes place.

===Aqueous Chambers===

There are both anterior and posterior aqueous chambers of the eye which contain aqueous humour. A space develops in the mesenchyme situated between the lens and cornea to form the anterior aqueous chamber. The mesenchyme located superficially to this chamber forms the mesothelium as well as the transparent portion of the cornea.

The posterior chamber develops from a similar space in the mesenchyme, however it is located between the iris and the lens. The anterior and posterior chambers are able to communicate with one another once the papillary membrane vanishes and the pupil is formed. This channel is known as the scleral venous sinus.<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011">Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011</ref>

===Cornea===

The cornea is the transparent, avascular, most anterior portion of the eye. It is responsible for conducting light into the eye and focusing it on to the retina, as well as maintaining the rigidity of the eyeball. It consists of 5 layers- the epithelium, Bowman’s layer, stroma, Descemet’s membrane and the endothelium.

The epithelium and endothelium of the cornea first appear during the 5th week of gestation. The epithelium of the external surface of the cornea is derived from surface ectoderm, while the mesenchyme is derived from the mesoderm<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"/>. The endothelium is a two-cell cuboidal layer which is made up of differentiated neural crest cells that were initially from the optic cup. By week 8 the endothelial cells begin to secrete a basement membrance which later forms Descemet’s membrane<ref><pubmed>6511224</pubmed></ref>. At approximately 16 weeks gestation the Bowman’s membrane begins to form from the thickening of the stroma that is located under the corneal epithelium<ref>Riordan-Eva P, Whitcher JP. Vaughn and Asbury's General Ophthalmology, Lange Medical Books/McGraw Hill. 2004:25–27</ref>. During the third month glycosaminoglycans secreted by fibroblasts form the ground substance of the cornea, with collagen fibrils and keratan sulphate also appearing around this time. Shortly after this tight junctions form between the endothelial cells<ref><pubmed>19481138</pubmed></ref>. Towards the end of the gestational period the cornea becomes larger due to the production of aqueous humor<ref>Yanoff M, Duker JS. Ophthalmology. Mosby; St. Louis, MO: 2004</ref>. The final transparent structure develops because hyaluronidase removes hyaluronic acid, thyroxine causes dehydration of the stroma, and the entire structure becomes avascular<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/>. Numerous genes have been implicated in the development of the cornea, these include, but are not limited to, PAX6, PITX2, FOXC1, MAF, TMEM114, SOX2, OTX2 and BMP4<ref><pubmed>18637741</pubmed></ref>.

===Choroid and Sclera===

The choroid and sclera are adjacent layers that surround the eye and act to vascularise and protect the eye respectively. They are formed from neural crest and mesoderm-derived mesenchyme which condenses around the optic cup and lens vesicle between weeks 5 and 7 of development to form a primitive eyeball structure known as the optic globe.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/> Blood vessels first start to appear in the choroid layer at approximately week 15, and arteries and veins can be distinguished by week 23.<ref>Development of the Choroid and Related Structures, K. Sellheyer, Eye (1990) 4, 255-261</ref> Inductive processes are thought to play a vital role during formation of the choroid and sclera; with the retinal pigmented epithelium inducing differentiation of the surrounding mesenchyme while at the same time the neural crest-derived mesenchyme contributing components to the retinal pigmented epithelium such as melanocytes.<ref name="PMID1628748"/> In addition to having functional roles themselves, the primitive choroid and sclera also contribute components to the developing ciliary body and cornea (Figure 10). In the adult eye, the choroid is continuous with the ciliary body and the sclera with the cornea.

[[File:Formation of the choroid and sclera 1.jpg|400px|thumb|center|Fig. 10: The choroid and sclera derives from mesenchyme surrounding the optic cup.]]

===Eyelids===

The eyelids are ectodermal and mesodermal in origin and are an extension of the skin which covers and protects the eye. Eyelid formation can be first noted during week 5 when small grooves develop in the surface ectoderm (Figure 11).<ref><pubmed>7364662</pubmed></ref> These small grooves deepen and extend into the mesoderm and the primitive eyelid structures grow towards one another, eventually fusing together during week 8.<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"/> It is not until week 26-28 that the eyelids will separate again. The ectoderm reflects over the developing cornea to form the conjunctival sac, a space that is filled by secretions from the lacrimal gland in order to allow smooth motions of the eyelid over the eye and also to clean the cornea and prevent accumulation of particles on the eye that may disrupt vision. By the time the eyelids separate, the eye has all its major components present (Figure 12), and further development consists mainly of growth and vascularisation.

[[File:Formation of the eyelid 1.jpg|400px|thumb|left|Fig.11: Small grooves in the ectoderm of the head - the precursors to an eyelid.]] [[File:Formation of the eyelid 2.jpg|400px|thumb|center|Fig. 12: The eye at an advanced stage of embryonic development. Note however, that the eyelids remain fused until much later.]]

===Lacrimal Glands===

Lacrimal glands initially develop from budding of the conjunctival epithelium near the superolateral portion of the eye. The mesenchymal cells that surround these buds are of neural crest origin, and the budding continues until the mature gland is formed.<ref><pubmed> 9882499</pubmed></ref> These glands are responsible for the production of tears however they do not start to function until 1-3 months after birth.

==Current Research==

*more info will be added soon!!

===GABA Maintains the Proliferation of Progenitors and Non-Pigmented Ciliary Epithelium===

<pubmed>22590629</pubmed>

{| width=800px
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|-
| GABA is an ‘inhibitory neurotransmitter’ in the central nervous system of adults. <ref name="PMID22590629"><pubmed>22590629</pubmed></ref> It is responsible for controlling proliferation of stem cells and progenitor cells. The authors of this article <ref name="PMID22590629"/> was interested to find the effects of GABA on proliferation of progenitor cells and non-pigmented ciliary epithelial cells (NPE) in the retina. Their study focused on progenitor cells and non-pigmented epithelium of the ciliary body in chickens. Non-pigmented epithelial cells in chickens arise from the neuroepithelium of the optic cup. They share similar functions as progenitors of the early retina, such as expression of Chx10 and Pax6 genes. It is not agreed upon whether epithelial cells of the ciliary body have stem cell properties. However, it has been found that these cells can be cultured and transplanted into retinas that are injured, in order to replace neurons that were previously lost. However, there is not much known about what factors regulate the proliferation of stem cells. Hence the authors were interested in finding the effects of GABA on proliferation of retinal cells. Their results showed that non-pigmented epithelial cells in chickens ‘express extrasynaptic-like GABAA receptors’ that have the ability to regulate cell proliferation. It has been found that inhibiting these ‘GABAA receptors’ also causes a decrease in proliferation of retinal progenitor cells and non-pigmented epithelial cells in 'the intact E8 retina’. <ref name="PMID22590629"/>

|
[[File:Gaba-effects-retina.JPG|thumbnail|250px|'''GABAA receptor mediated effects on retinal progenitor cell proliferation'''
]]
|}

-------------------

===The impact of visible light on the immature retina===

<pubmed>22405869</pubmed>

The authors mentioned in this article <ref name="PMID22405869"><pubmed>22405869</pubmed></ref> that they were interested in investigating the effect of light on postnatal eye development in mice, because mice are born with fused eyelids, which separate 12 days after birth. Before the eyelids separate, the retina develops in mice with very little radiation from light. It is believed that the darkness plays a role in the development of the retina in mice, which is why their eyelids are fused for 12 days after birth. Therefore the authors were interested to see what effect light would have on postnatal retinal development of mice, with special interest in retinal ganglion cells (RGC). In their experiment, they surgically opened the eyelids on the right eyes of some of the mice to expose them to visible light 12 hours per day, while they left some other mice in the dark after surgical separation of their eyelids. They also kept the left eyes of the mice naturally fused as controls in the experiment. Their results showed that early light exposure in mice causes a decrease in retinal ganglion cells because it affects cellular apoptosis in the retina. The authors also observed that early exposure to light in mice causes lumican mRna transcription to resume and to quickly increase. (Lumican normally stays silent in retina after birth).

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===MIP/Aquaporin 0 Represents a Direct Transcriptional Target of PITX3 in the Developing Lens===

<pubmed>21698120</pubmed>

{| width=800px
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|PITX3 plays a siginificant role in the development of lens in vertebrates. If there is a deficiency is PITX3, it causes a range of problems in humans such as microphthalmia, Peter’s anomaly, or isolated cataracts. Mutation of PITX3 also causes degeneration of the lens in zebrafish and mice. It is therefore important to understand what factors may affect the decrease in PITX3, as a normal level of PITX3 is needed to maintain normal eye development. The authors wanted to investigate specific genes which are affected by PITX3. Previous research has shown that MIP and Aquaporin causes defects in the lens in both mice and humans. MIP and Aquaporin are targeted by PITX3, so their imbalance is interrelated in the cause of defects in the lens. Therefore it has been previously proven that PITX3 is needed for normal development of the lens. However, there has not been much information previously known regarding the exact effect that PITX3 has, or the specific genes it targets. Since MIP and Aquaporin is common genes found in humans, mice and zebrafish, the authors <ref name="PMID21698120"><pubmed>21698120</pubmed></ref> chose to study these genes to understand the pathway that PITX3 takes and its exact involvement in the development of the lens. Their results proved that deficiency in MIP and Aquaporin indeed affects normal development of the lens, and it is indeed related to deficiency in PITX3. However, there is still more research needed to understand PITX3 and the genes it interacts with, and their effect in ocular development.

|
[[File:Mip1-expression-in-pitx3.jpg|thumbnail|250px|'''Analysis of mip1 expression in pitx3-mo and control embryos via in situ hybridization and RT-PCR''']]
|}

-----------

<pubmed>22496813</pubmed>

This research <ref name="PMID22496813"><pubmed>22496813</pubmed></ref> studied c-Jun N-terminal Kinase (JNK) activation in the retina of newborn rats

[[File:JNK1.png]]

<pubmed>20544023</pubmed>

<pubmed>20459797</pubmed>

[http://www.advancedcell.com/patients/clinical-trial-information/ Advanced Cell Technology]- A biotechnology company which is currently running two clinical trials that utilise human embryonic stem cell derived retinal pigmented epithelial cells. These trials are examining the possibility of using these cells to treat stargardt's macular dystrophy and dry age-related macular degeneration<ref><pubmed>22281388</pubmed></ref>.

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===LRP5 is required for vascular development in deeper layers of the retina===

<pubmed>20652025</pubmed>

{| width=800px
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|
The lipoprotein receptor-related protein 5 (LRP5) has a significant function in the development of retinal vasculature.<ref name="PMID20652025"><pubmed>20652025</pubmed></ref> Research has shown that mutations of the LRP5 causes loss of function, due to incomplete development of retinal vessel network, in both humans and mice. The authors investigated how mutations occur in the LRP5, which leads to abnormal development of the retinal vasculature. They have studied retinal endothelial cells in mutant mice in their study. Their results showed that in retina with mutated LRP5, endothelial cells in the retinal vasculature primarily produced cell clusters in the inner-plexiform layer instead of migrating into deeper layers of the retina to form normal retinal vasculature. The authors also discovered that there was a decrease in Slc38a5, which is a “a Müller cell-specific glutamine transporter”, in mice with mutated LRP5. Their results lead the authors to conclude that normal LRP5 is very important in the development of normal retinal vasculature due to their role in causing migration of retinal endothelial cells in the deeper layers of the retina. LRP5 is also important for retinal interneurons and Müller cells to function correctly.

|
[[File:Retina-cell-clusters.JPG|350px|thumbnail|'''Endothelial cells form thick clusters in the LRP5 mutant retina''']]
|}

-----------------

==Useful Links==

{{External Links}}

[http://www.youtube.com/watch?v=Xme8PA6xv-M Visualisation of eye development in the embryo]

[http://www.embryo.chronolab.com/sense.htm Embryonic Development of the eye]

==Glossary==

'''Accommodation''' - changing the focal length of the lens in order to focus on an object.

'''Downstream genes''' - genes that are activated by other "upstream genes".

'''Ectoderm''' - outermost layer of germ cells in an early embryo.

'''Endoderm''' - innermost layer of germ cells in an early embryo.

'''Glial cells''' - non-neuronal cells that provide structure and protection to neurons as well as producing myelin.

'''Inductive signaling''' - a process whereby the secretion of factors from one cell or tissue triggers a response in another.

'''Lens vesicle''' - the cavity of invaginated ectoderm from the optic placode that will form the lens.

'''Macula''' - a highly pigmented, oval-shaped area located near the centre of the retina. Important for visual acuity.

'''Mesenchyme''' - undifferentiated, loose connective tissue.

'''Mesoderm''' - middle layer of germ cells in an early embryo.

'''Mesothelium''' - the epithelial layer of the mesoderm.

'''Myelinisation''' - development of a myelin sheath around a nerve fibre.

'''Neural crest''' - a portion of the ectoderm situated next to the neural tube.

'''Neural groove''' - a large invagination on the dorsal surface of the embryo which will close off and form the neural tube.

'''Neural tube''' - hollow structure that results from the folding of the neural plate and eventually forms the central nervous system.

'''Neuroblastic layer''' - a layer of immature cells that differentiate to form either glial cells or neurons. The retina has two of these (an inner and outer).

'''Neuroectoderm''' - portion of the ectoderm that develops to form the central and peripheral nervous systems.

'''Optic chiasm''' - the point at which the optic nerves meet and cross over.

'''Optic cup''' - the structure that is formed after the optic vesicle folds in upon itself. This will form the retina.

'''Optic globe''' - a term that refers to the optic cup, lens vesicle and surrounding mesenchyme collectively.

'''Optic placode''' - area of thickened ectoderm that gives rise to the lens of the eye.

'''Optic stalk''' - a long, narrow cavity that will produce the optic nerve.

'''Optic vesicle''' - a cavity that buds off from the neural tube and gives rise to the optic cup.

'''Upstream genes''' - genes that activate one or more other "downstream genes".

'''Vascularise''' - to invade with blood vessels.

==Image Gallery==
<gallery>
Image:Eye_diagram_bandw.jpg‎ | Basic structure of the human eye.
Image:Stage14 sem2b-limb.jpg | A Stage 14 embryo showing the location of an otic placode.
Image:Stage 13 image 060.jpg | A cross section showing the organisation of the developing brain, the optic vesicle and the lens (optic) placode.
Image:Formation of the optic vesicle 1.jpg | Early formation of the optic vesicle from the neural groove.
Image:Formation of the optic vesicle 2.jpg | The optic vesicle at a later stage, showing the optic stalk.
Image:Formation of the optic nerve and chiasm 1.jpg | A recognisable brain and eye structure in later development.
Image:Formation of the optic cup 1.jpg | Mechanism of optic cup formation.
Image:Formation of the optic cup 2.jpg | Layers of the optic cup in retina development.
Image:Formation of the retina 1.jpg | Cross-section of the primitive retina showing cell types and layers.
Image:Formation of the retina 2.jpg | Cross-section of a developed retina showing cell types and layers.
Image:Formation of the lens 1.jpg | The importance of the optic cup in lens differentiation.
Image:Formation of the lens 2.jpg | The lens placode separates from the ectoderm and migrates into the mesoderm forming the lens vesicle.
Image:Formation of the choroid and sclera 1.jpg | The choroid and sclera derives from mesenchyme surrounding the optic cup.
Image:Formation of the eyelid 1.jpg | Small grooves in the ectoderm of the head - the precursors to an eyelid.
Image:Formation of the eyelid 2.jpg | The eye at an advanced stage of embryonic development. Note however, that the eyelids remain fused until much later.

</gallery>

==References==
<references/>

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--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

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{{2012Projects}}

2012 Group Project 1

2012-10-02T04:26:36Z

Z3254758: /* Cornea */

[[File:Eye_collage_2.jpg|right|830px]]

=Vision Development=

==Introduction==

Eyes are an important sensory organ shared across many different species and allow organisms to gather useful visual information from their environment. The visual system uses light from the environment and processes this information in the brain for visual perception. The visual system is complex, and is made up of various structures that work together to form vision. Each of the structures in the eye have specific tasks which contribute to the visual system. Knowledge of how the eye develops extends as far back as Aristotle more than 2000 years ago, and current knowledge shows that most of the crucial events of eye development occur in the embryological stage. The eye is an interesting model for studying the development of tissues in organisms, as it consists of cells from several parts of the embryo including the head ectoderm, neural ectoderm and mesoderm. From its many origins the cells come together and differentiate to produce the complex organ that is the eye. During this period there are many examples of inductive signaling, as the tissues coordinate their development throughout this elegant process.

The main anatomical structures of the eye are as follows:
{|
|
* Cornea

* Sclera

* Choroid

* Iris

* Ciliary body

* Lens

* Anterior chamber

* Posterior chamber

* Retina

* Optic nerve

|[[File:eye_diagram_bandw.jpg|right|250px|thumb|Basic structure of the human eye.]]
|}
[[File:Eyediagramcolour1.JPG|550px]]

==Research History==

=== '''Brief Timeline of Historical Developments on the Eye and its Embryology''' ===

{| width=800px
|-bgcolor="CEDFF2"
| width=100px|'''Time'''
| width=700px|'''Discovery'''

|-
| '''Ancient Egyptians'''
| First to document cataracts. It is described as being 'the white disease of the eye' or 'darkening of the pupil.' <ref>Edwards, D.D. (1996). Ophthalmology before Hippocrates. In the History of Ophthalmology, ed. D.M. Albert and D.D. Edwards. Cambridge, Mass.: Blackwell Science.</ref> The Egyptians had some knowledge of the eye, however it is not known how much of the anatomy of the eye was known in their era.

|-bgcolor="F5FAFF"
| '''535 BC'''

|
Ancient Greek philosopher Alcmaeon conducted dissection of humans for the first time in recorded history. This included dissection of the eye. However, not much is known about which anatomical features he discovered. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17.">Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17.</ref>

|-
| '''384- 322 BC'''

| [[File:Aristotle-eye.jpg|200px|thumbnail|The eye according to Aristotle.<ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "> Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau </ref> Note the lens is missing, and there are three vessels drawn that was believed to transport fluid to and from the eye.<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
]]
Aristotle performed dissections of animal embryos.<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

When Aristotle described the embryo of a ten day old chicken, he wrote "The eyes about this time, if taken out, are larger than beans and black; if their skin is removed the fluid inside is white and cold, shining brightly in the light, but nothing solid." <ref name="Magnus, H. (1998). Ophthalmology of the ancients. In J. Hirschberg (Ed.), The History of Ophthalmology: The monographs, Vol. 4, Part 1 (F.C. Blodi, Trans.) Bonn: Wayenborgh.">Magnus, H. (1998). Ophthalmology of the ancients. In J. Hirschberg (Ed.), The History of Ophthalmology: The monographs, Vol. 4, Part 1 (F.C. Blodi, Trans.) Bonn: Wayenborgh.</ref>

Aristotle believed that the eyes started forming during early embryogenesis, however, he also believed that the eyes are the last organs to form completely, and he incorrectly thought that the eyes shrink in later embryonic development. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press.">Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press.</ref> .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="F5FAFF"
| '''340 BC'''

| Lens is thought to have been discovered by Hippocrates, due to his descriptions of the contents of the internal eye There has been studies in chick development later on by followers of Hippocrates. They claimed that eyes were visible in early embryogenesis. .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
|-
|'''25 BC - 50 AD'''

| [[File:Celsus-eye.jpg|150px|thumb|The eye according to Celsus. <ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "/>
Note the lens is placed in the centre of the eye, in the vitreous.<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> ]]

Aulus Cornelius Celsus wrote a Roman medical text called 'De Medicina' in which he wrote that the lens was the part of the eye from which vision originated. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.">Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.</ref> Celsus also incorrectly drew the lens in the center of the globe in his diagram of the eye. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

|-bgcolor="F5FAFF"
| '''23-79 AD '''
|
Pliny the Elder said that the eye is the last of the organs to develop in the womb <ref name="Magnus, H. (1998). Ophthalmology of the ancients. In J. Hirschberg (Ed.), The History of Ophthalmology: The monographs, Vol. 4, Part 1 (F.C. Blodi, Trans.) Bonn: Wayenborgh."/>
|-
| '''98-117 AD'''

| [[File:Rufus-eye.jpg|150px|thumb|The eye according to Rufus of Ephesus. <ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "/>
Note the lens is placed in the correct position, behind the iris of the eye <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> ]]

Rufus of Ephesus identified the lens as being located in the anterior part of the eye, close to the pupil. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

His diagram illustrates that he knew the correct position of the lens as being directly behind the iris, in the anterior part of the eye, and not in the centre as was previously depicted by others before him.

|-bgcolor="F5FAFF"
| '''130-200 AD'''

| [[File:Galen-eye1.jpg|150px|thumb|The eye according to Galen. <ref name="Magnus,H., (1901). Die Augenheilkunde der Alten, Breslau "/> ]]

Claudius Galen practised medicine in Rome. He wrote:

"1. Within the eye the principal orgran of sensation is the crystalline lens.

2. The sensation potential comes from the brain and is conducted via the optic nerves.

3. All other parts of the eyeball are supporting structures." <ref> Hirschberge, J. (1982). Antiquity, Vol. X in the History of Ophthalmology (F.C. Blodi, Trans.) Bonn: Wayenborgh. pp. 280 </ref>

Galen thought that the lens was produced from the vitreous. He also believed that the retina’s function was to give nourishment to the lens and vitreous, and to carry visual information to the brain from the lens. <ref name="Albert, D.M. (1996). Greek, Roman and Arabian Ophthalmology. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

|-
| '''1514-1564'''

| Andreas Vesalius published his anatomy book "De Humani Corporis Fabrica in 1543. He had the misconception that the lens was located in the centre of the eyeball. .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> He also wrote that the lens functioned "like a convex lens made of glass" <ref name="Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.">Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science.</ref> pp. 48
|-bgcolor="F5FAFF"
| '''1535-1606'''

| Georg Bartisch correctly drew a diagram of the lens placed behind the iris in his book 'Ophthalmodouleia: das ist Augendienst'. <ref name="Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>
|-
| '''1537-1619'''

| Fallopio Hieronymus Fabricius ab Aquapendente studied anatomy and embryology. He studied chicken embryos, and thought that chalazae (which comes from egg white) gives rise to the eyes. He also drew the lens directly behind the iris in a diagram in is book 'Tractatus de Oculo Visuque Organo. <ref name="Albert, D.M. (1996). Discovering the anatomy of the eye. In D.M. Albert and D.D. Edwards (Eds.), The History of Ophthalmology. Cambridge, MA: Blackwell Science."/>

|-bgcolor="F5FAFF"
| '''1583'''

| Felix Platter published his book 'De corporis Humani Structura et Usu, after he performed dissections of human bodies. He believed that the retina is the primary visual organ in the eye. .<ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-
| '''1619'''
| Scheiner is given credit to be the first person to correctly draw the diagram of the anatomy of the eye. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
|-bgcolor="F5FAFF"
| '''1672'''
| Marcello Malpighi described the embryonic development of the chicken. He drew many detailed diagrams of the chick eye. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-
| '''1665'''
| Nicolaus Steno identified the choroid fissure in his study of a developing embryo of a chicken. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1754'''

| Albrecht von Haller studied the embryology of the eye. With help from his student Johann Gottfried Zinn, he contributed to the understanding of the development of the ciliary body, ciliary zonule, and their relationship with the lens and vitreous. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-
| '''1817'''

| Christian Pander discovered the three embryonic germ layers, which he wrote about in his book. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/> Pander was the first to think of 'the optic vesicles as lateral evaginations' of the 'prosencephalon'; however, he was incorrect about the details regarding how 'the eye develops from these evaginations'. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-bgcolor="F5FAFF"
| '''1828-1837'''

| Karl Ernst von Baer studied embryology. He discovered that the optic vesicles were 'outgrowths of the embryonic forebrain' <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> which he believed was caused by pressure from fluids in the central nervous system. Von Baer also believed that the optic vesicle opens to form the pupil, and that fluid in the optic vesicle coagulates to form the vitreous body and lens. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-
| '''1830'''

| Emil Huschke discovered that the lens forms from the invagination of the surface ectoderm. He concluded that the lens hence does not form ‘from the fluid of the optic vesicle’ <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> as previously thought.
|-bgcolor="F5FAFF"
| '''1832'''

| Emil Huschke wrote in his manuscript ‘Ueber die erste Entwinkenlung des Auges und die damit zusammenhängende Cyklopie’ that the lens capsule forms from the outer surface ectoderm, which detaches and moves back inward, which is later enclosed again by several membranes, such as by the cornea. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

Huschke also described how the optic cup and choroid fissure forms. He discovered that the optic vesicles are produced from the two-layered optic cup. However, he incorrectly described the destiny of the ‘individual optic cup layers’. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/> <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

|-
| '''1838'''
| Matthias Jakob Schleiden and Theodor Schwann formulated the ‘cell theory’: “All living things are formed from cells, the cell is the smallest unit of life, and cells arise from pre-existing cells.” <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>
|-bgcolor="F5FAFF"
| '''1839'''

| Theodor Schwann contributed a better understanding of the development of the lens through studying the foetus of a pig, which he wrote about in his book ‘Mikroskopische Untersuchungen Über Die Uebereinstimmung in Der Struktur Und Dem Wachsthum Der Thiere Und Pflanzen’. He wrote that the lens is made of ‘concentric layers’ of fibres which proceeds from an anterior to posterior direction. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>
|-
| '''1842'''
| Robert Remak gave the current names to the three embryonic germ layers: ectoderm, mesoderm and endoderm. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="F5FAFF"
| '''1843'''
| Wilhelm Werneck published his book ‘Beiträge zur Gewebelehre des Kristallkörpers’. He wrote that the contents inside of the lens is not made of fluids, as was previously believed. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/> Werneck also discovered that the fibers of the lens continues to grow from the outside to the centre during embryogenesis. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

|-
| '''1855'''

| Robert Remak wrote his book ‘Untersuchungen über die Entwickelung der Wirbelthiere’. He wrote about what he discovered in his studies of the development of the eye in the embryos of chickens, frogs, and rabbits. He wrote very descriptively about the embryology of lens formation, amongst other topics. He discovered that the ectoderm gives rise to the lens placode. <ref name="Adelmann, H.B. (1966). Marcello Malpighi and the Evolution of Embryology. Ithaca: Cornell University Press."/>

|-bgcolor="F5FAFF"
| '''1858'''
| Henry Gray published his book 'Anatomy, Descriptive and Surgical'. He had also previously studied the embryonic development of the optic nerve and retina of chickens.
|-
| '''1877'''
| Paul Leonhard Kessler wrote about the embryonic development of the lens in mice in his book ‘Zur Entwickelung des Auges der Wirbelthiere. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="F5FAFF"
| '''1891'''
| Vincenzo Colucci studied newts and discovered their ability to regenerate the lens.<ref> Tsonis, P. A. (2001). Regeneration of the Vertebrate Lens and Other Eye Structures. eLS. (Online Publication). DOI: 10.1038/npg.els.0001102 </ref>
|-
| '''1892'''
| Dr. Oscar Hertwig published his book ‘Text-Book of the Embryology of Man and Mammals. <ref> Hertwig, O. Text-book of the embryology of man and mammals. S. Sonnenschein 1901. (Translated from the 3d German ed. by Edward L. Mark.) </ref> It contains a very detailed description of the development of the eye, according to the findings at that time. [http://embryology.med.unsw.edu.au/embryology/index.php?title=Book_-_Text-Book_of_the_Embryology_of_Man_and_Mammals_16-2#The_Development_of_the_Eye]
|-bgcolor="F5FAFF"
| '''1895'''
| Gustav Wolff also independently studied newts and discovered their ability to regenerate the lens. .<ref> Tsonis, P. A. (2001). Regeneration of the Vertebrate Lens and Other Eye Structures. eLS. (Online Publication). DOI: 10.1038/npg.els.0001102 </ref>

|-
| '''1900'''
| Carl Rabl published his book ‘Uber den Bau und die Entwicklung der Linse’. He wrote about the development of the lens in mammals, fish, birds, reptiles, and amphibians. <ref name="Lovicu, F.J., & Robinson, M.L. (2004), Chapter 1: The Lens: Historical and Comparative Perspectives, Development of the Ocular Lens, Cambridge University Press, pp. 3-17."/>

|-bgcolor="F5FAFF"
| '''1901'''
| Hans Spemann published his findings from his experimental studies about the formation of the lens in the frog. He found that the optic cup needed to be in contact with the ectoderm for normal development of the eye. <ref> Spemann, H. (1901). Über Correlationen in der Entwicklung des Auges. Verhand. Anat. Ges. 15: 61-79. </ref> <ref> Saha, M. (1991). Spemann seen through a lens. In Gilbert, S. F. (ed.). A Conceptual History of Modern Embryology. Plenum Press, NY. pp. 91-108.</ref>
|-
| '''1906'''
| Brown ‘s book “The Embryology Anatomy and Histology of the Eye” was published. It contained detailed descriptions of the embryonic development of the eye according to the knowledge current at that time, mainly based on observations from embryos of rabbits and chickens. <ref> Brown, E.J. (1906). The Embryology Anatomy and Histology of the Eye. Chicago: Hazlitt & Walker. 1906 </ref>

|-bgcolor="F5FAFF"
| '''1907'''

| John Clement Heisler published his book ‘A Text-book of embryology’. It contains a chapter detailing the embryonic development of the eye, according to the knowledge current at that time. The book’s copyright has expired, so it can be viewed free online: [http://archive.org/details/atextbookembryo01heisgoog]

Julius Kollman also published his book 'Atlas of the Development of Man'. It contained very detailed description and illustrations showing the embryonic development of the human according to the knowledge current at that time. His illustrations were reused by many others after his time and built upon for further refined understanding of the embryology of the human.

Here are examples of Julius Kollman's excellent illustrations showing eye development in various stages:

'''Formation of Primary Optic Vesicle:'''
<gallery>
File:Kollmann691.jpg|The blue part at the bottom is the endoderm. The pink middle layer is the mesoderm. The top yellow layer is the ectoderm. The fold labelled as 'augenfeld' is the place where the optic vesicle will form.
File:Kollmann692.jpg|The eye area (augenfeld) is a bowl shaped bulge still located on the side walls.
File:Kollmann693.jpg| The neural tube is shown after removal of all of the ectoderm and ventral organs, such as heart, gut tube, etc. The primary optic vesicle forms a slightly flattened hollow protrusion on the forebrain.
File:Kollmann694.jpg|The lateral surface of the primary optic vesicle is slightly depressed, showing the first sign of the emergence of the secondary optic vesicle
</gallery>

'''Development of Lens:'''

<gallery>
File:Kollmann695.jpg|The bulging lateral wall of the primary optic vesicle is covered by a fairly well demarcated lens plate, a direct continuation of the ectoderm. Between the optic vesicle and the lens pit are some flattened spindle-shaped cells. In the adjoining mesoderm are cross-sections of capillaries.
File:Kollmann697.jpg|The lens still hangs together with the ectoderm. The primary eye vesicle is indented with respect to the lens. Between the lens and the lateral plate of the optic vesicle is a narrow space, which allows area to further develop later.
File:Kollmann698.jpg|4th Week of development. The internal organisation shows the secondary optic vesicle. A: The rear wall of lens is noticeable and is enveloped by mesoderm. B: The edges of the lens pit is already grown and the lens vesicles are formed, which is still related to the remaining ectoderm.
File:Kollmann699.jpg|The lens has now cut off from the ectoderm, but is still very superficial. Between it and the lateral lamina of the optic cup, there is a considerable space. The eye stalk has become longer and is enclosed together with the optic cup and lens of the mesoderm. The cornea, sclera and choroid make gradual development.
</gallery>

|-
| '''1921'''
| Bailey and Miller published their textbook “Text-Book of Embryology “. <ref> Bailey, F.R. and Miller, A.M. (1921). Text-Book of Embryology. New York: William Wood and Co. (Note- This book is only at an early edited stage)</ref> It contains detailed description of the development of the embryonic eye according to the knowledge current at that time. [http://embryology.med.unsw.edu.au/embryology/index.php?title=Book_-_Text-Book_of_Embryology_18]

|-bgcolor="F5FAFF"
| '''1925'''

| Mann published his research article, in which he gives a detailed account of the development of the human iris. He divided the development of the iris into four stages: weeks 4-7 (before the ectodermal iris forms or before the anterior chamber forms); weeks 7-11 (anterior chamber appears, and mesodermal iris forms); weeks 11-12 (ectodermal iris forms); 3-8 months (muscles of the pupil forms from ectodermal iris, and the central portion of the mesodermal iris atrophies to make the pupil clear). <ref name="PMID18168466"><pubmed>18168466</pubmed></ref>
O Leser also published an article detailing the development of extraocular muscles in mammals he studied. <ref name="PMID18168498"><pubmed>18168498</pubmed></ref>

|-
| '''1939'''
| Holtfreter <ref> Holtfreter, J. (1939). Gewebeaffinitat, ein Mittel der embryonalen
Formbildung. Arch. Exp. Zellforsch. 23, 169-209. </ref> studied amphibians and observed that that the development of the eye stops at the ‘optic vesicle stage’ if there is no contact ‘with the epidermis and neural crest driven mesenchyme’. <ref name=”PMID11023863”><pubmed>11023863</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1955'''
| Barber published his book ‘Embryology of the human eye’. <ref> Barber AN: Embryology of the human eye. St. Louis. CV Mosby 1955</ref> In contains detailed descriptions of the embryological development of the human eye according to the knowledge current at that time. It contains many photographs of the eye at different stages of development.

|-
| '''1957'''
| Coulombre studied a chicken embryo to find the role of intraocular pressure in the development of the chick’s eye, especially in regards to its control of the size of the eye structures. <ref name="PMID13469954"><pubmed>13469954</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1958'''
| Coulombre studied the development of the cornea and how it develops its transparency. <ref name="PMID13563560"><pubmed>13563560</pubmed></ref> He also studied the development of corneal curvature. <ref name="PMID 13519969"><pubmed> 13519969</pubmed></ref>

|-
| '''1962'''
| Coulombre studied the development of the conjunctival papillae and scleral ossicles. <ref name="PMID 14023393"><pubmed> 14023393</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1963'''
| Coulombre studied the development of lens fibers and their orientation. <ref name="PMID14077035"><pubmed>14077035</pubmed></ref> He also studied the development of pigmented epithelium. <ref name="PMID14023394"><pubmed>14023394</pubmed></ref>

|-
| '''1964'''

| Coulombre further studied the development of the lens to determine the role of the lens in eye growth. <ref name="PMID14189921"><pubmed>14189921</pubmed></ref> He also studied the role of thyroid in the development of the cornea and the development of corneal transparency. <ref name="PMID14211912"><pubmed>14211912</pubmed></ref> Mann also published his work called ‘The development of the human eye’, which contains detailed description of the embryonic development of the eye according to current knowledge at that time. <ref> Mann I. The development of the human eye. New York: Grune and Stratton 1964</ref>

|-bgcolor="F5FAFF"
| '''1965'''
| Coulombre published his findings regarding the regeneration of the neural retina from pigmented epithelium in the embryo of chickens. <ref name="PMID5833111"><pubmed>5833111</pubmed></ref> Smelser also published his findings on the embryological development and morphology of the lens. <ref name="PMID14340157"><pubmed>14340157</pubmed></ref>

|-
| '''1966'''

| Formation of the face and orbit occurs from the differentiation of neural crest cells. <ref name="PMID5969670"><pubmed>5969670</pubmed></ref> O’Rahilly also published findings of the development of the eye in the early stages of human embryos. <ref> O'Rahilly, R. 1966 The early development of the eye in staged human embryos. Contr. Embry. Carnegie Inst., Wash., 38: 1–42</ref>

|-bgcolor="F5FAFF"
| '''1968'''
| Findings of the postnatal development of the retina of rats was published. <ref name="PMID5640327"><pubmed>5640327</pubmed></ref>

|-
| '''1969'''

| Mann again published his work called ‘The development of the human eye’. He stated that that the lens in humans forms completely from the ectoderm. <ref name=”Mann I. The Development of the Human Eye. New York, USA: Grune & Stratton, Inc; 1969”> Mann I. The Development of the Human Eye. New York, USA: Grune & Stratton, Inc; 1969</ref> Coulombre also studied the development of the lens, and took note of its size, shape and orientation throughout its developmental stages. <ref name="PMID 5772716"><pubmed> 5772716</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1970'''
| Coulombre again further studied the regeneration of the neural retina from pigmented epithelium of embryos of chickens. <ref name="PMID 5472476"><pubmed> 5472476</pubmed></ref>

|-
| '''1971'''

| Coulombre further studied the development of the lens. This time he focused on analysing the histological mechanisms in the reconstitution of the lens from implanted lens epithelium. <ref name="PMID 4925671"><pubmed> 4925671</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1973'''
| A research article was published, detailing the embryonic development of the retina of humans. <ref name="PMID 6650859"><pubmed> 6650859</pubmed></ref>

|-
| '''1976'''

| Geeraets published his observations of the closure of the embryonic optic fissure in golden hamsters, using the electron microscope. <ref name="PMID 1266776"><pubmed> 1266776</pubmed></ref> Kornneef also published an article based on his studies of the development of connective tissue in the human orbit. <ref name="PMID 1020699"><pubmed> 1020699</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1981'''
| A research article was published detailing how myelin forms in the optic nerve of humans. <ref name="PMID 7224936"><pubmed> 7224936</pubmed></ref>

|-
| '''1983'''
| O’Rahilly’s further research developments was published, reporting the timing and sequence of events in the development of the embryonic human eye. <ref name="PMID 6650859"><pubmed> 6650859</pubmed></ref>

|-bgcolor="F5FAFF"
| '''1990'''

| Van Driell et al. <ref>Driell, D. Van; Provis, J.M.; Billson, F.A.: Early differentiation of ganglion, amacrine, bipolar and Muller cells in the developing fovea of the human retina. J. Comp. Neurol. 291: 203-219.</ref> studied the manner in which amacrine, bipolar, retinal ganglion cells, and Muller cells differentiate in the developing fovea of the retina of a 15-week old human foetus. <ref name="PMID1628748"><pubmed>1628748</pubmed></ref> Tripathy also published an article providing evidence that the lacrimal glands in humans originates from the neuroectoderm. <ref name="PMID2406219"><pubmed>2406219</pubmed></ref>

|}

==Development, Structure and Function of Ocular Components==

The eye itself is formed from several components; notably the optic placode of the head ectoderm, the optic vesicle from the neural tube, and mesenchyme from the mesoderm and neural crest cells. The optic placode contributes the lens to the eye, the optic vesicle gives rise to layers of the retina, while the mesenchyme will produce the ciliary body, iris, choroid and sclera.<ref>http://www.vetmed.vt.edu/education/curriculum/vm8054/eye/EMBYEYE.HTM</ref> Cells from the neural tube will also produce the optic nerve, which receives nerve impulses from the retina of the eye. Eyes initially form as laterally paired structures and migrate medially in the human embryo. In other animals such as birds and lizards, the eyes do not migrate and develop laterally on the head. The optic placodes become prominent on the surface of the embryo at approximately Stage 14 of development.

[[File:Stage14 sem2b-limb.jpg|200px|thumb|left|A Stage 14 embryo showing the location of an otic placode.<ref name="http://embryology.med.unsw.edu.au/embryology/index.php?title=ANAT2341_Lab_6_-_Early_Embryo">http://embryology.med.unsw.edu.au/embryology/index.php?title=ANAT2341_Lab_6_-_Early_Embryo</ref>]] [[File:Stage 13 image 060.jpg|400px|thumb|center|A cross section showing the organisation of the developing brain, the optic vesicle and the lens (optic) placode.<ref name="http://embryology.med.unsw.edu.au/embryology/index.php?title=ANAT2341_Lab_6_-_Early_Embryo"/>]]

===Optic Nerve===

The optic nerve consists of nerve fibres that transmit information from the retinal photoreceptor cells to the brain. The optic nerve is formed from the optic stalk, which develops as the optic vesicle migrates from its origin in the neural tube to its destination - the surface ectoderm - where it will fuse with the optic placode (also known as the lens placode, which will contribute the lens to the eye).<ref name="PMID11687490"><pubmed>11687490</pubmed></ref>

[[File:Formation of the optic vesicle 1.jpg|400px|thumb|left|Fig. 1: Early formation of the optic vesicle from the neural groove.]] [[File:Formation of the optic vesicle 2.jpg|400px|thumb|center|Fig. 2: The optic vesicle at a later stage, showing the optic stalk.]]

As can be seen in Figure 1 above, the optic vesicle forms from the neural tube. However, note that the neural tube has not yet closed, and is still the neural groove at this point. Figure 2 then shows the optic vesicle at slightly later stage in the same simplified cross-section of the embryo, as it migrates from the neural tube to the surface ectoderm. Note the presence of the optic stalk which links the optic vesicle to the neural tube. Later in development, this primitive structure will become the optic nerve, which will link the eye to the brain.

The nerve fibres themselves will initially originate from the retinal ganglion cells in the eye during week 6.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008">Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008</ref> After two weeks, these fibers will have grown along the inner wall of the optic stalk and have reached the brain. They grow both in length and width, with the nerve fibres filling the hollow optic stalk to form the solid optic nerve. More than one million nerve fibers will eventually make up the optic nerve, along with glial cells which arise from the inner wall of the optic stalk itself.<ref><pubmed>1451666</pubmed></ref> Myelinisation of the optic nerve begins much later in development at around 7 months, beginning at the optic chiasm and moving towards the eye.<ref><pubmed>7224936</pubmed></ref> The optic chiasm forms just before the nerves reach the brain, and is where half the nerve fibres from each eye will cross over to the opposite side of the brain. This is demonstrated in Figure 3. Note the crossing over of the optic nerves just before they enter the brain, at the optic chiasm. This organisation is now much more familiar, with the eyes near the ectoderm and the optic nerve leading through the mesoderm to the brain buried deep in the embryo.

[[File:Formation of the optic nerve and chiasm 1.jpg|400px|thumb|center|Fig. 3: A recognisable brain and eye structure in later development.]]

===Retina===

The retinal component of the eye is formed when the optic vesicle folds in upon itself, forming the optic cup (see Figure 4). In doing so it creates two layers - an inner wall and an outer wall of the optic cup (Figure 5). These two layers of the optic cup will give rise to the two layers of the retina - the inner neural retina, and the outer pigmented epithelium.<ref name="PMID11687490"/> Note the existence of the space between the two layers of the retina. This is known as the intraretinal space and disappears by the 7th week of development, however the two layers never completely fuse and can become separated as a result of physical trauma to the head - leading to a detached retina and loss of vision.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/>

The inner wall of the optic cup, which will give rise to the neural retina, consists of a layer of pseudostratified cells (see Figure 6) that later differentiate into rod, cone, bipolar, ganglion, horizontal, amacrine and glial cells of the retina (Figure 7).<ref name="PMID18168748"><pubmed>18168748</pubmed></ref> The outer wall of the optic cup consists of a layer of cuboidal cells that contain melanin - the light absorbing pigment. The function of this layer is to absorb light and prevent internal reflection of light within the eye, which would impair our ability to form distinct images. Interestingly, in some animals such as cats, this layer actually reflects light intentionally to increase the amount of light available to the eye in low-light conditions. This is why cats seem to have eyes that glow in the dark.<ref>http://dialspace.dial.pipex.com/agarman/bco/fact4.htm</ref>

[[File:Formation of the optic cup 1.jpg|400px|thumb|left|Fig. 4: Mechanism of optic cup formation.]] [[File:Formation of the optic cup 2.jpg|400px|thumb|center|Fig. 5: Layers of the optic cup in retina development.]]

The inner wall itself is divided into two components - the inner neuroblastic layer and the outer neuroblastic layer (see Figure 6). The outer neuroblastic layer forms the rod and cone cells while the inner neuroblastic layer forms the remaining cell types found in the retina - the bipolar, ganglion, horizontal, amacrine and glial cells (Figure 7).<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/> The organisation of the retina is interesting in that incoming light passes through several layers of these neural retina cells before it is detected by rod and cone cells at the back of the retina, and then nerve signals are passed back through the layers of neural retina cells that the light just passed through moments before - a seemingly strange design that the eye does not share with man-made light-capturing devices such as a camera (imagine putting the wires in front of the image sensor!).

Differentiation of the neuroblastic layers into neural retina cells occurs in a pattern both within the layers and across the retina. Cells differentiate from the inner neuroblastic layer to the outer neuroblastic layer, and differentiate from the central retina to the peripheral retina.<ref name="PMID18168748"/> The macula is first identifiable in week 22 when ganglion cells start to form multiple rows, and the primitive fovea begins to form at approximately the same time as a depression in the macula.<ref><pubmed>6462623</pubmed></ref> It is not until 15-45 months after birth that this area becomes exclusively populated by cone cells and becomes the fovea centralis - the area of the retina with the highest visual acuity.

[[File:Formation of the retina 1.jpg|400px|thumb|left|Fig. 6: Cross-section of the primitive retina showing cell types and layers.]] [[File:Formation of the retina 2.jpg|400px|thumb|center|Fig. 7:Cross-section of a developed retina showing cell types and layers.]]

===Ciliary Body===

The ciliary body consists of ciliary processes and three portions of fibres that constitute the ciliary muscles. It functions to maintain normal eye physiology as well as playing a direct role in accommodation.

During development, the ciliary processes form slightly posterior to the iris, developing from part of the anterior rim of the optic cup. It is thought that the folded structure of the ciliary processes is brought about by intraocular pressure and specific signalling pathways.<ref name="PMID16959249"><pubmed>16959249</pubmed></ref> While the ciliary muscles and the endothelial cells of the ciliary blood vessels are chiefly formed by mesenchymal cells<ref><pubmed>16249499</pubmed></ref>, the neural crest and neuroectoderm also contribute to their development.<ref><pubmed>12127103</pubmed></ref> The normal development of the ciliary body is dependent on the correct expression of bone morphogenetic protein (BMP)-4, which is a member of the transforming growth factor-β superfamily.<ref><pubmed>1222340</pubmed></ref> Napier and Kidson (2007) summarised numerous genes that have been associated with ciliary body development, however their direct roles have not been well documented.<ref name="PMID16959249"/>

===Iris===

The iris is a thin layer that develops at the end of the third month of development and is derived from the anterior rim of the optic cup. The stroma of the iris develops from cells of neural crest cell origin.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/> The muscles that are responsible for the dilation and constriction of the pupil (dilator pupillae and sphincter pupillae muscles) form from the neuroectoderm of the optic cup. These cells are initially epithelial cells that then transform into smooth muscle cells. The final colour of the iris is not evident until the postnatal period.<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"></ref>

===Lens===

The lens has its origin from the optic placode, which develops on the ectodermic surface of the embryo and migrates both medially and inwards into the embryo. The lens allows accommodation of the eye, and adjusts its thickness in order to focus on near or far objects. The study of lens development was one of the first to highlight the importance of inductive signaling in development, with Spemann's pioneering work at the start of the 20th century, finding that the absence of retinal development resulted in the absence of lens formation.<ref name="PMID11687490"/> Indeed, it has been consistently shown that the interaction of the migrating optic vesicle with the surface ectoderm of the head is vital in producing differentiation of the lens.<ref name="PMID15558475"><pubmed>15558475</pubmed></ref> The mechanism of interaction is complex but basically involves upstream genes switching on downstream genes, with the genes eventually producing specialised proteins which constitute the lens. The whole process starts with the signaling molecules from the optic cup initiating a thickening of the surface ectoderm of the head (Figure 8). It is thought that this region of specific ectoderm is responsive to the signaling molecules, as lens formation is incomplete or absent when ectoderm from the lateral portion of the embryo (i.e. non-head ectoderm) is exposed to the same inductive signaling processes.<ref name="PMID9216064"><pubmed>9216064</pubmed></ref> Pax6 has been shown to be one of the major genes required for differentiation of the lens, which in turn switches on transcriptional genes such as Sox 1, 2 and 3 among others - producing water-soluble proteins called crystallins - responsible for giving the lens its transparency and refractive properties.<ref name="PMID9609835"><pubmed>9609835</pubmed></ref>

[[File:Formation of the lens 1.jpg|400px|thumb|left|Fig. 8: The importance of the optic cup in lens differentiation.]] [[File:Formation of the lens 2.jpg|400px|thumb|center|Fig. 9: The lens placode separates from the ectoderm and migrates into the mesoderm forming the lens vesicle.]]

The lens placode invaginates from the head ectoderm and migrates into the mesoderm (Figure 9). Once this structure (now known as the lens vesicle) is in place opposite the optic cup, the combined structure is referred to as the optic globe and resembles a recognisable eye structure. The lens continues to differentiate further, as mentioned above, through the formation of crystallin proteins, which give the lens its unique properties and allows for the fine control over the degree of refraction that takes place.

===Aqueous Chambers===

There are both anterior and posterior aqueous chambers of the eye which contain aqueous humour. A space develops in the mesenchyme situated between the lens and cornea to form the anterior aqueous chamber. The mesenchyme located superficially to this chamber forms the mesothelium as well as the transparent portion of the cornea.

The posterior chamber develops from a similar space in the mesenchyme, however it is located between the iris and the lens. The anterior and posterior chambers are able to communicate with one another once the papillary membrane vanishes and the pupil is formed. This channel is known as the scleral venous sinus.<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011">Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011</ref>

===Cornea===

The cornea is the transparent, avascular, most anterior portion of the eye. It is responsible for conducting light into the eye and focusing it on to the retina, as well as maintaining the rigidity of the eyeball. It consists of 5 layers- the epithelium, Bowman’s layer, stroma, Descemet’s membrane and the endothelium.

The epithelium and endothelium of the cornea first appear during the 5th week of gestation. The epithelium of the external surface of the cornea is derived from surface ectoderm, while the mesenchyme is derived from the mesoderm<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"/>. The endothelium is a two-cell cuboidal layer which is made up of differentiated neural crest cells that were initially from the optic cup. By week 8 the endothelial cells begin to secrete a basement membrance which later forms Descemet’s membrane<ref><pubmed>6511224</pubmed></ref>. At approximately 16 weeks gestation the Bowman’s membrane begins to form from the thickening of the stroma that is located under the corneal epithelium<ref>Riordan-Eva P, Whitcher JP. Vaughn and Asbury's General Ophthalmology, Lange Medical Books/McGraw Hill. 2004:25–27</ref>. During the third month glycosaminoglycans secreted by fibroblasts form the ground substance of the cornea, with collagen fibrils and keratan sulphate also appearing around this time. Shortly after this tight junctions form between the endothelial cells<ref><pubmed>19481138</pubmed></ref>. Towards the end of the gestational period the cornea becomes larger due to the production of aqueous humor<ref>Yanoff M, Duker JS. Ophthalmology. Mosby; St. Louis, MO: 2004</ref>. The final transparent structure develops because hyaluronidase removes hyaluronic acid, thyroxine causes dehydration of the stroma, and the entire structure becomes avascular<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/>. Numerous genes have been implicated in the development of the cornea, these include, but are not limited to, PAX6, PITX2, FOXC1, MAF, TMEM114, SOX2, OTX2 and BMP4<ref><pubmed>18637741</pubmed></ref>.

===Choroid and Sclera===

The choroid and sclera are adjacent layers that surround the eye and act to vascularise and protect the eye respectively. They are formed from neural crest and mesoderm-derived mesenchyme which condenses around the optic cup and lens vesicle between weeks 5 and 7 of development to form a primitive eyeball structure known as the optic globe.<ref name="Schoenwolf: Larsen’s Human embryology, 4th ed. Churchill Livingstone, An Imprint of Elsevier. 2008"/> Blood vessels first start to appear in the choroid layer at approximately week 15, and arteries and veins can be distinguished by week 23.<ref>Development of the Choroid and Related Structures, K. Sellheyer, Eye (1990) 4, 255-261</ref> Inductive processes are thought to play a vital role during formation of the choroid and sclera; with the retinal pigmented epithelium inducing differentiation of the surrounding mesenchyme while at the same time the neural crest-derived mesenchyme contributing components to the retinal pigmented epithelium such as melanocytes.<ref name="PMID1628748"/> In addition to having functional roles themselves, the primitive choroid and sclera also contribute components to the developing ciliary body and cornea (Figure 10). In the adult eye, the choroid is continuous with the ciliary body and the sclera with the cornea.

[[File:Formation of the choroid and sclera 1.jpg|400px|thumb|center|Fig. 10: The choroid and sclera derives from mesenchyme surrounding the optic cup.]]

===Eyelids===

The eyelids are ectodermal and mesodermal in origin and are an extension of the skin which covers and protects the eye. Eyelid formation can be first noted during week 5 when small grooves develop in the surface ectoderm (Figure 11).<ref><pubmed>7364662</pubmed></ref> These small grooves deepen and extend into the mesoderm and the primitive eyelid structures grow towards one another, eventually fusing together during week 8.<ref name="Moore: The Developing Human, 9th ed. Saunders, An Imprint of Elsevier. 2011"/> It is not until week 26-28 that the eyelids will separate again. The ectoderm reflects over the developing cornea to form the conjunctival sac, a space that is filled by secretions from the lacrimal gland in order to allow smooth motions of the eyelid over the eye and also to clean the cornea and prevent accumulation of particles on the eye that may disrupt vision. By the time the eyelids separate, the eye has all its major components present (Figure 12), and further development consists mainly of growth and vascularisation.

[[File:Formation of the eyelid 1.jpg|400px|thumb|left|Fig.11: Small grooves in the ectoderm of the head - the precursors to an eyelid.]] [[File:Formation of the eyelid 2.jpg|400px|thumb|center|Fig. 12: The eye at an advanced stage of embryonic development. Note however, that the eyelids remain fused until much later.]]

===Lacrimal Glands===

Lacrimal glands initially develop from budding of the conjunctival epithelium near the superolateral portion of the eye. The mesenchymal cells that surround these buds are of neural crest origin, and the budding continues until the mature gland is formed.<ref><pubmed> 9882499</pubmed></ref> These glands are responsible for the production of tears however they do not start to function until 1-3 months after birth.

==Current Research==

===The impact of visible light on the immature retina===

<pubmed>22405869</pubmed>

The authors mentioned in this article <ref name="PMID22405869"><pubmed>22405869</pubmed></ref>
that they were interested in investigating the effect of light on postnatal eye development in mice, because mice are born with fused eyelids, which separate 12 days after birth. Before the eyelids separate, the retina develops in mice with very little radiation from light. It is believed that the darkness plays a role in the development of the retina in mice, which is why their eyelids are fused for 12 days after birth. Therefore the authors were interested to see what effect light would have on postnatal retinal development of mice, with special interest in retinal ganglion cells (RGC). In their experiment, they surgically opened the eyelids on the right eyes of some of the mice to expose them to visible light 12 hours per day, while they left some other mice in the dark after surgical separation of their eyelids. They also kept the left eyes of the mice naturally fused as controls in the experiment. Their results showed that early light exposure in mice causes a decrease in retinal ganglion cells because it affects cellular apoptosis in the retina. The authors also observed that early exposure to light in mice causes lumican mRna transcription to resume and to quickly increase. (Lumican normally stays silent in retina after birth).

---------

===MIP/Aquaporin 0 Represents a Direct Transcriptional Target of PITX3 in the Developing Lens===

<pubmed>21698120</pubmed>

{| width=800px
|-
|PITX3 plays a siginificant role in the development of lens in vertebrates. If there is a deficiency is PITX3, it causes a range of problems in humans such as microphthalmia, Peter’s anomaly, or isolated cataracts. Mutation of PITX3 also causes degeneration of the lens in zebrafish and mice. It is therefore important to understand what factors may affect the decrease in PITX3, as a normal level of PITX3 is needed to maintain normal eye development. The authors wanted to investigate specific genes which are affected by PITX3. Previous research has shown that MIP and Aquaporin causes defects in the lens in both mice and humans. MIP and Aquaporin are targeted by PITX3, so their imbalance is interrelated in the cause of defects in the lens. Therefore it has been previously proven that PITX3 is needed for normal development of the lens. However, there has not been much information previously known regarding the exact effect that PITX3 has, or the specific genes it targets. Since MIP and Aquaporin is common genes found in humans, mice and zebrafish, the authors <ref name="PMID21698120"><pubmed>21698120</pubmed></ref>
chose to study these genes to understand the pathway that PITX3 takes and its exact involvement in the development of the lens. Their results proved that deficiency in MIP and Aquaporin indeed affects normal development of the lens, and it is indeed related to deficiency in PITX3. However, there is still more research needed to understand PITX3 and the genes it interacts with, and their effect in ocular development.

|
[[File:Mip1-expression-in-pitx3.jpg|thumbnail|250px|Analysis of mip1 expression in pitx3-mo and control embryos via in situ hybridization and RT-PCR]]
|}

-----------

<pubmed>22496813</pubmed>

This research <ref name="PMID22496813"><pubmed>22496813</pubmed></ref>
studied c-Jun N-terminal Kinase (JNK) activation in the retina of newborn rats

[[File:JNK1.png]]

<pubmed>20544023</pubmed>

<pubmed>20459797</pubmed>

[http://www.advancedcell.com/patients/clinical-trial-information/ Advanced Cell Technology]- A biotechnology company which is currently running two clinical trials that utilise human embryonic stem cell derived retinal pigmented epithelial cells. These trials are examining the possibility of using these cells to treat stargardt's macular dystrophy and dry age-related macular degeneration<ref><pubmed>22281388</pubmed></ref>.

----

<pubmed>20652025</pubmed>

The lipoprotein receptor-related protein 5 (LRP5) has a significant function in the development of retinal vasculature.<ref name="PMID20652025"><pubmed>20652025</pubmed></ref> Research has shown that mutations of the LRP5 causes loss of function, due to incomplete development of retinal vessel network, in both humans and mice. The authors investigated how mutations occur in the LRP5, which leads to abnormal development of the retinal vasculature. They have studied retinal endothelial cells in mutant mice in their study. Their results showed that in retina with mutated LRP5, endothelial cells in the retinal vasculature primarily produced cell clusters in the inner-plexiform layer instead of migrating into deeper layers of the retina to form normal retinal vasculature. The authors also discovered that there was a decrease in Slc38a5, which is a “a Müller cell-specific glutamine transporter”, in mice with mutated LRP5. Their results lead the authors to conclude that normal LRP5 is very important in the development of normal retinal vasculature due to their role in causing migration of retinal endothelial cells in the deeper layers of the retina. LRP5 is also important for retinal interneurons and Müller cells to function correctly.

[[File:Retina-cell-clusters.JPG]]

==Useful Links==

{{External Links}}

[http://www.youtube.com/watch?v=Xme8PA6xv-M Visualisation of eye development in the embryo]

[http://www.embryo.chronolab.com/sense.htm Embryonic Development of the eye]

==Glossary==

'''Accommodation''' - changing the focal length of the lens in order to focus on an object.

'''Downstream genes''' - genes that are activated by other "upstream genes".

'''Ectoderm''' - outermost layer of germ cells in an early embryo.

'''Endoderm''' - innermost layer of germ cells in an early embryo.

'''Glial cells''' - non-neuronal cells that provide structure and protection to neurons as well as producing myelin.

'''Inductive signaling''' - a process whereby the secretion of factors from one cell or tissue triggers a response in another.

'''Lens vesicle''' - the cavity of invaginated ectoderm from the optic placode that will form the lens.

'''Macula''' - a highly pigmented, oval-shaped area located near the centre of the retina. Important for visual acuity.

'''Mesenchyme''' - undifferentiated, loose connective tissue.

'''Mesoderm''' - middle layer of germ cells in an early embryo.

'''Mesothelium''' - the epithelial layer of the mesoderm.

'''Myelinisation''' - development of a myelin sheath around a nerve fibre.

'''Neural crest''' - a portion of the ectoderm situated next to the neural tube.

'''Neural groove''' - a large invagination on the dorsal surface of the embryo which will close off and form the neural tube.

'''Neural tube''' - hollow structure that results from the folding of the neural plate and eventually forms the central nervous system.

'''Neuroblastic layer''' - a layer of immature cells that differentiate to form either glial cells or neurons. The retina has two of these (an inner and outer).

'''Neuroectoderm''' - portion of the ectoderm that develops to form the central and peripheral nervous systems.

'''Optic chiasm''' - the point at which the optic nerves meet and cross over.

'''Optic cup''' - the structure that is formed after the optic vesicle folds in upon itself. This will form the retina.

'''Optic globe''' - a term that refers to the optic cup, lens vesicle and surrounding mesenchyme collectively.

'''Optic placode''' - area of thickened ectoderm that gives rise to the lens of the eye.

'''Optic stalk''' - a long, narrow cavity that will produce the optic nerve.

'''Optic vesicle''' - a cavity that buds off from the neural tube and gives rise to the optic cup.

'''Upstream genes''' - genes that activate one or more other "downstream genes".

'''Vascularise''' - to invade with blood vessels.

==Image Gallery==
<gallery>
Image:Eye_diagram_bandw.jpg‎ | Basic structure of the human eye.
Image:Stage14 sem2b-limb.jpg | A Stage 14 embryo showing the location of an otic placode.
Image:Stage 13 image 060.jpg | A cross section showing the organisation of the developing brain, the optic vesicle and the lens (optic) placode.
Image:Formation of the optic vesicle 1.jpg | Early formation of the optic vesicle from the neural groove.
Image:Formation of the optic vesicle 2.jpg | The optic vesicle at a later stage, showing the optic stalk.
Image:Formation of the optic nerve and chiasm 1.jpg | A recognisable brain and eye structure in later development.
Image:Formation of the optic cup 1.jpg | Mechanism of optic cup formation.
Image:Formation of the optic cup 2.jpg | Layers of the optic cup in retina development.
Image:Formation of the retina 1.jpg | Cross-section of the primitive retina showing cell types and layers.
Image:Formation of the retina 2.jpg | Cross-section of a developed retina showing cell types and layers.
Image:Formation of the lens 1.jpg | The importance of the optic cup in lens differentiation.
Image:Formation of the lens 2.jpg | The lens placode separates from the ectoderm and migrates into the mesoderm forming the lens vesicle.
Image:Formation of the choroid and sclera 1.jpg | The choroid and sclera derives from mesenchyme surrounding the optic cup.
Image:Formation of the eyelid 1.jpg | Small grooves in the ectoderm of the head - the precursors to an eyelid.
Image:Formation of the eyelid 2.jpg | The eye at an advanced stage of embryonic development. Note however, that the eyelids remain fused until much later.

</gallery>

==References==
<references/>

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--[[User:Z8600021|Mark Hill]] 12:22, 15 August 2012 (EST) Please leave the content listed below the line at the bottom of your project page.

----

{{2012Projects}}

File:Eye collage 2.jpg

2012-10-02T03:20:15Z

Z3254758:

These images are courtesy of the US National Eye Institute, National Institutes of Health (NEI/NIH)

http://www.nei.nih.gov/photo/keyword.asp?conditions=Normal+Eye+Images&match=all

'''Copyright Policy'''

Unless otherwise noted, information on the National Eye Institute (NEI) Website is in the public domain. Public domain information may be freely distributed and copied, but, as a courtesy, it is requested that the National Eye Institute be given an appropriate acknowledgement: "Courtesy: National Eye Institute, National Institutes of Health (NEI/NIH)."

When using www.nei.nih.gov, you may encounter documents, illustrations, photographs or other information that has been licensed by private individuals, companies or organizations that may be protected by United States and foreign copyright laws. Transmission or reproduction of these protected items requires the written permission of the copyright owners. For information about the copyright owners of a given graphic, photo or illustration on www.nei.nih.gov; how they can be contacted; and what, if any, use those owners allow of their material; please provide the URL and file name to the NEI Website Manager.

'''Graphics/Photos/Illustrations'''

The NEI Photos, Images and Videos catalog is provided as a source of free audiovisuals. Permission is granted to use these items for educational, news media or research purposes, provided the source for each image is credited. The NEI Photos, Images and Videos catalog may not be used to promote or endorse commercial products or services. Use by non-profit organizations in connection with fundraising or product sales is considered commercial use.

Permission to use NEI website graphics found any place other than the NEI Photos, Images and Videos catalog is granted on a case-by-case basis. Some are public domain, some are created by NEI contractors, some are copyrighted and some are used by NEI with specific permission granted by the owner. Therefore, the logos, photos and illustrations found on the NEI website should not be reused without permission.

For information about the copyright holders of a given photo or illustration on the NEI website; how the owners can be contacted; and what, if any, use those owners allow of their material; please contact the NEI Website Manager and provide the URL, file name, and intended use.

Granting the right to use a graphic from the website does not explicitly or implicitly convey NEI's endorsement of the site where it is used.

Talk:2012 Group Project 1

2012-09-26T01:46:33Z

Z3254758: /* Potential Resources */

{{2012GroupDiscussion}}

--[[User:Z8600021|Mark Hill]] 09:58, 18 September 2012 (EST) This is a recent review on vision. http://jcb.rupress.org/content/190/6/953.full JCB content allows reuse.

*Introduction

*Research history?

*Developmental time line?

*Current research

*Useful links

*Glossary

*Image gallery summary

*References

==Group evaluations==

Use of historic images was good. This is a main point of difference between this project and the rest. They are however not very well integrated into the project page, they feel as if they have simply been pasted there for the sake of inclusion. Perhaps an explanation of their significance could be included as well as how these drawings have lead to more refined understandings of specific structures. The Research History section is also quite interesting although it is very brief and could be improved if it were presented in a more visually appealing manner such as in a colour table.

The development structure and function section is excellent. The text is easy to follow and the student drawn images demonstrate a clear understanding of the processes as well as giving the reader the opportunity to better visualise the different stages of development. Another image which could be included would perhaps be a histological picture (as opposed to a diagram) of the different cell layers of the retina ie. The photoreceptor layer, inner nuclear layer etc. The current research section needs further refinement. I see no reason to simply list some current research articles except for point of reference. What needs to be done is explain how current research has changed or challenged traditional views/concepts. A brief summary of each article listed in this section is also warranted.

All images and relevant ideas appear to be appropriately cited and referenced. Image formatting on the whole is quite good although I think those included in the introduction need to be altered as they skew the text, making the section look awkward and a bit difficult to read.

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The photo at the top of your page is a great choice and makes the site that much more appealing. The only suggestion I would have here is to potentially minimise the photo as it makes the contents section to the left of it hard to read. Your introduction is clear and concise and gives a good description of the eye. A slight adjustment I would make is perhaps to make it slightly longer giving a brief discussion about what is to be discussed on this page. Included in your introduction you have the anatomy of the eye. Firstly, would it be appropriate to include the histology as well, as it appears further down the page you discuss the cells, so perhaps if you gave a brief histological overview that could make the sections below easier for the reader to comprehend. I would probably add to that that if you were to include histology, to put the anatomy and histology into a new section just so it doesn’t clutter the introduction.

Your history, although I’m aware it ins’t finished, would read better if it were in a table and would also bring some more colour to the page. I’m assuming this will come when you finish this section, but it would be wise to include updated examples as well in order to show an adequate progression of the history.

The development section appears to be very thorough which is fantastic. It is rather clear that you have put a lot of research and time into this section. The introduction you have there is well written and again concise which is great. Additionally I like your use of photos just below it to further your explanation and also to break up the text. In regards to your photos, I would suggest perhaps a better description of them and to make sure you include where you got the photo from. If there were an explanation of the photo in simplistic terms, then I think the photos would be really beneficial.

The optic nerve section is well written but it appears to lack references?? In the first 3 paragraphs there are only 2 references. I would probably suggest that this information is backed up by additional sources as well. Also, with your hand drawn pictures (which are good), I would suggest an explanation on them when you open the picture up in another window. Your paragraph describing the 2 pictures, I would probably recommend that it become sintegrated within the text i.e. when you are talking about that part of it then include it there. I just think it would make it flow better that way – like you have done with figure 3.

The retina is good and well set out with pictures. However I noticed that you have used the exact references as before (3, 4)?? It would be really advisable to include many more references than what is listed. The same applies to the images as I said above, but good integration!

The ciliary body appears to be well researched and referenced. From the iris down there appears to be a lack of new references and also looks rather bland - so here I would suggest including additional photos from journal articles you have used. Also, it seems rather brief, I’m wondering whether there is more information about the embryological processes that could be included?

The current research is a good start, but there isn’t much of an explanation of the photo that is included and brief discussion of the research should probably be included. Are there additional research projects to include as well?

Finally, your references ar good but short. The fisrt 2 need to be put in the appropriate format. I would definitely suggest including many more references in order to make your information listed more valid.

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Good introduction, introduces the main components of the eye that will assumedly be focused on when talking about development. More information is needed in the history section however and the images used also need copyright permission.

Wording is simple and understandable, it’s also good to see that you guys have a glossary up so to make it easier to comprehend what is being read. However you need more information under current research. Also you should focus on the other components of the eye other than the Optic nerve and the Retina and add more pictures or diagrams to illustrate what it is you’re explaining.

You should also try using some dot points because reading long paragraphs could get tiring and allow the person to lose focus.

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Vision

Good descriptions of individual features of the eye. But seeing how the current task is the embryological development of the eye, it seems to be the smallest section of your wiki. Possibly a flow chart would be best to demonstrate the text you have in this section. Additionally, the information presented isn’t anything new or hasn’t been learnt in intro anatomy and could go further, as your current research section is still unfinished. Needs more current journal information

The text however in all of the sections is too dense and I feel my concentration waning when reading it. And although you have already an overall picture depicting the eye and it’s anatomical features, maybe for each section highlight the area that is being referred too. The timeline is unfinished and too wordy, needs to be more succinct.

The section of development of the optic nerve was really good, but again needs images to reinforce the text. Glossary and references are good, but need to be expanded. And a timeline of development would be useful.

Summary: text overwhelms the images and isn’t balanced.

Good luck with the rest ☺

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Overall, the key points relating to Vision and it’s development are being addressed at this stage by the page. There are some interesting descriptions that are easy to follow. However, in it’s entirety, the descriptions has to be sieved through in order to extract specific information. For example, the functions of each structure has been included in the development of each structure. While this provides a nice way for information to flow, it can be better received if function was separated from development and put under a separate sub-heading before development.

The history section, being in it’s early stages is off to a good start including some important contributions that date back to ancient times, which I find amazing. However, I would suggest, placing this information in the form of a table because full sentences are not necessary to achieve an understanding. It would also be important to include the specific advancements achieved from each moment, with relation to the eye. For example, what contribution did Aristotle’s dissection of the embryo, make to our understanding of the eye and it’s development? Does the age of the embryo tell us something?

Heading suggestions for the history:

1.TIME/PERIOD

2. HISTORIAN/SCIENTIST

3. EVENT

4. CONTRIBUTION TO OUR UNDERSTANDING OF THE EYE.

Moreover, the inclusion of the historic images are unique to the other groups and hence will spark an interest in readers. In saying this, the use of descriptions and appropriate titles will aid the readers in appreciating them from a contextual point of view.

Additionally, the scattered placement of images on the page makes it difficult to follow certain sections and properly use the images to aid my understanding. I suggest revising the method used and possibly having clear distinctions between images belonging to different sections. I.e. Some run over two sections.

I like how each component of the eye’s development is described separately giving us time to appreciated each one individually. However, the timeline of development is also important and sometimes, two components are dependent on each other for growth and development. This maybe something to consider when editing this section, so that an understanding that the entire process of growth and development overlaps amongst structures. A video might suffice here in place of text. Also, the importance of genes in patterning is not clear.

Current research section needs to built upon, maybe with some simple descriptions of the types of research taking place, their potential applications and limitations as well as the use of images that might help explain the conclusions of the project.
Finally, the glossary needs to be expanded upon but so far the definitions are nice and simple for anyone to understand.

Good luck!

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The huge picture of the eyes at the beginning of the page is perhaps necessaries. The title of the page "vision" introduces readers to the topic pretty thoroughly and comprehensively. A poorly formatted and redundant image is just an eye sore.
An explanation of the images under research history would be fantastic. At the moment it is hard for someone who does not know anything about the eye (myself) to use the images at all.
There is abundant information on the retina and optic nerve, with accompanying hand drawn diagrams, which is great.
The current research section seems underdone, seems to be more a link for me to go find the research myself. A little explanation of some of the current research would make it a more complete page.
Glossary and references well done and helpful.

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Great eye image at the start to capture attention. It's nice to see that it has the correct referencing and copyright.

The introduction is very clear and simple to read. Overall the written content is easy to understand and provides sufficient detail to cover the developmental stages of the eye and associated structures like the optic nerve and lacrimal glands.

The images throughout the project were very useful because they complement the text nicely. The student drawn diagrams made the optic vesicle formation easier to understand. However, I think the labels are a bit small - you can really only read them if you click on them and see the larger version. If you can put some labels on the orientation (such as the ventral side, posterior side, etc), that would be great too. Can you also put a reference as to where you got the information to draw these images from?

The images you got from the 'Atlas of development of man volume 2', can you put the copyright up? Not many textbooks allow using their images but if it is allowed for this book, you should definitely include the copyright there.

Sections that seemed incomplete are history and current research. with the current research information you uploaded, can you add a bit more text just to summarize what the study found out? There's a picture there with some description but it would be good if you can put into dot points what the significant findings are.

It would also be good if you can write something on the visual cortex of the brain. I think it links in with the section on Optic nerve. Maybe mention some of the genes related to the various stages of eye development. It doesn't have to be a lot of detail - just suggest what stage of development the genes are responsible for.

It would be good if you used more research papers instead of using the textbooks. If you are using the textbooks, it's good to track down the references the textbook used. This means you can put the relevant research papers as reference instead.

--[[User:Z3332863|Z3332863]] 16:08, 23 September 2012 (EST)

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- the opening is very catchy with the diagram

- good brief introduction although it might help to give a brief description of the different parts.

- Since you have no other tables maybe put the history section in the table so it breaks up the text.

- It might be better to make the images a little bigger so we can see the labels. Also with the images for ‘formation of primary optic vesicles’ you might want to fix the way it’s laid out on the page --- may be put it in a table with a description of what each labelled part contributes to. Also there is no description bellow the pictures either. All the pictures in the development area looks very clustered so break it up with text.

-Large section of the optic nerve development ad retina development seems to have no references. But a lot of good detail is present which shows that you have researched. Although try to use articles rather than books.

- The student drawn images have tiny labels so fix that up maybe and also add copyright information.

- Fig 4 and 5’s formatting should be fixed so they are either side to side or broken up by text. Same goes with fig 6 and 7 – needs copyright info.

- In the current research section a detail of what the research is about and how it is helpful can be given.

- Try using less websites and more journal articles.

- Sections of ciliary body, iris and lens development could use some more detail. The section on iris has the development time in months…it will be beneficial if you kept it in weeks to be consistent with the rest of the parts. The section on lens, aqueous chamber and cornea doesn’t have any development time associated with it which might be useful too.

- I’m aware that you cant do abnormal section in detail but you can still mention some abnormalities in a section without going into heavy detail.

Overall it is a good page but formatting of the pictures and their placement has to be fixed. Some more text should be added to the development section of iris, lens, eyelids etc.

--[[User:Z3333794|Z3333794]] 09:18, 23 September 2012 (EST)

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Firstly, the picture at the top immediately shows us the topic you are discussing: vision. This is good, but you might want to decrease the size slightly by stating the number of pixels in your file description. Your introduction includes the anatomy of the eye, which you should probably put under a separate heading. Expand the introduction a little and tell us what you will be presenting on your site.

The history is quite short – aim for more significant dates and discoveries and try to put them in an organised table. Within your history section you have images relating to development of the optic vesicle and lens. It seems like these should be incorporated in your next section on development. Good images though, but this time increase the size so the reader doesn’t have to open every single one of them to read the labels.

It seems like most work has gone into the section of development, which is good because we are focussing on the development of vision! The content relates really well and shows research has been done. There are a few sentences that strongly suggest they have been researched, however they are not references. This is in particular for the optic nerve and retina sections. Again, make sure the labels on the images can be read without having to open the file. You may also want to put the images together (optic nerve section) so the reader can easily see the changes happening during development. It is really good that you refer to the images within your text. The second half of your development section could do with a few images to complement the text. I personally think you should expand upon the lens development, because this is an important structure of the eye. What happens after migration into the embryo? If you find some related molecular information, eg. essential transcription factors, you could provide a brief explanation of these too and the role they play in vision development.

You started on your current research and a few references are present, as well as an image. I do not know what this image is and there is pretty much no text explaining any research that is currently undertaken. Please expand upon this!
The links should probably be listed under the heading ‘external links’ and as you expand upon certain sections, please keep adding to the glossary. For instance, I could not find the term ‘neuroblastic layer’ in the glossary (from the retina section).

With all of your images: please provide a title, description, source, copyright information, student image template. Some of your references will also need to be changed to avoid errors, citation of webpages and doubling-up of references. See the ‘editing basics’ on the embryology website.

Hope this helps!
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In regards to the information presented (outcomes 1 and 9), as the project is still in progress it is understandable that some areas are incomplete. There is so far good, concise information on the structure of the development of the eye and the structures involved in vision. It would be useful to include information on the genetic factors involved in vision development as well as have a section explaining the processes involved with vision. Also, for the Current Research section (outcome 5), it would be better to explain the aims and findings of the research papers cited rather than just referencing the papers and images without describing their significance to research progress. In terms of peer teaching (outcome 4), the page contains a good balance between technical terms and simple language for understanding on the development of structures for vision; additionally, the inclusion Glossary helps to clarify any technical terms.

The most striking part of the layout (outcome 2) is the use of images to demonstrate the development of structures involved in vision. This is great because it makes the page interesting and provides a visual understanding on the development of the eye. However, at times the images could be better placed: for example, in the introduction the pictures appear stacked on top of one another. Additionally, the images in the introduction show similar structures, so perhaps select only one to better aid the flow and appearance of the page. Throughout the page, the images utilised could be provided with more description and linked to the text in order to improve flow and enhance written explanation. Perhaps some information, such as the timeline, could be sorted into a table to improve the layout.

In regards to outcome 3, some of the information provided (e.g. in the section on Development) is not referenced. Additionally, some of the references in the Reference list need to be formatted correctly with author, date, title of the page, publisher (if required) and any other necessary information. It would be useful to follow the style of the automatic default referencing.

Hope the feedback helps and all the best with your project!

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Group Assessment Criteria:
# ''The key points relating to the topic that your group was allocated are clearly described'' The introduction explains why the eye is important and lists the anatomical structures, however there is no indication that this project page is about the development of the eye!
# ''The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area''. The project predominantly focuses on the development of the eye, and goes into detail the development of each individual structure. There are also a lot of student-drawn images and diagrams of developmental stages which shows a good understanding of the topic area.
# ''Content is correctly cited and referenced''. There is no copyright notices for any of the images and they all lack explanations.
# ''The wiki has an element of teaching at a peer level using the student’s own innovative diagrams, tables or figures and/or using interesting examples or explanations''. The text is easy to understand and there are many student-drawn diagrams, which makes the content more interesting to read.
# ''Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities''. I would say the information provided satisfies the aims of the project, however the research does not go ‘beyond the formal teaching activities’ as it lacks additional information such as abnormalities, normal functioning etc.
# ''Relates the topics and content of the Wiki entry to learning aims of embryology.'' The contents and topics are strongly related to the learning aims of embryology.
# ''The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic and covered the key areas necessary to inform your peers in their learning.'' All the content provided is well researched and relevant to the aims of the project. They key areas are well described.

Additional points:
* I feel that this page would benefit from a timeline or ‘weekly development’ table that briefly describes what structures are developed in each week. This would provide a good summary of the content as well as allow reader to be able to understand how the development of each structure relates to each other.
* Good referencing of images throughout project page – relating images to content
* Less paragraphs, more tables, bullet points, emphasize certain important points
* History & research sections look incomplete.

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Vision development review:

The key points are Cleary described and Topics have been divided in an efficient way allowing maximum information and an extensive insight into each of these segments, although at this stage there is not enough detail for each.
There is a substantial amount of visual stimulus although the quality of these stimuli is questionable. For example the images under the heading “research history” lack proper sized labelling, an individual must click on the each image in order to appreciate it. The initial image needs to decrease in size dramatically as is overwhelming and takes away from the product
Proper citation is evident however; there is a minority of untidy citations along with no copy write information for a certain image. Significant, deep research is not evident, I believe more research is required; there is a respectable attempt to relate content to learning aims of embryology. Information in the history section is insufficient and perhaps needs to be expanded upon.
To improve more information on each topic is required, review of visual displays (mainly balancing images between sections some have plenty where as other lack) and copy write information is essential

--[[User:Z3330795|Z3330795]] 10:20, 24 September 2012 (EST)
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The layout of the page is relatively good. If anything it appears little too image heavy at the moment. On the note of images, the referencing is good but don't forget to include the student template note with each image. The inclusion of some student drawn images in great to see but it might be an idea to make the labels larger as they are hard to read. The use of subheadings is great, a really logically well set out page. The references need a bit of work, some are spread sporadically throughout the page and some in the references section just list the URL along with the error on reference number 13.

The introductory is brief but alright. However the first two images are largely similar, not sure why both need to be included. Perhaps if possible it would be nice to link each of the main anatomical bullet points you have listed in your introduction to their associated developmental paragraph further down the page.

The History of development is coming along nicely but perhaps would be easier to read if it was in the format of a table. Also the Atlas of the Development of Man needs to be properly referenced with the author in the reference section. It would be nice to have some information relating to the pictures uploaded in this section.

The section on Development is well done and it is interesting to look at the individual development of each structure. It might be an idea to include some more references to when each structural development occurs. Current Research really needs some more content. The glossary is a nice addition and helpful.
Hope this helps

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The top image of the eyes is a great idea to introduce an audience to your topic. The copyright of the image is there along with the reference. However, the hand drawn image do not have a reference as to where you located the information for the diagram. The images further down the page which are referenced to a textbook had no copyright associated with it. It is important to make sure that the textbook is not protected by copyright laws before placing those images in your page. Referencing and copyright needs to be included in every image on the page, many of your images don't have the necessary information.

The information is easy to understand, however it is difficult to locate. Things seems to be out of place. Try not to include images on both side of the page, it is highly distracting as they alternate far too often. I also noticed that development and function were both under one heading. This made things a little confusing as the information between the two topics were shared in the same paragraph.

What I found to stand out were the historic images. These are a great addition to the page. Having said that, they're often difficult to understand and therefore explaining the images would be great. The history, current research and glossary sections all seem to be incomplete, these need to be worked on.

Something that i found to be really well explained was the developmental stages of the eye and associated structures. This is very important as the topic is about the development. Although the information for this section seems to be great, there seems to be a lack of references, it is important to cite where you derived the information from.

Overall the page seems to have the right information, however, just remember to include the right references, make your diagrams and labels more visible and try to organise your information into tables or dot points to make it easier to follow.

Hope this information helps

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There is a good balance of images and text throughout the page. Prior to final assessment the page outline and formatting of image and text positioning is required. The first image at the top the page, requires correct referencing and acknowledgement that it has been uploaded as part of a student assignment. This is also required for the image titled “Eyediagramcolour1”.

Since the previous lab, held in week 9, it is positive to see that the group has altered some of the uploaded image information, with particular reference to the self-drawn/uploaded images.

The area of the page which shows that there is a “useful links” heading and an external link within the current research section, should be placed or moved into the external links section at the bottom of the page with the appropriate information that Dr. Hill has required for placing external links on a page. Also, the references within the ‘current research’ section may also need to be apart of the reference list.

I found this page visually appealing and I liked that this group have included an image gallery section. The use of the external links were appropriate to the topic and that the extent of the glossary for now is good, however, by the final evaluation would potentially need to be larger. Finally found that the headings for each segment of the broader topic were well positioned and relevant.

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'''Vision'''

Overall the detail within Group 1's page is very informative and very well set out, having each individual part of the eye named with information about the development of that certain feature is great. The information about the iris, cornea, choroid and sclera, eyelids and lacrimal glands were undeveloped compared to that of the retina and optic nerve. Even though the retina and optic nerve are the sensory receptors, the other components of the eye should have an equal amount of information about the development because without these parts the sensory part would not function at its best.

I would recommend having developmental pictures that you have placed at the beginning of the page places around the block of writing in the iris, lens, and chamber area just to break up the text and to show the development of each part in stages. The History section, as they stated has more to come, and I hope there is more to come for the current research as well as both sections need more information.
I feel that the images, while being hand drawn, were not sufficient enough to communicate the full detail of the developmental process and there were not enough references to validate the statements that were made throughout the page.
Overall however it was a very well written project with a well thought out progression from introduction to finish.

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The introduction is good, I like the use of images to help describe your topic. The images you have for your page are great. They complement the information you have on your page however the historical images at the top of the page feel like they are added because they are images, they should have a small description and be numbered if you like to show the order they go in. As is stands at the moment I found them to be confusion and just a space filler.

Under the current research heading, I think you guys would benefit from giving a brief overview of what the research is not just listing the articles.

If possible you should add a part about the first person/s to discover the mechanisms of eye development. You should also add a small part about the genetic parts which cause these mechanisms.
--[[User:Z3220343|Z3220343]] 21:28, 25 September 2012 (EST)

== Group discussion ==

Have you guys looked at some sources about the development of vision in embryos?
Do you have any idea how you want to divide up the topics we can work on?
--[[User:Z3370664|Z3370664]] 13:31, 21 August 2012 (EST)

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Hey everyone, I haven't looked at anything yet, sorry! Hopefully end of this week/start of next I'll start adding things. Ben --[[User:Z3373894|Z3373894]] 19:33, 21 August 2012 (EST)

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Heya. Thinking that we should do a time line rather than dividing up the different structures of the eye. Em --[[User:Z3254758|Z3254758]] 10:40, 22 August 2012 (EST)

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I looked through all the embryology textbooks I have (the two prescribed texts, as well as another book) and they all divide up the eyes into different parts and talks about how each of the parts develop, rather than a timeline. So i was thinking, maybe we could focus more on describing how each of the different parts of the eye develop, and then we could do a timelime briefly at the end? (By the way, you're not supposed to mention your name) --[[User:Z3370664|Z3370664]] 10:21, 29 August 2012 (EST)

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Sounds good. I have put a few suggestions for the different parts of the eye on the page. We need code-names if you don't want to put your name so that we know who is saying what.
Please don't put any information on the actual page without referencing it.--[[User:Z3254758|Z3254758]] 10:45, 29 August 2012 (EST)

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We also can't use content from Dr Hill's pages. The photos that are on our page are great, but we will have to replace them. We also desperately need to divide the sections between us. Maybe 2 people do 5 eye structures each, one person does intro and history, and another does current research and useful links? --[[User:Z3254758|Z3254758]] 11:45, 29 August 2012 (EST)

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The textbooks are going to be really useful, I'd say divide it up the way the textbook does it. Sorry guys, didn't realise we can't use Mark's stuff. Will look for similar images later -.- --[[User:Z3373894|Z3373894]] 11:51, 29 August 2012 (EST)

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Also I'm happy to do 5 eye structures :) I think. --[[User:Z3373894|Z3373894]] 11:56, 29 August 2012 (EST)

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Okay guys, I'm doing retina and optic nerve, lens, eyelids, choroid and sclera. Em (z3254758) is doing the other structures (we can reassign if either of us find a structure that is excessively complicated). That leaves intro/history and current research/useful links. '''Also!!!''' I have to do a marine science camp in the mid sem break and so won't be available to make contributions. Sorry but I'll keep adding as soon as uni goes back. --[[User:Z3373894|Z3373894]] 12:13, 29 August 2012 (EST)

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Awesome, no worries. Thanks for your contribution so far, let me know if we need to redistribute. Enjoy your camp! --[[User:Z3254758|Z3254758]] 16:08, 29 August 2012 (EST)

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Hey guys I'm really sorry for the late notice but I've dropped this Embryology course. Tried logging on a few days ago to let you know what was going on but the server wouldn't connect. So sorry to stuff you all around. Goodluck with everything. Emma --[[User:Z3330686|Z3330686]] 10:55, 5 September 2012 (EST)

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So does this mean we only have 3 people in our group now?

Anyway, I'm sorry i haven't contributed yet. I had been looking up articles and reading them to help you with the structures, but haven't written up notes yet, as I have so many other assignments to do that are all due soon. I am happy to do intro/history and current research/useful links. And after i do those parts, I can help you guys with the structures if there are any structures you're stuck with. I can help look for images too. I'll also do a brief timeline/overview of eye development after you guys finish the structures. I'll post up the links to the articles I found that you might find useful for the structures. --[[User:Z3370664|Z3370664]] 12:22, 10 September 2012 (EST)

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Oh my goodness the more I research the more confused I get! I keep finding conflicting information- hence why some things are in capitals and italics and why I haven't put references for everything. Am hoping you guys can shed some light? For the iris I had one resource that said two completely opposite things about what it develops from :S :S :S

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Yeah I know, I've had similar problems of conflicting sources :( I'm mostly relying on the online textbooks because surely they can't be wrong? And all the papers have a large emphasis on the genetics and it's hard to find a simple anatomical description. We can come back later and fix anything that's unresolved. --[[User:Z3373894|Z3373894]] 14:35, 17 September 2012 (EST)

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P.S. nice eye collage at the top whoever posted it. Adds a nice human touch. It's really cool to look at! :)

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yay I'm glad you like it! :)
This is the problem, I was confused about the conflicting statements so I went to a textbook and that was what said the two different things... in the specific section it said one thing and then in the summary it said the opposite o_O trying a few other textbooks at the moment. Ya am very sick of reading about genetics.--[[User:Z3254758|Z3254758]] 21:49, 17 September 2012 (EST)

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Hey i found a good article which i think you might find useful. It also has nice images. I want to email them and ask permission to use their images in our project.

To read the article, Log into the UNSW library and search 'Eye development' by Jochen Graw

Current Topics in Developmental Biology, 2010, Vol.90, pp.343-386

--[[User:Z3370664|Z3370664]] 23:49, 17 September 2012 (EST)

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Well peer review is tomorrow and the page is still somewhat lacking haha... It would be good to get something under the headings "research history" and "current research" even if it's only a few sentences so the space isn't completely blank. I'll try and add a few more things to my sections tomorrow morning. I had a quick look at the Jochen Graw article and it has good summaries of genetic stuff as well. Once I get all the anatomical stuff down on my sections I'll come back and add genetic stuff at the end if I get time. --[[User:Z3373894|Z3373894]] 17:16, 18 September 2012 (EST)

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Hey guys, I went through the page and fixed some formatting issues with the images. Also went through my images and added descriptions, copyright and the "student template" thing - don't forget to do that to all the images you upload. I also took some of the advice in the comments and enlarged my labels and added an orientation to my images. Don't forget that according to the course timetable that this project is due at the end of the lab next week!!! That's '''Wednesday 3rd October.''' So keep adding stuff!!! --[[User:Z3373894|Z3373894]] 17:15, 25 September 2012 (EST)

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Okay I also just went through and fixed up the references we have so far, so instead of having the same reference come up multiple times in the reference list it just comes up once. Here's the help page that tells you how to do it: http://embryology.med.unsw.edu.au/embryology/index.php?title=Help:Reference_Tutorial#Multiple_Instances_on_Page

I think we should try and get content from all of the potential papers you guys posted below on this page so we get a nice, well rounded reference list. We've already referenced the textbooks several times (I am mostly guilty of this - sorry), so let's try and reference the same info in papers instead. Also try and get the reference info right the first time - it takes ages to go back and do it!!! --[[User:Z3373894|Z3373894]] 18:16, 25 September 2012 (EST)

----

Hey is there a way to make the citations appear automatically in the references, or do i have to add them individually/manually?

I'm still working on my parts and will add more stuff this week. I'm sorry i had so many assignments due recently. Now that i have them out of the way i'm working on this assignment now.

--[[User:Z3370664|Z3370664]] 10:53, 26 September 2012 (EST)

==Potential Resources==

<pubmed>16959249</pubmed>
<pubmed>11687490</pubmed>
<pubmed>22219630</pubmed>
<pubmed>19449303</pubmed>
<pubmed>11069887</pubmed>
<pubmed>12223402</pubmed>
<pubmed>9043062</pubmed>
<pubmed>15558474</pubmed>
<pubmed>15558475</pubmed>
<pubmed>9609835</pubmed>

--[[User:Z3254758|Z3254758]] 17:58, 4 September 2012 (EST)

----

Lhx2 links the intrinsic and extrinsic factors that control optic cup formation:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2778739/?tool=pmcentrez

Innervation of the Mouse Cornea during Development:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3053279/?tool=pmcentrez

Fibromodulin Regulates Collagen Fibrillogenesis During Peripheral Corneal Development:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2965449/?tool=pmcentrez

Development of extraocular muscles require early signals from periocular neural crest and the developing eye:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3248700/?tool=pmcentrez

Eye Morphogenesis and Patterning of the Optic Vesicle:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2958684/?tool=pmcentrez

Targeted deletion of Dicer disrupts lens morphogenesis, corneal epithelium stratification, and whole eye development:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2787093/?tool=pmcentrez

Anterior eye development and ocular mesenchyme:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2094210/?tool=pmcentrez

--[[User:Z3370664|Z3370664]] 12:31, 10 September 2012 (EST)

User:Z3254758

2012-09-26T01:44:20Z

Z3254758: /* Peer Review */

==Lab Attendance==

--[[User:Z3254758|Z3254758]] 10:04, 25 July 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:35, 1 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:09, 8 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:04, 15 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:15, 22 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:05, 29 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 11:08, 12 September 2012 (EST) arrived at 10:10am

--[[User:Z3254758|Z3254758]] 10:02, 19 September 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:07, 26 September 2012 (EST)

Ciliary Body
Iris
Cornea
Aqueous Chambers
Lacrimal Glands
Extraocular muscles

==Lab 1==

<pubmed>22178154</pubmed>

This article reviews some important features of capacitation as well as presenting their findings regarding the role of PLD-dependent actin polymerization in sperm motility during capacitation. They demonstrated the importance of PLD-dependent actin polymerization for developing hyper-activated motility.

==Lab 2==

{|
|-
|'''Task 1'''

|-
|[[File:Paternal_chromatin_mouse_embryos.jpg|thumb|left]]

|-
|'''Task 2'''

|-
|Rac1 and RhoA are Rho GTPases that regulate the invasion of the human embryo through the endometrial stroma. Inhibition of Rac1 expression prevents embryo invasion of the stroma, whereas inhibition of RhoA promotes it. Rac1 also plays a role in human endometrial stromal cell migration.

<pubmed>PMC2562412</pubmed>
|}

==Lab 3==

1. Gestational age refers to the time period between the first day of the mothers last period and birth. Fertilisation age is the time between conception and birth. <ref><pubmed>15520122</pubmed></ref>.

==Lab 4==

1.

Amniocentesis- involves using a needle to take a sample of amnitoic fluid. It can be used to detect down syndrome and turner syndrome among other abnormalities.

Chorionic villus sampling- a needle is used to take a sample of chorionic villus (placental tissue). It is helpful in detecting down syndrome and cystic fibrosis.

2.

<pubmed>3240835</pubmed>

This paper demonstrates the successful use of intrathecally injected mesenchymal cells derived from human umbilical cord blood to partially recanalise a dissected basilar artery. The patient was a 17 year old Korean man with infarction of the bilateral pons, midbrain and right superior cerebellum as a result of the basilar artery dissection.

The paper identifies that human umbilical cord blood contains hematopoietic stem cells, as well as mesenchymal stem cells which express neural makers Tuj1, TrkA, glial fibrillary acidic protein and cyclic nucleotide phosphodiesterases.

As a result of his condition the patient became quadriplegic, was unable to speak, and was unable to move his eyes, as well as a number of other symptoms. His clinical symptoms were visibly improved 5 days after the initial treatment with the mesenchymal cells. After the 27th day of treatment he regained his gag reflex, was able to swallow, had pupil dilation and was able to move his eyes, his soft palate stopped sagging, and the rigidity of his muscle tone reduced enough to allow him to sit in a wheelchair.

==Lab 7==

1.Provide a one sentence definition of a muscle satellite cell (b) In one paragraph, briefly discuss two examples of when satellite cells are activated ?

Satelite cells are stem cells that are located under the basal laminar of each muscle. When muscle is damaged satelite cells infiltrate the muscle and repair or replace it. They are normally quiescent.

2.In one brief paragraph, describe what happens to skeletal muscle fibre type and size when the innervating motor nerve sustains long term damage such as in spinal cord injury?

==Lab 8- Peer Review==

'''Group 2- Somatosensory'''

-Great introduction. Really puts the project in context and justifies the importance of your research. Citations need to be formatted like the rest of the page

-History of discoveries-very poor syntax, word repetition and no paragraphs. What is Weber's full name? This is entitled "history of discoveries" when it is actually just a very brief, nonspecific summary of "Weber". What about the other interesting discoveries from various scientists over decades?

-Adult Central Somatosensory systems- ascending in what? Position? Importance? Activity? Sensitivity? This needs a more informative opening sentence.

-Trigeminal system and Development of the Primary Somatosensory Cortex- are well explained and ideas are presented in a logical, flowing manner. Great picture with a good description and referencing (impressed you drew it).

-"making connections between...." what do the stages mean? Why does it start at stage 23 instead of stage 1?

-touch/touch receptors is good but where are the references?

-pain and pressure sections also good but needs paragraphs and the formatting of citations is incorrect

-bullet points in pressure section need a brief sentence introducing their purpose. Papers listed at bottom of section should be correctly cited instead of having hyperlinks

-interesting info in temperature

-current research- maybe you could put the name of the paper and authors and explain how they conducted their study? That would help with understanding the nice picture

-Glossary is incomplete

-Needs more pictures

-minor grammatical and spelling errors throughout but overall very good and well sequenced.

'''Group 3- Taste'''

Overall this is an excellent project. Well written, great informative photos, good use of tables, and comprehensive information that's well explained.

A few of the photos don't have the appropriate copyright information and some sections of text haven't been referenced, but in general this ticks all of the boxes

'''Group 4- olfaction'''

-numerous typos and syntax errors throughout. My favourite is "naval cavity"

-generally well explained and I like how you've used different formats for each section to keep it interesting

-this seems a bit random-

"SINUSES: A:
EFFECT OF AMNIOTIC FLUID ON THE DEVELOPMENT OF OLFACTION IN THE FETUS (current research in the field):"

-I think the anatomy section should come before the developmental timeline just to put the developmental stages in context

-abnormal function is very comprehensive :)

-current research is great, it appears some quality research went into this

-excellent use of resources throughout, including your external links. I think you've covered everything well

'''Group 5- abnormal vision'''

-content of introduction is good and immediately puts the page in context. Emphasises abnormal development. Perhaps reconsider the syntax of some of the sentences

-paragraphing throughout project needs review

-a picture near the beginning would make the page more engaging. Seeing you can't talk too much about normal eye development, it might help in conveying some information

-you frequently make use of the carnergie stages, which is great, but perhaps briefly describe what this system means

-it's good that you have contrasted normal and abnormal development for each structure, but make sure the information isn't repeated in the "normal development" section, or perhaps remove that section altogether

- info about what the different genes control is good. What does "the first embryonic days 8.5" mean?

-I assume the two separate sections in "ocular manifestations" are genetic and environmental, but because they're not stated in the intro of this section and there's so much information in-between, it's difficult to tell. The formatting of this section adds to the confusion. Keeping the information and formatting consistent for each abnormality will make this easier to follow. The appropriate heading, sub-heading etc formatting needs to be used as well

-I like your case study, it reminds us of how these problems effect real people

-no current research or external links section?

-excellent use of resources

'''Group 6-Hearing'''

-you had me at puppy

-good intro (a few typos) and history (I like your table)

-the start of adult anatomy and histology should have an opening sentence instead of just listing information. There is no histology?

-I'm guessing the heading for development is meant to be bigger instead of it appearing to be part of "adult anatomy and histology"? This section is very comprehensive!

-your "neural domain" drawing is a good way of explaining this concept

-the summary box is a great idea, but perhaps it should be entitled "Summary of inner ear development"

-I don't understand why this is present- "NOTE: DEFINITIONS OF SYNDROMIC AND NON SYNDROMIC HEARING LOSS". You have explained what non-syndromic hearing loss is in the 1 Mutation of GJB2 gene section, but as your note says, it might be good to have a brief section with these definitions

-your genetic and structural disease tables are nice but I feel that the formatting should be the same for all of the diseases, or you should explain why you've chosen to emphasise these abnormalities

-the PDF in the Toxoplasmosis section seems to have some good info, but should be formatted like the other references

-the references in the rubella, cytomegalovirus infection, drugs and technologies to detect sections need to be formatted properly. Some info in drugs section isn't referenced at all

-technologies to detect is not a very informative heading, you need to specify what you're detecting. The syntax in this section and "technologies to overcome the problems" is poor (including the headings)

-in text hyperlinks in current research section are good for making page more interactive

-you appear to have used a lot of great resources

== References ==
<references/>

2012 Group Project 1

2012-09-26T01:01:45Z

Z3254758: /* Ciliary Body */

User:Z3254758

2012-09-26T00:07:19Z

Z3254758: /* Lab Attendance */

==Lab Attendance==

--[[User:Z3254758|Z3254758]] 10:04, 25 July 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:35, 1 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:09, 8 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:04, 15 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:15, 22 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:05, 29 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 11:08, 12 September 2012 (EST) arrived at 10:10am

--[[User:Z3254758|Z3254758]] 10:02, 19 September 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:07, 26 September 2012 (EST)

Ciliary Body
Iris
Cornea
Aqueous Chambers
Lacrimal Glands
Extraocular muscles

==Lab 1==

<pubmed>22178154</pubmed>

This article reviews some important features of capacitation as well as presenting their findings regarding the role of PLD-dependent actin polymerization in sperm motility during capacitation. They demonstrated the importance of PLD-dependent actin polymerization for developing hyper-activated motility.

==Lab 2==

{|
|-
|'''Task 1'''

|-
|[[File:Paternal_chromatin_mouse_embryos.jpg|thumb|left]]

|-
|'''Task 2'''

|-
|Rac1 and RhoA are Rho GTPases that regulate the invasion of the human embryo through the endometrial stroma. Inhibition of Rac1 expression prevents embryo invasion of the stroma, whereas inhibition of RhoA promotes it. Rac1 also plays a role in human endometrial stromal cell migration.

<pubmed>PMC2562412</pubmed>
|}

==Lab 3==

1. Gestational age refers to the time period between the first day of the mothers last period and birth. Fertilisation age is the time between conception and birth. <ref><pubmed>15520122</pubmed></ref>.

==Lab 4==

1.

Amniocentesis- involves using a needle to take a sample of amnitoic fluid. It can be used to detect down syndrome and turner syndrome among other abnormalities.

Chorionic villus sampling- a needle is used to take a sample of chorionic villus (placental tissue). It is helpful in detecting down syndrome and cystic fibrosis.

2.

<pubmed>3240835</pubmed>

This paper demonstrates the successful use of intrathecally injected mesenchymal cells derived from human umbilical cord blood to partially recanalise a dissected basilar artery. The patient was a 17 year old Korean man with infarction of the bilateral pons, midbrain and right superior cerebellum as a result of the basilar artery dissection.

The paper identifies that human umbilical cord blood contains hematopoietic stem cells, as well as mesenchymal stem cells which express neural makers Tuj1, TrkA, glial fibrillary acidic protein and cyclic nucleotide phosphodiesterases.

As a result of his condition the patient became quadriplegic, was unable to speak, and was unable to move his eyes, as well as a number of other symptoms. His clinical symptoms were visibly improved 5 days after the initial treatment with the mesenchymal cells. After the 27th day of treatment he regained his gag reflex, was able to swallow, had pupil dilation and was able to move his eyes, his soft palate stopped sagging, and the rigidity of his muscle tone reduced enough to allow him to sit in a wheelchair.

==Lab 7==

1.Provide a one sentence definition of a muscle satellite cell (b) In one paragraph, briefly discuss two examples of when satellite cells are activated ?

Satelite cells are stem cells that are located under the basal laminar of each muscle. When muscle is damaged satelite cells infiltrate the muscle and repair or replace it. They are normally quiescent.

2.In one brief paragraph, describe what happens to skeletal muscle fibre type and size when the innervating motor nerve sustains long term damage such as in spinal cord injury?

==Peer Review==

'''Group 2- Somatosensory'''

-Great introduction. Really puts the project in context and justifies the importance of your research. Citations need to be formatted like the rest of the page

-History of discoveries-very poor syntax, word repetition and no paragraphs. What is Weber's full name? This is entitled "history of discoveries" when it is actually just a very brief, nonspecific summary of "Weber". What about the other interesting discoveries from various scientists over decades?

-Adult Central Somatosensory systems- ascending in what? Position? Importance? Activity? Sensitivity? This needs a more informative opening sentence.

-Trigeminal system and Development of the Primary Somatosensory Cortex- are well explained and ideas are presented in a logical, flowing manner. Great picture with a good description and referencing (impressed you drew it).

-"making connections between...." what do the stages mean? Why does it start at stage 23 instead of stage 1?

-touch/touch receptors is good but where are the references?

-pain and pressure sections also good but needs paragraphs and the formatting of citations is incorrect

-bullet points in pressure section need a brief sentence introducing their purpose. Papers listed at bottom of section should be correctly cited instead of having hyperlinks

-interesting info in temperature

-current research- maybe you could put the name of the paper and authors and explain how they conducted their study? That would help with understanding the nice picture

-Glossary is incomplete

-Needs more pictures

-minor grammatical and spelling errors throughout but overall very good and well sequenced.

'''Group 3- Taste'''

Overall this is an excellent project. Well written, great informative photos, good use of tables, and comprehensive information that's well explained.

A few of the photos don't have the appropriate copyright information and some sections of text haven't been referenced, but in general this ticks all of the boxes

'''Group 4- olfaction'''

-numerous typos and syntax errors throughout. My favourite is "naval cavity"

-generally well explained and I like how you've used different formats for each section to keep it interesting

-this seems a bit random-

"SINUSES: A:
EFFECT OF AMNIOTIC FLUID ON THE DEVELOPMENT OF OLFACTION IN THE FETUS (current research in the field):"

-I think the anatomy section should come before the developmental timeline just to put the developmental stages in context

-abnormal function is very comprehensive :)

-current research is great, it appears some quality research went into this

-excellent use of resources throughout, including your external links. I think you've covered everything well

'''Group 5- abnormal vision'''

-content of introduction is good and immediately puts the page in context. Emphasises abnormal development. Perhaps reconsider the syntax of some of the sentences

-paragraphing throughout project needs review

-a picture near the beginning would make the page more engaging. Seeing you can't talk too much about normal eye development, it might help in conveying some information

-you frequently make use of the carnergie stages, which is great, but perhaps briefly describe what this system means

-it's good that you have contrasted normal and abnormal development for each structure, but make sure the information isn't repeated in the "normal development" section, or perhaps remove that section altogether

- info about what the different genes control is good. What does "the first embryonic days 8.5" mean?

-I assume the two separate sections in "ocular manifestations" are genetic and environmental, but because they're not stated in the intro of this section and there's so much information in-between, it's difficult to tell. The formatting of this section adds to the confusion. Keeping the information and formatting consistent for each abnormality will make this easier to follow. The appropriate heading, sub-heading etc formatting needs to be used as well

-I like your case study, it reminds us of how these problems effect real people

-no current research or external links section?

-excellent use of resources

'''Group 6-Hearing'''

-you had me at puppy

-good intro (a few typos) and history (I like your table)

-the start of adult anatomy and histology should have an opening sentence instead of just listing information. There is no histology?

-I'm guessing the heading for development is meant to be bigger instead of it appearing to be part of "adult anatomy and histology"? This section is very comprehensive!

-your "neural domain" drawing is a good way of explaining this concept

-the summary box is a great idea, but perhaps it should be entitled "Summary of inner ear development"

-I don't understand why this is present- "NOTE: DEFINITIONS OF SYNDROMIC AND NON SYNDROMIC HEARING LOSS". You have explained what non-syndromic hearing loss is in the 1 Mutation of GJB2 gene section, but as your note says, it might be good to have a brief section with these definitions

-your genetic and structural disease tables are nice but I feel that the formatting should be the same for all of the diseases, or you should explain why you've chosen to emphasise these abnormalities

-the PDF in the Toxoplasmosis section seems to have some good info, but should be formatted like the other references

-the references in the rubella, cytomegalovirus infection, drugs and technologies to detect sections need to be formatted properly. Some info in drugs section isn't referenced at all

-technologies to detect is not a very informative heading, you need to specify what you're detecting. The syntax in this section and "technologies to overcome the problems" is poor (including the headings)

-in text hyperlinks in current research section are good for making page more interactive

-you appear to have used a lot of great resources

== References ==
<references/>

Talk:2012 Group Project 5

2012-09-25T23:21:37Z

Z3254758: /* Group evaluation */

{{2012GroupDiscussion}}

==Group evaluation==

The text on this page is very good, detailed and to the point. However a lot more images are needed on the page to make it more appealing, interesting and easier to follow.

The section under Ocular Manifestations is a little difficult to keep track of, there needs to be more of an introduction in that section highlighting the two sections that are to be discussed, then there should be a clear division between the two.

Also the placement of the few images on the page need to be organised a little better. The referencing on this page is done very well and its good to see an extensive use of resources.

I really liked the way how sub-divided the different abnormalities in vision and matched them with the corresponding image. However, further headings would be better for finding specific abnormalities especially when it comes to genetic causes. Also, the addition of normal eye functioning summary is a good recap on the eye before getting to abnormalities.

The molecular pathways are a bit hard to follow and confusing, although interesting.

The images are great and balanced with text, but the set out needs to change to make it more “friendly looking”.

Your glossary is good but may need a few more additions and extensive references are excellent.

Summary: overall very good and not complaints besides maybe think about the setting of the text to pictures.

Good luck with the rest ☺

----

- A very good start to the page with the introduction. It gives an overview of the page and is very nicely done --- an image in the beginning will make it more effective. Right now the starting is very text heavy so an image will not just tone it down but will have a more profound impact.

- Normal eye development is good too but just to make the text look not so heavy you can consider putting it in a table like a brief summary.

- Traditionally research timeline should go on the top of the page but I don’t think it’s a big issue. Again you should consider tabulating it so it looks not so text heavy.

- I like how you talk about each part of the eye and different genes. You have a range of articles which also seems great and shows how much effort you have put in.

- Research section is not so extensive so far so you might want to work on that.

At the moment the organisation of the page is not great and it is very text heavy. Even though there are many images on the page it still looks very text heavy. Adding tables might help breaking that up and also add make the page look bright.

-------------

The information that is present on this page is fantastic. However, i think the layout of the page inhibits your ability to access that information a little bit. Large sections of information go unbroken by images/tables/diagrams. This strains the eyes a little bit, making it a bit of a chore to read the page. Try and include a few more images, even if they are basic. In other areas however, the images included break up the page too much, creating large white areas, detracting from the pages presentation.

There also seems to be disunity in how the different sections are formatted in regards to paragraph headings and lists. This may just be a product of teamwork and assigning different people different sections to do.

However, one important thing is that I cannot fault you for the information. It seems to be in depth, up to date, and with well structured referencing. The images you have included are well explained and referenced as well.

Overall, quite good :)

-------------

As shown by your choice of sub-headings and research, the key points of your area of research are being addressed well! Your introduction flows well and gives a great overview of your page to the readers.
Due to the focus of your page being on abnormal vision, a more succinct effort should be made to introducing normal eye development. I suggest the use of a student made flow diagram in order to clearly present the information as well as satisfy the criteria of this task.

The approach to the abnormalities section is so far on a great track. I particularly like the separation between genetic and environmental abnormalities as well as the use of a lot of research to introduce interesting concepts and clarify the reader’s understanding. In saying this, it would be beneficial to organise images in this section in a consistent manner, to mimic the image ‘appearance of cornea due to CHED’.

Be sure not to include too much detail on the molecular pathways and proteins if not entirely necessary in informing the audience about the abnormality in development. This would help eliminate any concepts that are too complex to understand.

The placement of the timeline before the new research was a good idea as it gives the reader good background knowledge. I would consider condensing this into a table so that it is more easy to read.

Overall, a great page but it could be more easier to read if the information was organised in a more succinct manner such as in tables, dot points and flow charts. The referencing style is consistent and correct and there is a good balance between old and current research.

-------

"The introduction is good in the manner that it provides some brief background information regarding the normal development of the eye and abnormalities. Additionally, I liked how the introduction described the aims of the page because it sets up a structure for the reader to follow. Just make sure to proof read this section: “The development of the eye is very sensitive and REQUIRES accurate...”

In regards to the information presented and layout (outcomes 1, 2, 4 and 9):

1. Normal Eye Development: This section appears very well researched. I like how you referred to the stages throughout development. However, this section could be enhanced by adding an image of the normal eye structure and development – this acts as a reference point for your page viewers, allowing for a clear visual comparison between the abnormalities and normal structure.

2. Abnormal Development: I like the overview provided at the beginning as it sets the scene for what points you will be covering in this section. Great job. All sections are quite good, just perhaps include more images to further enhance your page.

a. Abnormal lens development: I liked how you first described the function of the gene in development and then stated any abnormalities that arise when the gene is not expressed or mutated. I liked how you included an image for the crystalline genes; just make sure to refer to the image in text (e.g. see fig. 1. or see accompanying image).

b. Abnormal corneal development: Similar to the abnormal lens section, there is a good explanation provided for each gene involved. Just some improvements: make sure to reference all information; e.g. No reference provided for “The ion transporter SLC4A11 promote sodium-dependent transport of borate as well as flux of sodium and hydroxyl ions. It has been shown that SLC4A11 is expressed in the endothelial cells of the cornea, and mutation of....”. The accompanying image has been referenced correctly and described, good work!

c. Abnormal retinal development: Once again, a great scope of research and information and suitable image. I liked how you described the impact of each mutation explicitly such as in Albinism “ganglion cells of retina decreased by 25%”. This really helps the reader to understand the extent of the abnormalities from certain gene mutations.

3. Ocular manifestations: the opening sentence is slightly vague. Could you please state which two separate sections that you are referring to? The section that follows could be better organised. It seems to jump from genetic issues to a research timeline then to future research on that disease to another example of a genetic mutation which produces abnormalities. I would suggest putting the research timeline shortly after the introduction and integrating research history not just on LCA but other abnormalities as well. However, the content for all these sections is well referenced and interesting to read. The balance between text and images between LCA and anopthalmia/micropthalmia sections is good and are both really interesting to read! I liked how you provided some epidemiological data and clinical manifestations in depth accompanied by suitable images. However, the environmental abnormalities section could use with more dot-point styles and images to enhance the presentation and aid in your descriptions.

In regards to peer teaching (outcome 5), this page was an absolute joy to read and all technical language was explained in the glossary. Just make sure to pay attention to those minor improvements. Good job!"

------

Introduction gives an overview of your project. This gives structure to your project. The introduction is a little too brief. It would be nice to add some detail about the significance of eye abnormalities:
* how important is vision to humans
* how does vision abnormalities affect people
* how many people are suffering from major eye abnormalities, etc.

Great images. They highlight the severity of abnormalities associated with vision. It would be nice if you can make the images a little bigger or add more images. it just seem there's too much text and not enough images to break it up.

The normal development section is succinct and give sufficient background information so readers can understand the abnormalities section. It would be good if you can put this normal function part into point form or table. for example, 'stage...development'

The gene mutations section is very complicated. Maybe talk about the FOX genes and Pax6 genes in abnormal lens development and not as a separate section. This is so readers can associate the mutation with the disease immediately, without having to scroll to the bottom to find the consequences of such mutation. The layout makes the disease and gene section hard to understand. Maybe set it out as:
* Genetic mutation
* diseases from this mutation
* clinical symptoms of diseases
* treatments for the diseases

Most of the images are well referenced, except Albino Fundus image. for this image, you need the PMID reference style.

References 45-48 should be placed as one reference.

--[[User:Z3332863|Z3332863]] 17:26, 23 September 2012 (EST)

----

Your introduction is quite short, but it does state what you will be discussing on your page. You might want to include the normal development in the introduction, to allow for an overview of what normally happens before you actually start on the abnormal development. It just seems a little odd that you have abnormal vision as you title and then almost immediately after that you have a normal eye development heading.

I really like the chronological order used in the normal development section. It might be a bit easier to read if you use dot points. References seems to be fine, however, 4 and 5 are the same. It might also be useful to create a link to the group page on normal vision development.

Abnormal development consists of a few subheadings. Personally, I would delete the lines below the different subheadings. It will make it look more like one section on abnormal development. I think it was a good idea to look at the different parts of the eye related to abnormalities – lens, cornea, retina, etc. You look at different genes which play an important role at a certain developmental stage and you explain the resulting effects. I can see a lot of research has been done on this section. Images will need to be made bigger. They look insignificant with this size and it just seems like the text is going on and on. A lot of terms mentioned in this section are not included in the glossary, eg. Dysgenesis, substantia propria, CRX (what does it stand for?). Please add these in. Again, check your references, because some are the same, eg. 8 & 9.

Ocular manifestation is part of the abnormal development section (I think), so please make sure you show this with the headings. Again, immediately below this seems to be another heading with genetics, which has nothing included… or does LCA belong to genetics? I am a bit confused due to all your different headings and lines which seem to separate parts that may potentially belong together.

In your LCA section I would change the order of text a little: definition (as you have at the start), then epidemiology (which you have at the bottom), then the section on Dr Leber (up to “…placing great emphasis upon the high incidence of hereditary factors.”), lastly a new paragraph on the diagnosis (“As stated in the section on… diagnostic protocol for LCA”). The link to Abnormal Retinal Development does not work and will need editing. I can see that your timeline refers to LCA in particular and it is quite expansive. The one reference provided leads to a website with a timeline that seems to have been copied and pasted into your project. Please change this into your own words and (where possible) provide references to the original papers. The table also seems to be located in a strange position and it may be better to include this information in a table on history (in general), which you do not have at the moment. New research development also focuses on LCA only. Maybe create a separate section at the end where you can mention this and include more current research in brief paragraphs. The image relates well and has the appropriate citation, copyright and student template. The description could include a little more information.

Anophthalmia and microphthalmia are other genetic abnormalities described. Again, with the image you can expand slightly upon the description, but besides that it relates well to your text. Information provided is good, and includes the clinical description, genetic causes and management. Most important is that you use the same layout for your headings throughout your project. Within this one section you are using different subheadings and it all looks a bit chaotic and makes it less encouraging to read. You explain the role various genes play and I would like to know at what week/gestational stage they are important and can cause these abnormalities. Make sure all your references are correct, eg. There is no reference for 30.

It is probably good you only focused on 2 abnormalities caused by environmental factors. Images could really complement the text (although your whole page could probably use a few more images), so please add these. You include some relevant information and statistics, but make sure you also keep adding to the glossary. References are also the same for 45-48, hence these need editing.

In my opinion, firstly change the layout of your page and make it more organised with logical headings. Then focus on some of the other things mentioned above.

Hope this helps!
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Your introduction is relatively well written and the brief explanation of new terms such as microphthalmia was particularly useful. Perhaps it would be possible to break the text into two paragraphs to make reading easier.

It is really good to see a section included about normal eye development as it provides a basis of understanding for the remainder of the page. Concise and to the point and not too complex, it's great. Only suggestion would be to place it in a table perhaps with each Carnegie stage a new entry.

Layout of abnormalities is very logical covering the main areas of developmental abnormalities. However it is slightly confusing that immediately under the title Abnormal Lens Development more information on normal development is given. Allocating the defects to their associated individual genes is good but perhaps instead of a dotpoint a subheading would be of more use. The actual information is clearly and effectively written. The inclusion of the pictures clearly illustrates the abnormalities but their placement is a little odd. Perhaps they are too large. The captions on the pictures are appropriate and the pictures are appropriately referenced and it is great that the link to the picture contains more information.

Under the title "Ocular Manifestations" perhaps indicate what the two sections are, just so the following on sections make sense and don't appear disjointed. The sections on the genetic caused abnormalities is fascinating and very well written. The timeline included in the information about Leber Congenital Amaurosis is particularly interesting. The spacing in the section on genes associated with Anophthalmia and Microphthalmia appears slightly strange. The figures included are particularly illustrative and appropriate. Similarly the section on environmentally caused abnormalities is really well written and interesting.

Perhaps a more extensive section on current research could be included. If possible, link the words in the glossary to where they appeared in the text. This is the coding if you don't have it [[#Glossary|'''Words for Glossary''']]. Just add that in place of the word when you first mention it in the text. The citing and referencing is really well done. It also shows a great depth of research. The figures/photographs so far included are brilliant but the inclusion of a student drawn diagram somewhere if possible would be effective. Also try and fix the general layout of the project, possibly including some more subheadings. In general the content relates to the the course and is pitched at an appropriate level. Hope this helps.

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The introduction was okay, however avoid referring to the rest of the page within the introduction - it should stand on its own.

Normal eye development is very succinct, however maybe consider adding an image here to aid with your explanation.

The abnormal section is very good and well researched. The images included are good, however as with the introduction, avoid using language such as "in the section below, we have focused on..."

The ocular manifestations section is very good but just needs to be organised better, the headings are somewhat confusing. Good use of images, timeline, and subheadings for different genes. The management section is also very interesting and can be elaborated on.

The glossary is good but the formatting can be improved - perhaps putting the key terms in bold or at least making all the terms italic rather than half and half.

The reference list is extensive which is good, but don't forget to add to the external links section.

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The differentiation between genetic and environmental abnormalities is an excellent idea and stood out immediately. This differentiation adds on to the organisation of the page and allows the information to be read with ease. However, the inclusion of tables and flow chart would go well in the page and make the information easier to follow. In addition to this, it would be great to see a few external links to make the page more engaging and guide audience to more more detailed information about certain abnormalities.

The information included is very extensive and highlight a great level of research. However, some of the information seems to be quite complex and difficult to understand. It is fine to cover difficult to concepts, but try to expand on it to allow for people to understand it or provide external/internal links which would provide more information and make the content easier to comprehend.

Having explained the function of genes in development and then explained any possible abnormalities that can arise in abnormal lens/corneal/retinal development made the information much easier to grasp. It allowed the information to flow and and the text seemed to follow a logical order. The inclusion of images in this section is great, whereas more images/diagrams is required for the rest of the page.

Covering the normal development is important and the chronological order used makes it easy to follow, however, keep in mind that there is a different project solely on normal development and therefore try not to expand to much about this topic. The referencing seems to be correct, and it is great to see a large range of sources have been used. One section that will require some work is the current research section as it does not seem like there is enough information. Apart from the issues raised, this page seems very promising.

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*'''Introduction:''' The introduction is quite well written and very detailed. Rather than going straight into details of development, perhaps first make it clear from the exactly what this project page is about and what content you will be covering. There are also some grammatical errors, such as “treatments or cures ‘’’maybe’’’ developed in the future and these conditions can be better managed.” Maybe = may be
* '''Normal eye development:''' This section shows a good depth of research, is strongly related to the aims of the embryology course and shows a good depth of research. Improvements could be made by the use of bullet points, tables or bold text to highlight key points. Also, labeled images or hand-drawn diagrams would go well to compliment the text.
* '''Abnormal Development:''' There is a good depth of research and it is well written. The use of headings, figures and italics makes it easy to follow the flow of information. Improvements could be made by providing more information about the diseases, for example, what is Peters' anomaly (Corneal Opacity) and aniridia (lack of Iris)? Is it curable? What are methods of detection? How will it effect the future baby?
*'''Ocular Manifestations:''' This section seems incomplete; or maybe its just poorly organized? What are the two separate sections? Is this related to the sections that follow?
* '''Research Time line:''' This is a good time line, however only one source has been used. This provides a good summary of significant discoveries, but it has not been explained why these discoveries were important or how it is relevant to the development of the eye.
* '''New Research Development:''' This section is well researched, however the poor structuring and layout of the information makes it difficult to read and follow. For example there are many headings and subheadings however it is unclear what sections of information are grouped together. The images draw the readers attention and there seems to be a good depth of research into the topic.
*'''Group Assessment Criteria:''' The key points relating to the topic that your group was allocated are clearly described in the introduction. The choice of content and depth of research shows a good understanding of the topic area, however the information could be better organized by the use of tables, bullet points and bolded text to highlight key points. The content is correctly cited and referenced. Most sections are well paraphrased for teaching at a peer level, however the use of hand-drawn diagrams and/or labeled images could enhance the information in the text. The information covered is strongly related the the learning aims of embryology.

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It was very good to see that this interesting topic has been well researched and that there are a number of references appropriately cited in the page.

Currently, there is a lot of text that, I as a reader, felt overwhelmed when assessing. More/larger images may need to be uploaded, or the correct formatting/resizing of existing images in order to potential rectify these concerns. It is noteworthy, however, that the ratio between text and imaging improves toward the bottom end of the page.
It was good to see that there was all relevant summary, referencing and uploading information for the images that were present. Keep in mind that there is an option, and we have been encouraged to upload images that have been student drawn.

The over all formatting of the page, besides being packed with written information, had a couple of spacing issues, from extreme spaces between the bullet point genes and consequent descriptions, in the ‘abnormal lens development section’, to virtually no singular spacing between the research timeline. in the ‘Genes’ section.

A way to aid to the above so that the page potentially is more visually appealing, is to place the genes and subsequent function into tables, or even placing the timeline information in a table form, or adding originality by actually placing this information on a timeline generated by one of the group members.
Overall though, I found that it was a very engaging topic and page presented.

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Group 5- abnormal vision

-content of introduction is good and immediately puts the page in context. Emphasises abnormal development. Perhaps reconsider the syntax of some of the sentences

-paragraphing throughout project needs review

-a picture near the beginning would make the page more engaging. Seeing you can't talk too much about normal eye development, it might help in conveying some information

-you frequently make use of the carnergie stages, which is great, but perhaps briefly describe what this system means

-it's good that you have contrasted normal and abnormal development for each structure, but make sure the information isn't repeated in the "normal development" section, or perhaps remove that section altogether

- info about what the different genes control is good. What does "the first embryonic days 8.5" mean?

-I assume the two separate sections in "ocular manifestations" are genetic and environmental, but because they're not stated in the intro of this section and there's so much information in-between, it's difficult to tell. The formatting of this section adds to the confusion. Keeping the information and formatting consistent for each abnormality will make this easier to follow. The appropriate heading, sub-heading etc formatting needs to be used as well

-I like your case study, it reminds us of how these problems effect real people

-no current research or external links section?

-excellent use of resources

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==Discussion==

Hey so what organ did everyone decide on heart or liver.
I vote for the Liver

Hi Team! I would first like to apologize for not coming on Wednesday on our practical. So I am sorry one more time for that. I am coming to practicals this Wednesday so we can discuss our topics. Just to ask what happen on Wednesday in regards of our group project? So we need to decide between heart or liver to write our project? If that is so...I vote for the heart then:)

'''remember to sign after contributions to this page'''

Hey kidlings, just to let you know, I'm going to be looking through my path/grey's anatomy textbooks for anything i can possibly find.
I think we should start with a little intro of what is the normal development and then have some abnormalities that can stem from that?
Thoughts?
--[[User:Z3374173|Z3374173]] 19:17, 21 August 2012 (EST)

Hey Team, some ideas for the focus of our topic. 1. a basic overview of the development of the eye, 2. divide the eye up into it regions of development and look at the abnormalities that can occur, including the factors which make it abnormal: congenital or defect; percentage of occurance in society and/or likely hood aquiring it; processes of the abnormal development (how abnormaility occurs); living with the abnormality; any treatments and/or prevntions for the abnormality.
--[[User:Z3220343|Z3220343]] 19:31, 21 August 2012 (EST)

Possible sources: [http://www.sciencedirect.com/science/article/pii/B9780750673365500098]
[http://www.sciencedirect.com/science/article/pii/B978032302394800019X]
--[[User:Z3374173|Z3374173]] 10:12, 22 August 2012 (EST)

Textbook: The Developing Human Chapter 20 [http://www.mdconsult.com/books/page.do?eid=4-u1.0-B978-1-4377-2002-0..00020-5--s0015&isbn=978-1-4377-2002-0&uniqId=352694541-2#4-u1.0-B978-1-4377-2002-0..00020-5--s0015] --[[User:Z3220343|Z3220343]] 10:14, 22 August 2012 (EST)

Looking through textbooks, I have found Retinoblastoma which is a tumor usually in the posterior retina. It says it can occur in 2 year olds but also can occur at birth, so that could be a developmental one. I found that in my pathology textbook, Others i found could be Horner's syndrome, that apparently can start developing in fetal development. I'll go through my mums old midwifery textbooks too. Anyone else find anything?--[[User:Z3374173|Z3374173]] 16:49, 26 August 2012 (EST)

Hey so i was looking through the textbook and i found a list of defects of the retina. further down it also talks about congenital glaucoma. [http://www.mdconsult.com.wwwproxy0.library.unsw.edu.au/books/page.do?eid=4-u1.0-B978-1-4377-2002-0..00018-7&isbn=978-1-4377-2002-0&uniqId=355501465-2#4-u1.0-B978-1-4377-2002-0..00018-7--s0015]
i found this while surfing pubmed may be of some use?[http://www.ncbi.nlm.nih.gov/pubmed/20933211]
i had heard of a genetic disorder in which if both parents are carriers the baby has 25% chance being born blind. i think this was the disorder if not, it still could be interesting for our assignment [http://www.blindness.org/index.php?view=article&catid=38%3Aother-retinal-diseases&id=253%3Aleber-congenital-amaurosis&option=com_content&Itemid=88][http://www.ncbi.nlm.nih.gov/pubmed/22842231][http://www.ncbi.nlm.nih.gov/pubmed/22842230]--[[User:Z3220343|Z3220343]] 21:09, 28 August 2012 (EST)

I think I shall do Horner's Syndrome. [http://jtcs.ctsnetjournals.org/cgi/content/full/120/2/419]--[[User:Z3374173|Z3374173]] 11:29, 29 August 2012 (EST)

Hi team :D I just found an article that talks about all the current knowledge on conditions related to abnormal visual development in infants. In the article, they have aslo included prevalence, risk factors and mechanisms that are involved with the development of these conditions. I think it would be quite useful to our own topic. Just letting everyone know, i will be doing congenital cataracts. [http://www.ncbi.nlm.nih.gov/pubmed/21478704]--[[User:Z3331330|Z3331330]] 12:36, 29 August 2012 (EST)

Heres another article description of the normal visual development, each component of the visual system is included and explained very clearly, this would be useful for our general overview on the development of the eye. In particular, the retina development is also mentioned in the article which we can make use of when comparing our disorder with the normal development. [http://www.wonderbabiesco.org/UserFiles/File/Graven%20and%20Browne%20Visual%20Dev%2008.pdf]--[[User:Z3331330|Z3331330]] 12:47, 29 August 2012 (EST)

Hey Guys, After trawlling through stacks of info on Horner's syndrome I'm not satisfied with the amount of info there is so I'm going to change it up and try Chorioretinal Scars. I can find more information and really hope this comes together!! --[[User:Z3374173|Z3374173]] 21:34, 10 September 2012 (EST)

I did the normal development, feel free to check it over, make changes etc, I have the PDF files of the articles i used if you need to check. Also, I've forgotten how to make all the reference bind together if they are the same text, i cant seem to find the help to help me so I'm just going to leave it until someone can help me!
--[[User:Z3374173|Z3374173]] 17:07, 12 September 2012 (EST)

hey team, do u guys think that we have enough information? what else should we add in if we do need some more.--[[User:Z3331330|Z3331330]] 22:00, 17 September 2012 (EST)

Talk:2012 Group Project 4

2012-09-25T23:20:44Z

Z3254758: /* Group evaluation */

{{2012GroupDiscussion}}

--[[User:Z8600021|Mark Hill]] 09:59, 18 September 2012 (EST) This is a recent review on smell. http://jcb.rupress.org/content/191/3/443.full JCB content allows reuse.

Not for reuse but good reading - [http://www.ncbi.nlm.nih.gov/books/NBK55980 The Neurobiology of Olfaction]

==Group evaluation==
The work needs to be spell checked before you submit it, make sure you get all your grammar right as well. I think you should add more to your introduction, and make it a little simpler, easier to follow. Also throughout your project you tend to use a lot of long paragraphs, especially in the current research section.

Though the developmental timeline that is set up is very detailed, it can be a bit hard to follow and a little confusing. There is too much text and no pictures at all to help demonstrate what is being said about the development. The ratio of images to text in the anatomy and abnormalities sections however is very good and makes it more interesting to read.

It’s good to see that you have some external links put up on the page and also that you’ve used quite a few references to do your research rather than just a few.

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WOW! I really can’t come up with anything bad to say about this wiki.
Text and image are nicely balanced.
Developmental timeline was very easy to follow and succinct which is always nice.
It was good to have research images alongside hand drawn images.
Diagnosis and treatment sections may need some expantion.
List of references current and varied – always good to see.

All in all this was a very good project and congrats of the good work. Keep it up.

Good luck with the rest ☺

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- The introduction is very good and brief --- although it does not tell the reader that it is about development of olfactory sense.

- The history section is immaculately done --- You have used a couple different sources and gone into enough detail about each historic background which tells me that you have thoroughly research this part.

- The development section is also very nicely done --- I like the layout of this section. Also the sentences are very clear and structure is easy to follow. There is a large section in week 6 which does not have any reference so you might want to fix that up. Same goes for week 7 abd week 8.

- When you start talking about anosmia it just abruptly follows normal function so you might want to add the heading “abnormal development”. It might even be a good idea to put normal function before normal development to put things in prespective.

- In Kallmann’s syndrome although it was very interesting to read, it is very heavy on genes which you have not addressed in the normal section portion. I do realise for some of them you have put a description as to what they do in normal development but see if you can integrate it with normal development too.

- It is also good to see that you have a diagnosis section and a treatment section too. It was very informative.

- Current research is well put together

Overall your project is looking pretty good….Just some minor formatting issues. The text is a little on the heavy side so some images especially in the development section will be good.

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The introduction was very interesting to read - 1000 genes related to olfactory system is amazing. The introduction isn't too long which is great. However, it would be good to include in text citations. Where did you get your information from?

The history section will look better if it was put into a table.

The 'Timeline of Development process' is excellent because it clearly presents so much information with respect to the time the differentiations took place. I can't wait to see the images though because some of the concepts were hard to understand without visual aids. For example, 'specialized areas in rostrolateral regions of head of olfactory placodes' - where is that on the embryo?

The normal function section was short. This is nice to see because this project is about development, not about the function. It would be good to include a diagram of the signaling pathway in this section, just to make it interesting.

The structure section needs a bit more information. Maybe put the olfactory bulb image in this section as it relates more to structure. You can also put some images of the cribiform plate in here too.

Abnormality section on Kallmann's syndrome was very well written. It had lots of detail, presented clearly in point form. Can you describe some of the other diseases in just as much detail as well? It just seems like Kallmann's syndrome is the main disease and there's not a lot of focus in other abnormalities.

In current research, 'the 'role of Odorant receptors' need to have some text and content in that section, not just the reference.

--[[User:Z3332863|Z3332863]] 16:58, 23 September 2012 (EST)

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Page is well structured. Tables and images break up the information nicely. Some of the images lack an in depth explanation of what they depict/represent when you click on them. I know for some of the images it might be hard, but i think it would make for a more thorough way of presenting the information.
Not to much a critique, but you spend a large amount of time and space on the abnormalities section. When combined with the current research section and the images, only about a third of your page is information on olfaction. An even less of it is on the actual embryology when considering the timeline of discoveries and introduction. Try and draw out the embryology section a little further, considering the context of the website and who would be visiting it.

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Your introduction is good and gives a brief overview of what the olfactory system entails. There were a few spelling mistakes, which can easily be corrected. Make sure you do tell the reader what you will be discussing on your page – development of the olfactory system and the particular subheadings you will focus on. The image could do with a few more labels for orientation, but besides that it complements the text and contains the correct citation, student template, etc.

The history section is good and quite extensively researched. Most groups will provide the history in a table, with dates in chronological order (to clearly show history and developing knowledge over time). This might be something to think about. I would suggest a ‘date – description – significant person’ type of format for a table. Good image, but it is displayed next to Pearson instead of Kollman. It is also difficult to see what it is and read the labels without opening the larger version, so you might want to increase its size slightly. Because this is a student image I would like to see the original – if possible provide a link to the Atlas of the Development of Man 2.
You should also explain what Kallmann’s Syndrome actually is, because this seems a little vague.

Your timeline of developmental process looks amazing and is enjoyable to read. Some of your words are printed in bold and link to the glossary. In one of your next sections the words link directly to the glossary, so you should probably do he same thing here. I really hope you can add pictures to this table to complement your text! Not quite sure what the line at the bottom (SINUSES:A:…) is doing there… either delete or expand upon this.

Structure: you only have a link here. Please provide text and image to explain the structure briefly. The YouTube link should be there to help the reader understand this section, instead of being the only thing this section is made up of. The video is not your own work, so please add your own work to this!

The normal function section was alright. It has some useful information in there, however, only a single reference listed at the end. It seemed like more references should be included within the paragraph. I would also include the fact that depolarization is an all-or-nothing response. The threshold needs to be reached for depolarization to occur, but there is no build-up over time to reach this threshold. It has to happen at that one instance. The links should be listed under the heading ‘external links’ or, if used as references, incorporated as proper references within the text. The olfactory bulb image is a little small and the description is quite brief. Though, good citation of the source and a student template is present.
I think the olfactory bulb image and the epithelium image should be included in the ‘structure’ section.

The abnormality section includes Kallmann’s syndrome and a quick definition has finally been provided! Please include this in the history section too. This section was a joy to read! Very interesting! A lot of effort has been put into the research and references have been done very well. I assume OB stands for olfactory bulb – please indicate this in the text. The dotpoints listed in the ‘clinical features’ section could do with a brief explanations instead of me having to scroll up and down between the text and the glossary. The image is excellent and shows a good simplified concept of what happens. Good descriptions, source citations, etc are added too. It was good to see diagnosis and treatment included.

Current research starts with a link, which seems quite random – include this in the external links section. You found some interesting and current research. References are only listed at the end of each paragraph, but should probably be included within as well. The image relates to one of the projects and descriptions are appropriate. Nothing has been added to the ‘role of odorant receptors’ though (apart from a reference). Please add a brief paragraph to this section.

Terms should be added to the glossary. The reference list also needs checking, because some are the same (eg. 11 & 12) and others do not have a reference (eg. 7 & 17).

Hope this helps!
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The introduction is quite small but very precise, indicating the function and the components of the olfactory system but maybe include one or two sentences in the introduction telling readers that it is actually about the development of the olfactory system, not just the function and components of it. After all, introduction is meant to show others what your project is about. The hand-drawn image there is very nice but maybe more information need to be provided other than just labelling parts of it. Along with the image, there are the important informations such as the copyright notice which is good to see.

The history of discoveries section is very well-researched but it will be easier to read if it was in a table. The timeline, i thought was very good because there are a lot of useful information about the development of olfaction which relates to the research topic. The developmental process is explained in quite simple terms but i notice some of the scientific terms in the timeline are not explained in the glossary, this makes it a little bit hard to understand the whole process. It is very interesting that a youtube link has been included in the structure section, this is really a good peer teaching but make sure you referenced the video correctly to avoid plagiarism. The section on Kallman's syndrome is quite interesting but the structure of that section is a bit messy, maybe try clarifying and tidy it up a lit. But i can see that a lot of research effort has been put into it which is good and the variety of resources used in the section is very broad. More images should be put here because right now, there is just a huge block of text in the section. Images will balance out the heavy text load and attract readers more.

The current research section contains a lot of useful information and it relates to the research topic well. Again, images should be put here because right now, there are just small blocks of text in the section without any images, this maybe a little bit boring for readers.

Overall, the project looks well-researched and relates pretty well to the research topic. The balance of the images and text still needs to be fixed but in terms of the text and information on the page, i think it is pretty sufficient and in-depth especially the timeline of development and current research section. There are some terms in the glossary which is good but maybe more terms should be added. The structure of the page is good, very easy to follow. There are a few external links which is always good to put there for anyone that are interested by the topic and want some further information about it. Referencing is good, there is only one minor citing error (no.7), but it should be easy to fix. Hope this helps :)

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The introduction provides a good overview to the topic and the associated images have all the appropriate referencing information.

The history section is interesting and well researched with good use of subheadings.

The timeline of development is very useful and informative however is quite text-heavy, some diagrams may be able to help here.

The anatomy and normal function sections don't add very much to the page, especially in terms of embryological development. Adding more to these sections may help.

The abnormalities section is good, with a lot of information on Kallmann's syndrome, however other abnormalities (if there are any?) could be included to expand this section.

The current research section contains a lot of information in a small amount of space. It is quite jargon-heavy although this might not be able to be avoided. The subheadings are good as they act to split this section into discrete units.

The glossary and external links are very good, and the references are extensive which is good.

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* '''Introduction''': The information is very interesting and provides a good overview of the olfactory system. The only improvement that could be made is clearly stating what content is going to be covered on this project page. Also, “The olfactory system are often ‘’’divide’’’ into a peripheral mechanism”
* '''History of Discovery''': This sections presents a good summary of each research paper, detailing a background of the researchers and the importance of each discovery. Well done!
* '''Time line of developmental process''': This section shows a good depth of research and provides detailed descriptions of each stage of development. However, the information provided is quite complicated and would not be easily understood by peers. This could be overcome by the use of labeled diagrams or hand drawn images, which I can see is yet to come. Overall this is a well done section, the colors draw the readers attention and I like the use of bolded text to highlight important information.
* '''Anatomy of the Olfactory System & Normal Function''': This provides a good amount of information seeing as the focus of the page is about olfactory development, not the function & final structure. The only improvement could be providing an explanation in the figure provided.
* '''Congenital Abnormalities''': This section is well organized and includes all relevant content. Very interesting to read.
* '''Current Research''': A well researched section and coverage of content. Each paper is summarized and the importance of each discovery is made clear. It would be nice to include a direct link to each article.

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For me this is one of the best projects of the 6 groups. It is extremely well researched, as seen through the extensive reference list. It is evident that the group has gone above and beyond, researching even more than required for the topic, or standards set by other groups, such as clinical approaches, and much information on current research.

I found that the formatting in the upper part of the page, specifically the section under the title ‘normal function’ was a bit awkward in relation to text and image positioning. It felt that it was not consistent with the flow of the rest of the page.
Also the first table may require an in-filled colour or even lines (can be a light or pale colour), just so each column and the single uploaded image is more defined and linked to the correct year/individual.

The ‘Choanal Atresia’ tomography image requires acknowledgement that the image was uploaded as part of a university assessment. However, really appreciated the breakdown of where the arrows were pointing and the relevance in relation to your specific topic.
Images for the tables need to be finalized and uploaded; ensuring that there is appropriate referencing, whether they are student drawn, or sourced from the literature.
Found that the student drawn diagrams were really detailed and easy to understand and appreciate. Each was also relevant to the topics, which they were linked/associated to.

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The introduction while small gives a great overview on what olfactory is. You could add a small overview on what the page is about to make this part a little longer.

I like your table on development however there is some information in the table which is missing references, you should see to that soon and add a reference. Some images in this section would be nice and if there are not going in the table then you might want to delete the image column.

The anatomy of the olfactory system is quite small; this part could possibly be added to your introduction.
Kallmann’s syndrome is done very well and is quite thorough and as a result the choanal atresia section looks lacking. I would suggest adding this to the bottom of your abnormalities section and if no more information is going to be added to the page maybe state that other abnormalities include - choranal atresia and then maybe an external link.

Current research section is quite detailed and I would not add anything else to this section. I did notice that Role of Odorant Receptors is just stated with a reference and no information. If nothing is to be added here I would just delete this heading.
--[[User:Z3220343|Z3220343]] 21:33, 25 September 2012 (EST)

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Group 4- olfaction

-numerous typos and syntax errors throughout. My favourite is "naval cavity"

-generally well explained and I like how you've used different formats for each section to keep it interesting

-this seems a bit random-

"SINUSES: A: EFFECT OF AMNIOTIC FLUID ON THE DEVELOPMENT OF OLFACTION IN THE FETUS (current research in the field):"

-I think the anatomy section should come before the developmental timeline just to put the developmental stages in context

-abnormal function is very comprehensive :)

-current research is great, it appears some quality research went into this

-excellent use of resources throughout, including your external links. I think you've covered everything well

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== External Links ==

Hey team... make sure you check the links i added to the external link section. They are great resources to use in your sections.

[[User:Z3333427|Z3333427]] 10:19, 21 August 2012 (EST)

== Group Topic Selection ==

So we have a choice between:

stem cells

Neuronal development

Sensory development

I personally don't have a particular preference but I think neural or sensory would be something different to touch on since there's still so much progressing research in the field.

'''Hey all :-). Thanks for getting the ball rolling. I like the latter two options, in particular neuronal development - from there we can pick a certain aspect and explore not only normal development but perhaps research complications and genes/factors implicated when things go wrong.
p.s. It would be great if we could figure out a regular time to meet during the week outside the lab so we can properly discuss and share our research'''

Just a heads up- Mark preferred that we don't put our names up anywhere on the wikipage for privacy purposes!

'''sensory system'''
hello everyone, it seems like the options we had chosen for sensory were picked before we had a chance and therefore I have asked Dr Hill for us to do the "hearing" system. I don't mind changing if the group chooses to do so, however, I thought it would be a good idea to have a topic locked in. Please let me know if you want to do a different topic

--[[User:Z3333427|Z3333427]] 11:32, 14 August 2012 (EST)

=Designation of parts=

There must be an addition of current research and technologies in each area

Make sure this is not presented as an essay (balance text and writing with images, tables etc)

Possibly a history of the development of understanding

[[User:Z3331264|Z3331264]] 11:54, 15 August 2012 (EST) Timeline and processes of development

--[[User:Z3374215|Z3374215]] 11:59, 15 August 2012 (EST)I would like to do a history section and the introduction

Please identify which part you want to be responsible for, keep in mind that you can work at any topic you would like.

Introduction: Andrew

History: Libby

Abnormalities: Stephanie

Future research: Libby (future research on normal function) Stephanie (future research on abnormalities/treatments)

Timeline: [[User:Z3331264|Z3331264]] 20:18, 22 August 2012 (EST)

==Progress of individual tasks and project queries==

[[User:Z3331264|Z3331264]] 20:18, 22 August 2012 (EST): I will be creating a table to indicate the timeline of development of olfaction during embryonic development. I will make changes to the initial table as I go along so as to avoid not contributing any online material until the end.

--[[User:Z3333427|Z3333427]] 00:58, 25 August 2012 (EST)The table is a really good idea, we should probably have at least another one as information becomes much more organised. Just to let you know that I changed it to Carnegie stages as most sources organise their information based on those stages, and keep in mind that the placodes dont form until week 11 or 12, so there is no need to have stages 1-10.

--[[User:Z3374215|Z3374215]] 17:52, 27 August 2012 (EST) I've got some information on historical developments but information is really difficult to find. I've made some progress but not sure how much more there is that I can do. In light of that I might also take a look at the subheading "Structure". It's referring to the physical structure of the developing olfactory system?

--[[User:Z3331264|Z3331264]] 19:33, 27 August 2012 (EST) Carnegie stages are a good idea! I also think its important to include a brief description of the development of the anatomy of the nose (turbinates etc) as well as a bit about the brain development in the locations of the olfactory nerve. Don't freak out when you read my additions, I do my research gradually, which means I will first add what I found in the textbook and then later on fill in the gaps plus add a research dimension with current lit.

--[[User:Z3333038|Z3333038]] 10:09, 29 August 2012 (EST) Hi all, you heard it from Mark today but just restating, even when doing draft work you must reference properly as you go along or you will be penalised.

--[[User:Z3331264|Z3331264]] 11:22, 29 August 2012 (EST) Decided to just stick to weeks rather than carnegie stages because sometimes between carnegies stages, little events occur which will make the table larger and more confusing!

--[[User:Z3333038|Z3333038]] 18:01, 29 August 2012 (EST) Hey Libby, I found a review article which contains a brief history on olfaction abnormalities in development in the introduction: http://www.springerlink.com.wwwproxy0.library.unsw.edu.au/content/288u546105v08575/fulltext.pdf

--[[User:Z3333038|Z3333038]] 19:26, 29 August 2012 (EST) Hi all, just letting you know im working through pathophysiology for Kallmann's syndrome on a word document at the moment and will post some as I go online to document progress. Currently working on a diagram demonstrating the abnormalities in the olfactory bulb neuronal connections.

--[[User:Z3333038|Z3333038]] 21:18, 30 August 2012 (EST) Completed my diagram and have uploaded it with referencing. I based my diagram on an image from a review article which I have referenced - have emailed Dr. Hill to check that all is alright in terms of copyright.

--[[User:Z3331264|Z3331264]] 22:25, 4 September 2012 (EST) : Hey everyone, this is the html code to add to your parts whenever you wish to place a link of a word to the glossary:

[[#Glossary |'''put the word you want linked to glossary here''']]

--[[User:Z3374215|Z3374215]] 17:18, 5 September 2012 (EST) Hi Stephanie, I found an interesting article about abnormal development of the olfaction bulb of mice when exposed to alcohol. Don't know if you'd seen it. http://www.ncbi.nlm.nih.gov/pubmed/21736737

I also read that article! Pretty interesting stuff

[[User:Z3333427|Z3333427]] 17:48, 7 September 2012 (EST) That is a good idea, please email Dr. Hill if you are unsure about anything as huge penalties apply for ignoring copyright. By the way our group project is looking good, more diagrams and tables similar to the one we have now would be great.

--[[User:Z3333038|Z3333038]] 08:21, 11 September 2012 (EST) Thanks for the article :-). I will add it to a section on congenital anosmia. I emailed him and he said it was absolutely fine, as long as I referenced my source information.

--[[User:Z3374215|Z3374215]] 12:00, 12 September 2012 (EST) Just a note to myself more than anything. I need to reference Julius Kollmann's textbook in the history section and add a diagram.

--[[User:Z3333038|Z3333038]] 20:12, 14 September 2012 (EST) Loving the page team! The drawings are great! Nearly finished my bit, just have to add a brief paragraph for the other congenital abnormalities and one more research article.

--[[User:Z3333038|Z3333038]] 22:35, 14 September 2012 (EST)Hey Libby I found this website for timeline/history: http://www.medlink.com/medlinkcontent.asp...it talks about discoveries of congenital olfactory defects.
--[[User:Z3333038|Z3333038]] 09:15, 15 September 2012 (EST)Completed abnormalities and submitted 3 current research articles. Happy to take on extra parts.

--[[User:Z3374215|Z3374215]] 12:06, 15 September 2012 (EST) Thanks Stephanie that site looks great! I'll check it out soon.

--[[User:Z3333038|Z3333038]] 11:06, 19 September 2012 (EST) Important! Hey guys, we really need to work on the development of each structure and the genes involved. Who can help me out?

--[[User:Z3333038|Z3333038]] 11:47, 19 September 2012 (EST)Note to self: Make section on external links.

--[[User:Z3331264|Z3331264]] 17:49, 20 September 2012 (EST) The table that I included walks through the timeline of development. I have slowly been adding more and more research including genes involved in patterning. But at the same time, I don't want to dive into too much information in order to maintain the balance between text and images. I have figured out a way to do this without making it all seem too simple, so just bear with me for the next week and you'll see it tie in well. Cheers

--[[User:Z3333038|Z3333038]] 09:52, 25 September 2012 (EST) I have stumbled across an extra abnormality - although it is more a structural defect rather than a sensory defect, it still relates to olfaction so I have added it in. Will keep it brief though as whilst it is a common nasal abnormality, it is not so much a sensory one. Also, Z3374215 and I are concerned - are you two alright with your parts? We know, like the rest of us you have other assessments but it's been a long while since we've seen any major contribution - if you're stuck we are happy to give you a hand.

--[[User:Z3374215|Z3374215]] 19:07, 25 September 2012 (EST) Hi guys, don't want to impinge on anyone elses work but I think I have to change a couple of generic features on the page. If you don't mind I'll just stick the external links in the section down the bottom with the others. I also may have to move or make smaller the initial image of the olfactory system as I think it is stopping a table from formatting properly. If you are unhappy with any of those small changes I make please feel free to put them back or let me know and I will. Cheers.

Talk:2012 Group Project 3

2012-09-25T23:19:51Z

Z3254758: /* Group evaluation */

{{2012GroupDiscussion}}

--[[User:Z8600021|Mark Hill]] 09:54, 18 September 2012 (EST) This is a recent review on taste. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2922655 http://jcb.rupress.org/content/190/3/285 JCB content allows reuse.

==Group evaluation==
The overall set up of the page I think is very good. In the introduction there is a balance between pictures and text which makes it a bit easier to read. Also its easy to follow, the text itself isn’t confusing and is understandable.

There is a good overview of the different types of receptors and their function, also there is a brief section on the adult tongue which is good, however there needs to be more focus on the embryological development rather than just a simple table on that. There also needs to be some images added to that component as well to make it more understandable.

The sections on abnormalities and current research need to be organised a bit better because they are a little hard to follow, especially with the placing of the images. The glossary is simple and understandable, however there needs to be more work done on the reference list.

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The layout and balance between text and figures, tables, and diagrams is extremely well accomplished. All the information of the page is really intriguing and easy to follow on the majority.
I would suggest placing the history of discoveries immediately after the introduction so that readers may appreciate all the research that would have had to take place in order to put all the information on this page. As well, this would help in having a separation between the two tables used.

When it comes to images, make sure that everything in the image is relevant to the accompanying text and important to the reader. One image where you might fall short of this criteria, is the very first image on the page about the five basic tastes, the names of the protein structures is more distracting and confusing than enlightening and overall would not aid in informing the reader.

I believe the introduction is very important in assisting the reader in gaining an overall understanding of the page and it’s aims. Hence I believe it is important to include a more succinct introduction with such aims. In this case, the introduction to the gustatory system begins defining structures and functions which are better off used elsewhere. Instead try giving an overview of the system and maybe give the reader a reason to read on.

The images used in the abnormality section are scattered and make it hard for the reader to determine which image corresponds to which idea, I would suggest ensuring that each image is detrimental to aiding the reader’s thoughts. This was an extremely interesting section.

Current research is clear, concise and easy to follow with a pleasant arrangement of ideas, text, and images. It was interesting to read. Additionally, the references and glossary are extensive and well done. I would suggest having a link to the glossary from within the text.

Well done on your project so far, and good luck with the rest.

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The introduction seemed to go into a lot of detail. for example, the information on Type II receptors should be placed in the same section as neural pathways, not the introduction. Can you also include in your introduction, an overview of what you are going to talk about in your project? That would give your project more structure.

With the neural pathway section, can you draw or find a diagram for that section? I find it hard to understand without one. The taste map section goes into a lot of detail which I think is unnecessary because this is a development project.

Current research section is very interesting. I don't think you need to add any more content on that section - that section to me looks complete, besides a few formatting and referencing issues with the images.

Overall, I felt there wasn't enough written on the development of taste, either the receptors (taste buds) or the neural pathways. Your project seem to focus on the anatomy and physiology or function of the taste system. This is alright to keep but the focus should be on development. You do have a Time-line of taste development that summarizes the development of the Gustatory system which is great to see. I think use that as a starting point and expand on each stage in text form, below the table. In week 12 development in this time-line, you mention 'epithelial types I and II', what are they? Are they similar to skin cells?

Overall, the balance between images and text is great. The colourful images work wonders in breaking up the text. Having said that, Many of your images did not have the correct PMID referencing. These images include:
* images of taste being revoked by visualizing ATP release
* CVP of WT and DKO mouse with H & E and SEM
* histology - can you give a more relevant title for this image? We know it's histology; we can see that. What is this image about?
* Abnormal of Tongue - it should say abnormality of tongue

The history section is excellent because it spans over such a long time - 350BC to 2010. The layout of a coloured table for history is beautiful, clear and concise.

--[[User:Z3332863|Z3332863]] 16:35, 23 September 2012 (EST)

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- The introduction of taste is very descriptive and encapsulates the anatomy, physiology and cell biology. Although it is very detailed it doesn’t indicate that the project is about development.

- There is a lot of detail about the taste neural pathway and cortical areas which I’m not sure is relevant to olfactory development unless you mention how they develop as well.

- Figure 2 and 3 do not have any copyright information associated so remember to add those.

- The development section is very nicely put together and hopefully you will add images further down the line. I’ve noticed that in week 8 of development you have the same ref after each line…I’m sure you can just put it at the end of the paragraph as it is same for each line. Same goes for week 14 and 15. Also since you have 2 references for the entire section --- you might want to look at other articles as well.

- Some things that I missed in the section were patterning molecules and genes. Also any signalling mechanisms that control differentiation.

- The history section is exceptionally done with the use of tables, description and references.

- I thoroughly enjoyed your abnormality section. The images are nicely done as well. Although you have described many genes and molecules which are not specified in the normal development portion so the reader don’t understand their roles. Maybe address this in your normal development section.

- The current development section is also very nicely put together but again things like Shh and WNT should be in development section.

Overall very nicely put together and great balance of pictures and text. Although this is a development topic so the major emphasis should be on development of the organ --- Normal development is good but there is too much content in that section that can be left out.

--[[User:Z3333794|Z3333794]] 10:52, 23 September 2012 (EST)

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Abundant information, including a nice coloured in table, which is a cool idea. Unfinished though, the images to go with it would make it great. The page seems to be segmented into sections with a large amount of text, and sections with many pictures. Try for a more even distribution, if possible. Pictures seem to be relevant, with good explanations, referencing and certificates. Helpful and interesting abnormalities and current research sections

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Your introduction is quite good and gives us a brief overview of the different tastes. I also like it that you touch on the fact that it is important we recognise (via taste) food which would be dangerous to our health. In my opinion, after you mention the research (ending the sentence with …’may exist.’) you should tell the reader what you will be discussing on your page. The few lines on fatty acids does not seem to fit in, and should be part of your history section and possibly current/future research. Some specific information seems to have been researched, such as what umami codes for; however, references have not been provided. Also make sure that the image has the correct information – title, description, references, copyright, student template.

It would be more logical to put the history section next. Following this by the timeline and then go back to the cell biology, receptors and taste map etc.

The history section is good with many significant dates and clear descriptions incorporated in a table. I do see lots of numbers, which I think relate to references. I cannot find these references anywhere, so please edit this and make sure it is included in your list of references. There are also a few references listed in full in the table, so please put these down as proper references. Also, there is no good description for the year 2007 (it is mainly a reference).

The developmental timeline is expansive and very interesting! It really relates to the different developmental stages and tells us what happens over time. I hope you can include images with appropriate labels and information to this table, as it will greatly complement your text. Please do check your spelling, eg. ‘epithelium’ in week 6. Also references in this section are appropriate and are not doubled-up in the reference list. Do check reference 5 as it comes up with a cite error.

The section on cell biology and type 2 receptors is clear and easy to read. I cannot see any references though! Please be careful cause this might indicate plagiarism. The taste map is interesting and I am glad you mentioned research has indicated that the different receptors are in fact located all over the tongue – not just in particular sections. If possible, look for the original paper(s) that made this discovery.

The section on neural pathways is a little more difficult to read and I did not understand some of it. Particular terms are used in sentences which suggest little effort has been put in to explain everything in your own words. This is further indicated by the lack of references in the ‘first order neuron’ section and the majority of the ‘second order neuron’ section. I might be wrong, but then do add all your jargon to the glossary. If possible, also try to find other papers which present the same information to strengthen your points mentioned. Images for both the taste map and the cortex need referencing, copyright info, etc.

Adult tongue and taste buds. It is good you include some anatomy and physiology into your section. Do keep in mind the majority of your project should focus on embryonic development. You included the appropriate names, eg. sulcus terminalis, and I am glad to see that has also been put in the glossary. Some more terms do need to be added, eg. circumvallate. The text is good, clear and easy to read. Images are appropriate and relate to the text but need proper descriptions, citations, etc. A major let down of this section is the lack of references – please include this.

Personally, I found the abnormalities section very interesting! However, you are suddenly talking about all these genes and factors which you have not mentioned anywhere else. It might be good to provide a brief description of these in the development section or incorporate them into your developmental timeline. Images all have copyright information, but other information is missing, such as the student template and/or reference. Please check and add this.

Current research includes a lot of information. All different sections have their references which are displayed in the reference list. If you can, provide links to the website of the research groups working on current projects. Be careful not to just put your reference at the end, as you may also have to reference within the paragraph. Both pictures used will need the student template. The double tongue image will need a reference in its description too.

As mentioned before, add and edit the glossary and reference list. You should also add to the useful links (make this external links) and the image gallery, or delete these subheadings, as there is nothing there now.

Hope this helps!
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"In regards to the information presented (outcomes 1 and 9), the timeline for the development is good and written with clarity. However, I noticed the section on structure only referred to the adult state rather than focusing on the embryonic origin of each structure (ectoderm, endoderm and mesoderm). I would suggest that you elaborate on the developmental stages introduced in the timeline in order to build on the information you have already provided. This is important in regards to outcome 6 so that you can relate your research to embryology – the development of taste should be your focus. The history timeline was great to read as it was very concise and clear.

The page shows a good level of peer teaching with clear language and a good balance between images and text (outcome 4) with technical terms explained in the glossary. An improvement could be to make a link between any technical language and the glossary to avoid scrolling up and down to the page. Your Current Research section (outcome 5) was very interesting to read and showed you went beyond the scope of basic research on taste – good work!

In terms of layout (outcome 2), whilst the images are interesting and relevant to the text, some are not appropriately referenced nor described; make sure to reference appropriately and at least write one or two sentences to make the images relevant to the reader. Additionally, the introduction should not be under another subheading (Gustatory system) as it creates some confusion; I would suggest making the introduction its own heading in order to make the page flow. Similarly, the history timeline would best be placed towards the beginning of the page, under the introduction.

I noticed some areas (such as the section on Structure) were not appropriately or consistently referenced. Make sure to include a citation anytime you introduce a researched idea or information to avoid being accused of plagiarism. I noticed the history timeline had good consistent referencing; however the numbers just need to be formatted so they come under the reference list. If you click on the Tutorial: References page linked from the student page, it tells you how to do this. Hope the feedback helps and all the best for your project!"

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The introduction is very detailed but did not mention anything about the development of the taste. But I thought the mechanisms behind sweet and salty tastes are very interesting. Maybe do the same for the other 3 tastes? The image of the basic 5 tastes is a bit small, maybe upload a bigger version of the image. Also, the image is lacking some reference, copyright information and a student image template.

The type II receptor section is pretty good and descriptive but it does not really relate to the development of the taste. The taste map is a very eye-catchy image and it would be really useful if it had all the needed information such as the copyright notice. The timeline of the gustatory system is very well-presented and easy to read. I understand the project is not completed yet, therefore more images are still to be put in. Only 2 references have been used in the timeline section, maybe try to research more and use different resources. There are some citing error but it should be quite easy to fix.

Histories of discoveries section is very detailed and easy to read but the referencing needs to be fixed. The adult tongue and taste bud section is very clear and precise and contain a lot of useful information but it does not really relate to the research topic, should beware of going off-track. The hand-drawn diagram of the taste bud is impressive and easy to understand but again lacking in some referencing information such as who drew it. The abnormalities section is good and well-researched and it is interesting to know about which gene or receptors will effect the development of taste and sensation. Maybe the abnormalities section can be included into the current research section because abnormalities are repeated in the current research section below. There are detailed definitions of terms in the glossary which is good because it really helps the reader to understand more about the research topic.

Overall, the page is looking good. The main thing that needs to be fixed will be the images that are already on the page, they need the correct and essential information with them when uploaded on the page or else, they will get deleted and there will be no images on the page and the nice balance of images and text now will be gone. There seem to be a lot of anatomy and biology of the taste system but not a lot of information about their development. Although there is a timeline of development but i think more information is needed. Referencing is pretty good with only one or two minor citing error but it should be easy to fix. Structure of the page is clear and simple with headings and sub-headings being consistent, making the page easy to read and follow. Hope this helps :)

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The introduction is good, explaining the function and mechanisms behind.

The taste map text and picture are useful however lack referencing information.

The cortical areas section is very interesting and well referenced.

The table timeline is a very good way to summarise the development of taste. It is succinct and well referenced, even though one paper was referred to for most of the information.

The history table is similarly good, very succinct and straightforward, however lacks some references, and the references that were included could be improved by using the wiki referencing system.

The structure and function section is useful but doesn't add much to the text in terms of embryological development. Also make sure the images are properly referenced with the "student template" included.

The abnormalities section is very good and well researched, although maybe try and avoid referring to the articles that have been researched in the text and rather just refer to them using the wiki referencing system. The images are good as well but don't forget the "student template" here also.

The current research section is interesting and well researched, the use of succinct subheadings to summarise the paper's findings was good.

The useful links and image sections need to be added to, and the glossary section can be improved by putting the key terms in bold, but that is otherwise good.

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Initially the page seems to have a good balance between text and diagrams/photographs. However the figures included are not properly labelled once you click on the file and some of them don't appear to have any copyright information included. Some of the pictures could do with being a bit smaller as they take up a large proportion of the page. The student drawn image of the tongue is particularly impressive but does still need to have the student template included. The references seem limited in comparison to other groups perhaps suggesting a lack of depth or variety of research. There also appears to be a coding problem relating to reference number 5. The general layout and use of subheadings is great. It may be useful to link the words in the glossary to their occurrence in the text.

The introductory paragraphs are very well written. They are easy to understand and interesting and give a good overview of how taste functions. Similarly the section on taste map is well written clearly explaining the neurological factors associated with taste. However the presence of the picture in isolation is confusing as it is representing an the old method of taste association. Perhaps this would be resolved if a diagram of the newer taste map was also included. Also you say that the old taste map has been disproved by recent research but that research is not referenced. In fact it appears that very little of that section is referenced. The section on cortical areas is well done.

The timeline of developmental processes is good, the table an easy visual format and the information concise and effective. The only point of contention would be the direct quote in Wk8-9 which seems out of place in comparison to the remainder of the entries which are nicely paraphrased. The history section is similarly well done being extensive and comprehensive. That is excepting some Pub Med references which are just placed in the text rather than in the reference list at the bottom. While interesting and well written the part detailing the Adult Tongue and Taste Buds seems out of place in a embryology course.

The sections on the effect of gene expression on the formation of taste abnormalities and current research are good. However it may be useful to put the information regarding each picture as a caption rather than plain text.

It will be interesting to see what is put in the section "Image Gallery"

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The information provided is both informative and well organised. The use of tables and figures make the text easy to follow and the diagrams make the information easier to understand. When it comes to images however, they seem to be somewhat irrelevant next to some of the information in some cases. Try to move them around and make sure they accompany relevant text.

The introduction does not give the reader the overview of the topic, but rather explores structures and function which makes it difficult to order. Simplifying the introduction, and moving some of the more detailed information such as the information about the type 2 receptors to the relevant section would improve the page.

Other information that is difficult to understand is the text which involves certain genes and molecules without explaining their function or role. Explaining these aspects of the genes and molecules would make the information flow better.
The section on current research is very informative and seems to be complete. However, I did note some errors with the citation of the image used, working on the references is very important for the other images as well as not all have the copyright information.

I also noticed that many of the references are repeated numerous times. Week 8 of development for example have the same reference after a number of sentences. A variety of sources will improve the accuracy of the information rather than derive all the information from a single source.

There is a great focus on the anatomy and physiology of taste, however, it is important to remember that the focus of this project is about development, and therefore including a timeline or a table which covers this information is very important. The page seems to be very organised and the inclusion of tables and diagrams along with the extensive glossary make this page stand out. Well done.

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The page that you have created is very extensive and was well formatted in relation to the ratio of images to text on the page.
Found that the colours and use of table for the breakdown of information in relation to ‘Timeline of developmental process’ and ‘history of discoveries’ condensed the material and made it easily understandable. This made me want to keep reading.

With majority of the images that are uploaded onto the page there needs to be the correct information and referencing provided for the summary box. From where the image was sourced (ideally of reliable and scientific literature in origin), identifying that it has been uploaded for a student assignment and copyright information-permission to use uploaded image and any other information that is pertaining to the topic and why the image was used/relevant.
Further, those of you within your group that have drawn an uploaded image, have to ensure that you have stated in the summary box that it was student drawn prior to final assessment/evaluation.

The glossary is able to be expanded upon and potentially ensuring that the words that are being explained/elaborated are bolded. As a reader, I would find it easier to read and distinguish if they were bolded.
The reference list that has been developed appears to demonstrate that as a group you have are well read and researched, however, the citation errors will have to be addressed and resolved prior to final marking of the project. I really appreciated the layout (headings, summary and images) of the page.

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The introduction is well written and very informative. You should add the history timeline directly below the introduction, because where it currently is feels like it is floating. With it after the introduction it will create a flow to your page and separate the two tables.
In your development table I noted a column called images, the adding of images to show the development stage you are describing will give this section some more flair. If you are not adding images don’t forget to delete the column.

Your section on adult taste and tongue is very interesting but maybe if there is a difference, i.e. newborns tongues are more sensitive to a taste than adults, a comparison would be interesting here.

In abnormalities you mention p2x receptors, maybe you could add this to the glossary and give a brief explanation about what they are and do. This would be a good idea for any other receptor or genes/proteins mention above that you don’t want to explain in detail in the main section.
--[[User:Z3220343|Z3220343]] 21:31, 25 September 2012 (EST)

---

Your introductory paragraph is sufficiently detailed. However, there is only one reference. You need to show more research by adding more references to support your text. It is good that you have added an image to support the text, but you need to write that it is a student uploaded image.
Cell biology and type 2 receptors sections don’t have any references cited at all. You need to add appropriate references.

There was an image of the tongue showing the tastes in different sections of the tongue. The image didn’t have the source referenced.

The taste map section needs more referencing and citations.

Cortical area is sufficiently detailed and has appropriate numbers of references, along with a supportive image. However, you should add more description of what the image is about.
“Timeline of Developmental Processes of the Gustatory System” looks nice so far, with appropriate citations. But you may need to add some more information, and it needs to add images to support the text.

History of discoveries section looks nice, but needs a bit more texts explaining each of the discoveries. It also needs some more references, and perhaps adding some images to support the text would make it easier to visualise the discoveries.

“Adult Tongue and Taste Buds – Structure and Function” is overall lacking in text and needs more research and references. You need to explain more of the structures and functions of the tongue. The image of the ‘drawing of the tongue’ needs a bit more description in the caption. Perhaps explain what each of the labels mean. The papillae image should say that it is a student uploaded image.

Current research section is done reasonably well so far. The reference needs appropriate formatting. Perhaps reduce the size of the image showing the double tongue; it is rather graphic and somewhat disturbing.

You do not have any useful links listed. You need to add links.

Glossary section is good so far. Perhaps add some more words, and make the text bold to make it easier to spot the different words.

Image gallery does not have images under the heading.

References section: number 5 needs to be fixed.

There are not external links listed under the heading, you need to add external links with appropriate formatting.

----

Group 3- Taste

Overall this is an excellent project. Well written, great informative photos, good use of tables, and comprehensive information that's well explained.

A few of the photos don't have the appropriate copyright information and some sections of text haven't been referenced, but in general this ticks all of the boxes

----

==Questions for group==
--[[User:Z3330986|Z3330986]] 14:29, 18 September 2012 (EST)--[[User:Z3330986|Z3330986]] 14:29, 18 September 2012 (EST)
Hey guys,

Did I see someone write about or have articles about Sprouty (''spry'') genes?

I can't find it, but I'm sure I saw it. Let me know :)

--[[User:Z3332337|Z3332337]] 11:10, 18 September 2012 (EST)

--

Also, I've just been going over the main page and I wonder if a picture of the overall tongue, not only sections or histological drawings (which were really good btw) would be good to point out the anatomical features?? Like the sulcus terminalis which was pointed out.
I'd be happy to draw it. This would be for the Basic structure section.

Let me know ASAP so I can do it tonight :)

--[[User:Z3332337|Z3332337]] 11:30, 18 September 2012 (EST)

--

Yep, i think that would be a good idea. Go for it :)

--[[User:Z3330986|Z3330986]] 14:29, 18 September 2012 (EST)

Roger that (y). I'll have it done by around 10'ish tonight to be realistic.

--[[User:Z3332337|Z3332337]] 17:10, 18 September 2012 (EST)

--

Guys!!! I'm following image upload instructions to the letter and it keeps giving me database error. :( I need to upload figures 1 and 6 from this article. Let me know, k?

--[[User:Z3332337|Z3332337]] 17:58, 18 September 2012 (EST)

--
I had the same problem during the Lab assignments so i used a different image instead. I'm not sure if its related to the image itself? Maybe just email mark?

Maybe everyone could add some words from their relevant sections and hopefully we can come up with a pretty comprehensive glossary
--[[User:Z3330986|Z3330986]] 20:40, 18 September 2012 (EST)

== Discussion of Contributions via Email ==

Jared: hi guys,

just confirming our meeting tome tomorrow after the first lecture [after mid sem break]

Thanks :-0.

Nat:
Yup, meet outside the lecture room?

--[[User:Z3332337|Z3332337]] 11:07, 11 September 2012 (EST)

--

Hey Guys,

Jared :
becuase we are on holidays as of now, make sure we are communicating about any contributions and copy and past any email discusions onto this page.

--

Hey guys,
So here's our plan for the next few weeks. If you want you can start writing up a particular section before next week!

* Wed 5/09: Have heading finalized; divide work.
* Wed 12/09: Sections finished. Discuss in class of any areas of improvement.
* Wed 19/09: Peer Assessment!

Have a good break :)

--[[User:Z3289738|Z3289738]] 11:58, 29 August 2012 (EST)

--

Hey guys,
I thought of a few headings, please let me know if you have anything to add or change!

* Intro
* History of discoveries
* Gustatory system - this is really important!!
* Tongue and taste buds - structure and function
* Taste map
* Weekly development
* Abnormalities
* Current Research
* Future research

Not including the intro we can each choose 2 areas. I'll get started on History of discoveries and Weekly development.

If you're having problems with your section, or feel that it is irrelevant, or find something else along the way just email the group and we can make changes!

Have a great week :)

Nat

--[[User:Z3289738|Z3289738]] 10:58, 5 September 2012 (EST)

--

That sounds good, maybe we should try and meet before next wednesday to make final changes?

--

Sure, how about somewhere between the two Embryology lectures (12-3pm) on Tuesday?

Which sections do you want to do? I just put them up on our wiki page.

Nat --[[User:Z3289738|Z3289738]] 11:35, 5 September 2012 (EST)

--

well i have been already doing current research and structure + development, but im happy to do more work :) and yes perhaps straight after our fist lecture 11-12pm?

--

Jordan --[[User:Z3330986|Z3330986]] 11:50, 5 September 2012 (EST)

Hi everyone i'll be happy to "Gustatory system" and "taste map." I think it would make it a bit easier as i have covered the neural pathways of taste in some detail in Neuroanatomy.

--

Okay awesome guys

So the division of work so far is:
* Introduction to the Gustatory System - '''Jordan'''
* Timeline of Developmental Processes of the Gustatory System - '''Nat'''
* History of Discoveries - '''Nat'''
* Adult Tongue and Taste Buds – Structure and Function - '''Jared'''
* Taste Map - '''Jordan'''
* Abnormalities - '''Liz?'''
* Current Research - '''Jared'''
* Future Research - '''Liz?'''

Liz are you happy with those sections?

And Jared be careful with the 'Taste Maps' section, I just read that it may be a misconception! If thats the case then maybe just how the brain interprets the 5 different types of taste.

Nat
--[[User:Z3289738|Z3289738]] 11:56, 5 September 2012 (EST)

Hi guys,
Yes I'm happy with these sections and am on it.

Liz
--[[User:Z3332337|Z3332337]] 13:46, 6 September 2012 (EST)

--
Hi,

Can someone help me with image uploading?

The website say okay to use for commercial etc...

this is the link, is that enough information to get around copyright ????
http://embryology.med.unsw.edu.au/embryology/index.php?title=File:Structure_of_Tongue.gif

Thank you, Jared

hi guys,

just confirming our meeting tome tomorrow after the first lecture.

Thanks :-0.

== Useful articles ==

Hi there,

I'm going to links to the articles I find here so you guys can see them and I don't lose them.

===Future Research===

1) A Test for Measuring Gustatory Function
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2823587/?tool=pmcentrez]

This is pretty good for future methods of detecting defects in taste, but requires communication about reception of the tastant. Could be used when the children grow up. Great for adults.

2) The gustatory cortex and multisensory integration
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2726647/?tool=pmcentrez]

3) REWIRING THE GUSTATORY SYSTEM: SPECIFICITY BETWEEN NERVE AND TASTE BUD FIELD IS CRITICAL FOR NORMAL SALT DISCRIMINATION
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2812680/?tool=pmcentrez]
(Not sure where I would put this, I'm going to put it in future research]

===Abnormalities===

1) Gustatory Imagery Reveals Functional Connectivity from the Prefrontal to Insular Cortices Traced with Magnetoencephalography
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3132751/?tool=pmcentrez]

This article essentially highlights that taste imagery is a learned response in the Insular Cortices (IC), imaged by fMRI and PET scans, and that disruption in this learning process changes the way we perceive taste. Again, I don't know how relevant this would be in the developing embryo unless there would be damage in the pre-frontal IC.

Any ideas guys??

2) Defects in the Peripheral Taste Structure and Function in the MRL/lpr Mouse Model of Autoimmune Disease
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3334929/?tool=pmcentrez]

3) Knocking out P2X receptors reduces transmitter secretion in taste buds
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3188419/?tool=pmcentrez]
<pubmed>21940456</pubmed>

This was a GREAT article. Basically spoke about how using double knockout (DKO) mice for taste receptors P2X2 and P2X3 were knocked out and how it didn't release the neurotransmitter ATP when a tastant was administered, whereas the WT (wild type) mice did release ATP.

--

4) Taste Function in Mice with a Targeted Mutation of the Pkd1l3 Gene
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2924428/?tool=pmcentrez]

<pubmed>20605874</pubmed>

5) FGF Signaling Regulates the Number of Posterior Taste Papillae by Controlling Progenitor Field Size
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3107195/?tool=pmcentrez]

<pubmed>21655085</pubmed>

6) Taste receptor cells arise from local epithelium, not neurogenic ectoderm.
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2924428/?tool=pmcentrez]

<pubmed>7892199</pubmed>

7) Downregulation of Dlx5 and Dlx6 expression by Hand2 is essential for initiation of tongue morphogenesis
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3091495/?tool=pmcentrez]

--[[User:Z3332337|Z3332337]] 15:30, 16 September 2012 (EST)

===Other??===

1) Olfactory and Gustatory Sensory Changes to Tobacco Smoke in Pregnant Smokers
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3375030/?tool=pmcentrez]

This article is unrequired for this specific project (I realised this AFTER i read most of it) because it talks about how pregnancy affects the 'want' to smoke. So it's more behavioral rather than research into developmental problems that smoking may cause.

2) CODING IN THE MAMMALIAN GUSTATORY SYSTEM
[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2902637/?tool=pmcentrez]

Liz
--[[User:Z3332337|Z3332337]] 14:09, 6 September 2012 (EST)

----

Hi guys, just putting a subheading of interesting articles found:

'''1.''' <pubmed>21978088</pubmed>

'''2.''' [http://embryology.med.unsw.edu.au/notes/tongue.htm#17108952 UNSW Embryology Development of Taste]

This website provides a really great overview of taste developmental timing & overview, tastebuds, receptors, pathways, genes and provides great references for further research - and its a UNSW site!

'''3.''' [http://www.sciencedaily.com/releases/2006/12/061205214617.htm Researchers Discover Initial Steps In Development Of Taste]

A Science News story that looks at the role of Wnt pathway in the development of taste. "In the present study, the researchers found that in mice in which the actions of Wnt proteins were blocked, taste papilla buds completely failed to develop. Conversely, in mice in which Wnt signaling was over activated, their tongues were covered with many and large papillae and taste buds." It also briefly discusses neural pathways of taste and abnormalities.

'''4.''' Purves D, Augustine GJ, Fitzpatrick D, et al., editors. Neuroscience. 2nd edition. Sunderland (MA): Sinauer Associates; 2001. '''Taste Receptors and the Transduction of Taste Signals'''. Available from: http://www.ncbi.nlm.nih.gov/books/NBK11148/

This book chapter covers a variety of transduction mechanisms for taste cells. It is quite detailed, however has some great diagrams to explain the content. The concluding paragraph provides a good summary: "The overall picture that emerges from these admittedly complicated details is that taste cells have a variety of transduction mechanisms. In general, individual taste cells respond to several types of chemical stimuli. Nevertheless, taste cells also exhibit gustatory selectivity. Like olfactory cells, the lower the threshold concentration for detecting a single tastant, the greater the selectivity of the relevant taste cell. Finally, taste receptor mechanisms also adapt to the ongoing presence of a stimulus, although the mechanisms are not understood. If a chemical is left on the tongue for a sufficient time, it ceases to be perceived (consider saliva, for example). Thus, to obtain the full taste of foods, one must either frequently change the types of foods placed in the mouth or wait a sufficient time between helpings, facts that have long been appreciated by restauranteurs and gourmets."

'''5.''' <pubmed>17108952</pubmed>
This article describes the receptors and cells involved in the different types of taste (sweet, sour, bitter, salty and umami).

'''6.''' <pubmed>17287575</pubmed>
This review focuses on the development of fungiform papillae in rodents.

'''7.''' <pubmed>15581865</pubmed>
This article focuses on the role of Sonic hedgehog on tongue and taste papilla development.

'''8'''
Liu HX, Komatsu Y, Mishina Y, Mistretta CM.
http://www.ncbi.nlm.nih.gov/pubmed/22659543
This is an article about neural crest contributions to taste development

--[[User:Z3289738|Z3289738]] 10:44, 22 August 2012 (EST)

----
Remember: textbooks are a good foundation, but articles are best to gain info from.

--[[User:Z3332337|Z3332337]] 11:32, 29 August 2012 (EST)

Hey, Just need somewhere to put this:
*[http://embryology.med.unsw.edu.au/embryology/index.php?title=Sensory_-_Taste_Development Sensory Taste Development; UNSW Embryology]
*[http://www.ncbi.nlm.nih.gov/pubmed/8955790 Embryonic and early fetal development of human taste buds: a transmission electron microscopical study] <ref name=PMID8955790><pubmed>8955790</pubmed></ref> - Can't access full article!
*[http://www.ncbi.nlm.nih.gov/pubmed/9455607 Scanning electron microscopical studies of developing gustatory papillae in humans.] <ref><pubmed>9455607</pubmed></ref>
*[http://www.ncbi.nlm.nih.gov/pubmed/9541477 Innervation of developing human taste buds. An immunohistochemical study] <ref><pubmed>9541477</pubmed></ref>
*[http://www.ncbi.nlm.nih.gov/pubmed/8241557 Evidence for stimulus access to taste cells and nerves during development: an electron microscopic study.] <ref><pubmed>8241557</pubmed></ref>

--[[User:Z3289738|Z3289738]] 11:24, 19 September 2012 (EST)

== Headings==
* Introduction
* History of Major Discoveries (early researchers)
* Time line of Developmental processes
- this is the major focus of the project (ie: developmental processes)

- week by week
** Tongue
** Taste
* Final Structure and Function of the Tongue
* Abnormal structure and function
^ these 2 can be minor sections.
* Technologies to detect abnormalities during pregnancy?
* Current research (recent findings)
* Glossary and Abbreviations
* References

--[[User:Z3332337|Z3332337]] 11:30, 29 August 2012 (EST)

Notes from Mark Hill:
* Origins of sensory
* Central pathway for taste
* Neural crest contributions
* Overview diagram of sensory diagram (can be hand drawn)
* Journal of Cell biology - Taste [http://jcb.rupress.org/content/190/3/285.full JCB]
* Links between taste and smell
* Tongue has muscular and sensory functions - segregate the two

==Division of Work==

Natalie - Normal function & abnormal function

Liz - tongue & taste development

Jordan - time line of discoveries

Jared - structure & function; recent findings

==Topic Choice==

Hey guys,
Unfortunately a lot of other groups seem to want to do hearing & vision as well, so I thought maybe we should choose to do '''taste'''. Let me know what you think!

I also brainstormed a few topic headings... feel free to add to it or change the order around

Headings:
* Introduction (what is the project about?)
* Time line of major discoveries / History (early researchers)
* Structure & Function
* Tongue development (brief)
* Taste development - time line and detailed
* Normal function
* Abnormal function
* Current research (recent findings)
* Glossary and Abbreviations
* References

--[[User:Z3289738|Z3289738]] 11:42, 15 August 2012 (EST)

----

==Lets do: Sensory - Hearing==

From a bit of research this afternoon, I couldn't find much on skin development in terms of "sense organ"/"sense development". I suggest if we do Sensory we do hearing as there was alot of information (inner, middle, outer). And also there are specific screening procedures involved during pregancy.

Couple of link below with basic surface information that we could use as a starting point.

[http://cwx.prenhall.com/bookbind/pubbooks/martini10/chapter18/custom3/deluxe-content.html]

[http://www.spuc.org.uk/education/abortion/human-development]

----

Hi guys

Organ = liver

Sensory = vision / skin / hearing

--[[User:Z3289738|Z3289738]] 12:02, 8 August 2012 (EST)

really usefull website including information on phisiology etc
[http://www.cf.ac.uk/biosi/staffinfo/jacob/teaching/sensory/taste.html]

== Stucture & Function ==

'''Structure/ Parts'''
general including tissue type muslces + mucosa etc

- anterior 2/3 and posterior 1/3 (sculus terminulis)- we are manily concerned with 2/3 of tounge as it responsible for papillae + soft palate and epiglottis containing
- papillae, contain chemo-recpetors

'''Function'''
- direct vs indriect
- parts of tounge detecting differnt tastes/ flavours

'''Pathway'''
chmeorecpetors (translation/ transduction)
process of chemical to elecectrical

Talk:2012 Group Project 2

2012-09-25T23:17:55Z

Z3254758: /* Group evaluation */

{{2012GroupDiscussion}}

--[[User:Z8600021|Mark Hill]] 09:57, 18 September 2012 (EST) This is a recent review on touch. http://jcb.rupress.org/content/191/2/237.full JCB content allows reuse.

==Group evaluation==

Initial impression is it’s too textual for a wiki. The lack of consistent referencing styles is hard to follow.
Relates the developing somatosensation to the nervous system, which was good and very interesting.
Tables and mind maps/flow carts would be beneficial in sections 1.3.1-1.3.3.
And a section on abnormalities of touch would be nice and/or methods of detecting touch and pain etc (ie: clinical methods) and maybe sensitivity to touch.

However, the way this project was divided was logical and easy to follow. But more defined and succinct paragraphs need to be made as it tends to go on for a bit, but that is a sign of good research into the project.

In the section of thermoreceptors it would be better if there was an image from the article for graphical representation.

Summary: MORE IMAGES!!! Be more succinct.

Good luck with the rest ☺

----

"The introduction is good in that there is a description of the role of somatosensory functions as well as an overview of its development. To improve further, perhaps avoid trailing off in the final sentence and perhaps put something that concludes your introduction.

In regards to the information presented and layout (outcomes 1, 2, 4 and 9), the history of discoveries is very brief and requires more research. Additionally, it would be useful to set up a timeline to add interest. The section on the central somatosensory differentiation appeared very well researched with a very interesting picture to accompany the text – good work. The section on Touch would better be placed in a table and have accompanying images to avoid getting too ‘wordy’. Also, this section does not have any consistent referencing in the bulk of the content – please cite where you find your information. The section on pain is well researched and has a strong content, however, to enhance this section I would suggest using dot points to describe the different fibres and add a relevant image. Similarly, the hot/cold and pressure sections were great in terms of content but could use with some dot points and visual explanation to make the page more interesting. Just a note on pressure – avoid getting repetitive; the page had already defined the Ruffini’s endings/corpuscles etc in the section of Touch. Additionally, the 2 urls at the bottom of this section are distracting, make sure to incorporate these in your reference list of add them to an ‘External Links’ section. Your Current Research section requires some proof reading and additional articles to make it more comprehensive. However, you have referenced the image well and referred to it in the accompanying text.

In terms of referencing, I noticed some areas where the in-text references were not correctly formatted and were in the (Author, date) style. Perhaps have a look at the referencing tutorial on the Embryology ‘Students’ page to get an understanding of the codes required for citations. For peer teaching (outcome 4), make sure that you define all technical terms – your Glossary only has 2 definitions provided. Other than this, the content overall is interesting to read just make sure you are striking a balance between images and text. Hope it helps and all the best!"

------

- The introduction is small yet detailed --- I like how its an overview of the development. You do need to fix up the references though.

- You have in the intro section “the following picture….” But there is no picture there….if the picture is further ahead maybe write Fig 1 shows….and also label the picture.

- History section needs a bit work on – you should start with the earliest data and proceed in a chronological order so everyone can see the advancement in development of somatosensory organs.

- In the section of “Development of the primary somatosensory cortex” you have mentioned that there are intrinsic and extrinsic mechanisms --- you should mention what those signalling mechanisms are. Also if you are using the one ref for the whole paragraph do not put the ref after each line. Just put it in the end. Also it would be good to give the origin of the neurons like ecto, endo or meso.

- Its good how your description is divided into stages – it might help to give the weeks as well.

- For the touch section you have a lot of detail on what the receptors are which is fine but there is nothing about their development (which is what the project is about). The same thing is noted with “Pain” section – there is nothing on development. I’m sure you can put some genes or signalling molecules that are important for differentiation of cells into the different receptors.

At the moment your project is focused on what the different somatosensory receptors do but very little detail on how they develop, which is what you need to focus on.

More pictures are needed to break up the text.

Good luck!

--[[User:Z3333794|Z3333794]] 09:51, 23 September 2012 (EST)

--------

Overall, the key points relating to the topic area are being addressed. The use of current research to develop ideas and provide detail to the separate sub-headings is helpful. However, I would suggest better collaboration amongst team members about what is going to be addressed under each sub-heading because some repetition has taken place, particularly between touch and pressure where overlaps are expected occur.

Additionally, there is clear imbalance between text and images and there are some areas where dot points, tables, images or videos will be better received by the audience than paragraphs of information.

More specifically, the history of discoveries can be tabulated and should include more historic events that may have taken place before Weber and possibly led to his research.
In the section on pain, the bulk of the information can look more easy to read if the different fibres are bolded and put on separate lines with their accompanied descriptions or images or videos are used to replace the text.

A diagram or flow chart may be used in the hot/cold section accompanying or replacing the description on the sensation of temperature.

The section on pressure has all information cramped up in one paragraph which presents different ideas. I suggest each idea being put under a different heading or paragraph. For example, a paragraph on development, one on different structures and their functions (if needed since already addressed), one on research and applications. Images could be helpful!

So far current research looks promising and with the inclusions of more projects, would be interesting. I would suggest only including images in the research section when they can be simply understood and impact on the reader’s understanding or interpretation of the project.

The student diagram used in describing the somatosensory pathway is well done and makes a big difference to the page. The layout of this section is also organised and easy to follow and comprehend.

The references, although extremely extensive, is inconsistent between sections and a consensus should be met amongst team members, additionally, the glossary needs to be built upon. The inclusions of more definitions may help in limiting the text in each section.

Overall, there is no critique on the information presented on the page, it is all very interesting and current, however, a change in organisation of information will help bring this to the attention of the reader.
Good luck!

--------

Your introduction is quite expansive and the first paragraph gives an excellent overview of what the somatosensory system actually is. At the end of the first paragraph you do refer to a picture; however, there is no picture. Please add this to show the somatosensory organisation within the body. In the second paragraph you mention some key timepoints related to the somatosensory development, which is good. After this (“Development of the system entails…lemniscal system.”) the text is probably too specific for the introduction. This can be used as an introduction for your development subheading. Please make sure that you edit the in-text references to proper references which we can access via your reference list. Also make sure you start adding terms to the glossary, eg. dorsal column-medial lemniscal system (I do not know what this means!)

You have started on your history section, but it would be more interesting and easier to read if you put this in a table. For instance: date – description – significant person. Also try to add a few more important discoveries. Again, please provide proper references. See the ‘editing basics’ section on this embryology website.

The central somatosensory differentiation is good and I can see that a lot of effort has been put into this section. The picture is very helpful and complements the text. To some extend it does seem like the sensory neurons only come from the dorsal aspect (going into the dorsal root ganglion), so maybe put a note in there that the dorsal and ventral rami are mixed nerves and both of them will contain sensory neurons that go to the dorsal root ganglion. With this image, you also have to include the student template. Text and references are good in this section and I particularly found the ‘making connections’ section very clear, organised and enjoyable to read. Do make sure that you add to the glossary – in particular terms from the ‘development of the primary cortex section’, and if possible add more images.

The touch section has a fair amount of text, but no images to complement it. This made it a bit boring to read. Make sure the subheadings stand out by making them bold. Most of the text has not been references at all, which is concerning and could potentially indicate plagiarism. I also did not read anything about the development of the various receptors (or hypotheses it no distinct evidence has been provided yet). Keep in mind we are looking at the development of the system, not the physiology. You did put in some interesting facts, such as that cell abnormalities can lead to Merkel-cell carcinoma.

Pain and hot/cold are similar to touch: good description of the physiology, but no development included. References are only provided as in-text citations or listed below, which will need to be edited to include them into the reference list. Include images to complement your text and engage the reader – this also concerns the touch section.

The pressure section has limited information regarding the development. Please include how this develops – what factors are included etc. In my opinion there is too much focus on the adult physiology. We are studying embryology… As mentioned above, please edit references and include appropriate images.

Current research looks good with an interesting image and the appropriate references, copyright and student template. The description helps to understand the image. Maybe add another research project to this section.

Add to the glossary, references and actually name the external links listed as 1) 2) and 3).

Hope this helps!
------

The introduction is very detailed and precise, and it really prepares the readers for what is going to be covered within the project. I thought it was a good introduction but the referencing needs to be fixed up because it looks really different too all the other parts of the project. I do not think that style of in-text citation is needed for the purpose of this project. The histories of discoveries will look better if it is in dot-points, it would be so much easier to read.

In the central somatosensory differentiation section, you mentioned that there are three components, but to me, only the primary somatosensory cortex has been extensively researched, i think more research should be done on the other two components. There is an imbalance of information between the three components. Also, I can see that only 2 references have been used in this entire section, maybe this is why there is an imbalance of information. Using a large variety of resources will definitely expand your knowledge and enable you to put in more information in this section. I thought the hand-drawn image was impressive but the colour is a bit vague and hard to see. A larger version of the image should be uploaded so that it is easier to see.

The "making connection" section has very good description on the physiology and the signalling process of CNS but I do not really understand the stages? Are they the stage events that are involved in embryonic development? Some more detailed explanation is needed here, and maybe some images will help?

The touch section has some good information but again only 2 references have been used which shows the need for further research. Images should be put in here because right now it is very crowded with text. Also, the same problem keeps occurring throughout the project, I feel like there are lots of information about the function of different components of the somatosensory system but not how they are developed. Make sure you do not go off track. There are some weird referencing in the hot/cold section which needs fixing up. There are nothing in the glossary, scientific terms and definition should be put here because not everyone will understand the terms used within the project page. The structure of the project was good though, very clear and simple which makes the page very easy to follow.

Overall, the page is looking good but maybe more research should be done and more images should be put in to balance with the large amount of text. Also, keeping the information related to the research topic will be a huge aspect to focus on. Hope this helps :)

Group Assessment Criteria:
# ''The key points relating to the topic that your group was allocated are clearly described.'' The introduction outlines the importance of the somatosensory system and provides a good summary of the developmental stages. More emphasis could be made on the key points of the project page.
# ''The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area.'' The content shows an understanding of the topic area, however the layout makes the text difficult to follow. There is not a clear connection between the ‘Central Somatosensory Differentiation’ and the somatosensory system. There is a lack of diagrams, tables and graphs to explain the written content.
# ''Content is correctly cited and referenced.'' Some sections are correctly referenced whilst others are completely lacking. This area needs working on.
# ''The wiki has an element of teaching at a peer level using the student’s own innovative diagrams, tables or figures and/or using interesting examples or explanations.'' The information is broken down well by headings and subheadings, however there is a lack of relating images to compliment the information. The one student drawn image is very useful.
# ''Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities.'' The information provided is well researched and satisfies the aims of the project in terms of developmental stages, however in order to go ‘beyond the formal teaching activities’ it needs to include sections such as abnormal development and more on the history, current and future research.
# ''Relates the topics and content of the Wiki entry to learning aims of embryology.'' The topics and content relate to the learning aims of embryology by describing the developmental stages if the somatosensory cortex.
# ''The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic and covered the key areas necessary to inform your peers in their learning.'' There has been a fair amount of research into the topic, however a bulk of the information is focused on descriptions of each of the senses. More emphasis should be placed on the development of each of these sense as that is the key topic area.

Additional points:
* The Introduction and Central Somatosensory Differentiation sections were well written and the accompanying diagram was very useful.
* The layout of the page could be improved with the use of tables and diagrams to reduce/replace the amount of text
* The project seems largely incomplete; more research needs to go into the History and research sections and there is a lack of images

----

The key points are clearly presented at the top of the page efficiently formatted allowing viewer a perfect insight to the entire pages content.
There is a severe lack of visual stimuli; this makes the page present as boring and text heavy. Image citation is commendable although throughout the test there is unacceptable links to external sites that are not explained with a messy reference section. The information presented is quite detailed and promotes a significant amount of research and understanding, it is put forward in an excellent matter.
Attempt to relate to the learning aims of embryology are apparent.
There is a large amount of information presented in a fantastic way although the lack of visual stimuli takes away from the final product; this along with the tidy up of referencing needs to be addressed.

--[[User:Z3330795|Z3330795]] 10:36, 24 September 2012 (EST)

----

The introduction provides a good overview however using the wiki in-text citation system will make it neater.

The history section has made a good start but this can be elaborated on further. Once again, referencing can be improved here.

The central somatosensory section has been well researched and the referencing is good. It would be preferable to label figures as "figure 1" etc as this makes it easy to refer to. The drawing is good and has a good explanation however the "student template" should be added.

The touch/pain/hot and cold/pressure sections have a lot of information on their function but not so much information relating to embryological development. Some sections are well referenced, other bits are referenced without the wiki format, and other sections aren't really referenced at all. This can be improved. Adding pictures to these sections to illustrate points will also be helpful.

The current research section, although small, is very good, well referenced, good inclusion of the figure however this could be given a name such as "figure 2". Adding more current research with variation in the topics covered will make this section even more interesting.

The glossary and external links are good - keep adding to these throughout the project.

----
This page has made good use of subheadings ensuring that the main topics are easily accessible from the contents box. The project appears a little text heavy, it may help to include some other images. Also don't forget to add the student template note on the student drawn image. The reference list at the end is not particularly extensive. Perhaps this can be worked on by collecting the loose references in the text and adding them to the final reference section. Overall some sections of the page seem to have little to with embryology and more focused on adult function.

The introduction, while good, seems to lack any original voice, rather seeming to consist almost entirely of research done by others. The referencing in this section is also confusing with (Lagercrantz, Hanson, Evrard & Rodeck, 2001) being listed before any text. Referencing in this format also makes the page seem like a report or essay rather than a web page. There is also mention of a picture that does not exist. The historic section is brief and rather hard to digest as it is just a chunk of text. Perhaps putting this information into a table and developing it a little would help here.

The section on Central Somatosensory Differentiation was particularly well done. The inclusion of the student drawn image making all the difference. The general structure of this section is also commendable.

The subtitles "Touch", "Pain", "Heat/Cold" and "Pressure" are somewhat abrupt and don't particularly indicate what the section is discussing. This section in particular could do with the addition of some images. The information under Touch could perhaps be a little more heavily researched but is generally well written. Breaking the Pain section into some smaller paragraphs could be useful. The Hot/Cold and Pressure sections are well done excepting the random references to some articles.

Current research section could do with some more information. There are several words throughout the content that could do with being linked to an explanation in the glossary such as the "dorsal column-medial lemniscal system". The external links section is a good addition but it might be helpful to explain more clearly what each links to, especially the last three.

----------------------
The introduction for somatosensory is very informative and the overview of its development is great. The information is also great, however i do notice a bit of overlap throughout the page. It is important to go through the information and remove information that is repeated.

At times it feels like there is far too much information and not enough images, tables and diagrams. Dot points would be an alternative way to present your information as organisation is necessary. Including some tables and breaking up the texts into more subheadings would make the information easier to absorb.

The history section requires some attention, and it is important to put it in a chronological order.
A number of references were not cited correctly and this needs to be corrected. It is important that you refer back to the tutorial on referencing as the citations are very important. Your glossary needs to be worked on and extended, it simply does not cover enough words within your project.

Where is the development section? This is one of the most important topics in the project in addition to function which need to cover signalling molecules and genes. The section on pressure however, is great, but the information needs to be put into tables or under more subheadings to make the information easier to read. At the moment information seems to be all over the place.

The current research section is great and should be expanded upon. The self drawn diagram about the somatosensory pathway is very informative and easy to understand. The references are great but some are included more than once and these need to be organised at the end of the page.
Beside the limited diagrams, images, tables and organisation this page looks very promising. Good luck

----
'''Somatosensory'''

Sectioning off the touch, pain, hot/cold and pressure was a very well thought out idea, but wouldn't hot/cold come under a temperature? Just an idea to change the heading to something a bit more formal. Overall the content was very well written. And most sections were referenced properly. Other sections were not, such as the introduction and pressure. The content in these paragraphs is so well written, I fell it is left down by the referencing problem. I found that there were only a few references used in some sections, and sometimes being only one. That may be because there is not enough information out there, I'm just not entirely satisfied with the amount of references. I feel there's more out there.
The hand drawn picture was very well done and I like it.
The Touch section was well done but had no developmental development, current research is lacking and as is the glossary.
There needs to more pictures also.

----
The introduction is thorough and explains what your topic is about. The history of discoveries part if that is all the info you can find, why not put it in a table it would format the section so the reader can get an overview on how our understanding on somatosensory began.

Your page could do with adding some more pictures in relation to the different sections of somatosensory. for e.g. you mention Meissner's corpuscles in the touch section, you could add a picture with labels so that people could have a visual to understand, as you state where they are located but lay people would not understand what dermal papillae are.

I see you have an embryology and development part with no information, hopefully this will be added to in the near future otherwise don't forget to delete it.

You should also add more to the glossary and have a part called external links and place your links there.
--[[User:Z3220343|Z3220343]] 21:30, 25 September 2012 (EST)

----

Your introductory paragraph is very detailed and has appropriate references. It would be nice to add an image to complement it somehow. Because it’s not very easy to read a big block of text without any image supporting the text. It would look more balanced that way. Also, providing clickable links to the references would be better and make it easier for users to find the original references by clicking on the citation rather than scrolling down and manually looking for the citation in the references.

History of discoveries section is somewhat lacking in content, you need to add more information. It would be nice to do a timeline format to make it easier to see the transition of new discoveries over the past years. Again, adding some images to support this section would make it more interesting to read. Again, providing clickable links to the references would be better and make it easier for users to find the original references by clicking on the citation rather than scrolling down and manually looking for the citation in the references.
“Central Somatosensory Differentiation” is the best section so far. It is very well detailed with appropriate references and has an image to support the text. It even has clickable reference links which is good, as it makes it easier to find the references. It would be good to add a little bit more information to describe the image. And perhaps add a few more images to support this section.
Overall, you only have one image on your entire page. It would be good if you add some more images to support your text.

Current Research section needs more articles about current research. One article doesn’t seem sufficient. It is good that your image from the article has the appropriate reference.
Glossary section needs more words and definitions, there is not enough so far.
Some of the external links needs to be fixed. You need to change the format of the links and explain where the links would take you or what those web pages are about.

----

Group 2- Somatosensory

-Great introduction. Really puts the project in context and justifies the importance of your research. Citations need to be formatted like the rest of the page

-History of discoveries-very poor syntax, word repetition and no paragraphs. What is Weber's full name? This is entitled "history of discoveries" when it is actually just a very brief, nonspecific summary of "Weber". What about the other interesting discoveries from various scientists over decades?

-Adult Central Somatosensory systems- ascending in what? Position? Importance? Activity? Sensitivity? This needs a more informative opening sentence.

-Trigeminal system and Development of the Primary Somatosensory Cortex- are well explained and ideas are presented in a logical, flowing manner. Great picture with a good description and referencing (impressed you drew it).

-"making connections between...." what do the stages mean? Why does it start at stage 23 instead of stage 1?

-touch/touch receptors is good but where are the references?

-pain and pressure sections also good but needs paragraphs and the formatting of citations is incorrect

-bullet points in pressure section need a brief sentence introducing their purpose. Papers listed at bottom of section should be correctly cited instead of having hyperlinks

-interesting info in temperature

-current research- maybe you could put the name of the paper and authors and explain how they conducted their study? That would help with understanding the nice picture

-Glossary is incomplete

-Needs more pictures

-minor grammatical and spelling errors throughout but overall very good and well sequenced.

==Search==

Hi, whoever wrote the history section, can you include some dates as to when the discoveries were made. I was thinking of putting that info into a table but we need the dates to do that. Thank you. --[[User:Z3332863|Z3332863]] 14:50, 15 September 2012 (EST)

[http://www.ncbi.nlm.nih.gov/sites/gquery?term=golgi+tendon+organ+development search pubmed GTO development]

'''Development of Nociceptors, Thermoceptors,and Pruriceptors'''

Lopes C, Liu Z, Xu Y, Ma Q. '''Tlx3 and runx1 act in combination to coordinate the development of a cohort of nociceptors, thermoceptors, and pruriceptors.''' J Neurosci. 2012 Jul 11;32(28):9706-15. <pubmed>22787056</pubmed>

'''Review for general Somatosensory development''' - just for background knowledge:

<pubmed>7812142</pubmed>
--[[User:Z3332863|Z3332863]] 14:53, 23 August 2012 (EST)

'''Central sensory Neuron development:'''

<pubmed>2918087</pubmed>
--[[User:Z3332863|Z3332863]] 14:53, 23 August 2012 (EST)

'''Article on Pain Development:'''

<pubmed>16446141</pubmed>

--[[User:Z3332863|Z3332863]] 10:05, 22 August 2012 (EST)

I think it would be cool to do an organ, but i'll be just as happy to do one of the senses. Does anyone have a specific organ they were thinking of?

My preference was '''Sensory''', but if we get organ that's fine also. If we did do organ I still want to look into some of the topics before I give my opinion, depending on the research and information behind it. If we got sensory, sight could be cool? - ==[[User:Z3330539|Z3330539]] 08:26, 10 August 2012 (EST)==

I'd prefer '''Sensory'''.

I agree; if we got Sensory, I would be happy to do '''Sight'''. But if we got Organ, I want to do the Heart but I'd be just as as happy to do another organ if anyone's keen.
--[[User:Z3332863|Z3332863]] 09:14, 10 August 2012 (EST)

Hi all,

I started with; and have mainly been looking into development relating to "Touch" and the receptors involved and time at which this occurs. I am happy to keep going or do research on the other categories as well? I will share what I found when we meet next. --[[User:Z3330539|Z3330539]] 22:02, 20 August 2012 (EST)--

User:Z3254758

2012-09-25T22:59:03Z

Z3254758: /* Peer Review */

==Lab Attendance==

--[[User:Z3254758|Z3254758]] 10:04, 25 July 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:35, 1 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:09, 8 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:04, 15 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:15, 22 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:05, 29 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 11:08, 12 September 2012 (EST) arrived at 10:10am

--[[User:Z3254758|Z3254758]] 10:02, 19 September 2012 (EST)

Ciliary Body
Iris
Cornea
Aqueous Chambers
Lacrimal Glands
Extraocular muscles

==Lab 1==

<pubmed>22178154</pubmed>

This article reviews some important features of capacitation as well as presenting their findings regarding the role of PLD-dependent actin polymerization in sperm motility during capacitation. They demonstrated the importance of PLD-dependent actin polymerization for developing hyper-activated motility.

==Lab 2==

{|
|-
|'''Task 1'''

|-
|[[File:Paternal_chromatin_mouse_embryos.jpg|thumb|left]]

|-
|'''Task 2'''

|-
|Rac1 and RhoA are Rho GTPases that regulate the invasion of the human embryo through the endometrial stroma. Inhibition of Rac1 expression prevents embryo invasion of the stroma, whereas inhibition of RhoA promotes it. Rac1 also plays a role in human endometrial stromal cell migration.

<pubmed>PMC2562412</pubmed>
|}

==Lab 3==

1. Gestational age refers to the time period between the first day of the mothers last period and birth. Fertilisation age is the time between conception and birth. <ref><pubmed>15520122</pubmed></ref>.

==Lab 4==

1.

Amniocentesis- involves using a needle to take a sample of amnitoic fluid. It can be used to detect down syndrome and turner syndrome among other abnormalities.

Chorionic villus sampling- a needle is used to take a sample of chorionic villus (placental tissue). It is helpful in detecting down syndrome and cystic fibrosis.

2.

<pubmed>3240835</pubmed>

This paper demonstrates the successful use of intrathecally injected mesenchymal cells derived from human umbilical cord blood to partially recanalise a dissected basilar artery. The patient was a 17 year old Korean man with infarction of the bilateral pons, midbrain and right superior cerebellum as a result of the basilar artery dissection.

The paper identifies that human umbilical cord blood contains hematopoietic stem cells, as well as mesenchymal stem cells which express neural makers Tuj1, TrkA, glial fibrillary acidic protein and cyclic nucleotide phosphodiesterases.

As a result of his condition the patient became quadriplegic, was unable to speak, and was unable to move his eyes, as well as a number of other symptoms. His clinical symptoms were visibly improved 5 days after the initial treatment with the mesenchymal cells. After the 27th day of treatment he regained his gag reflex, was able to swallow, had pupil dilation and was able to move his eyes, his soft palate stopped sagging, and the rigidity of his muscle tone reduced enough to allow him to sit in a wheelchair.

==Lab 7==

1.Provide a one sentence definition of a muscle satellite cell (b) In one paragraph, briefly discuss two examples of when satellite cells are activated ?

Satelite cells are stem cells that are located under the basal laminar of each muscle. When muscle is damaged satelite cells infiltrate the muscle and repair or replace it. They are normally quiescent.

2.In one brief paragraph, describe what happens to skeletal muscle fibre type and size when the innervating motor nerve sustains long term damage such as in spinal cord injury?

==Peer Review==

'''Group 2- Somatosensory'''

-Great introduction. Really puts the project in context and justifies the importance of your research. Citations need to be formatted like the rest of the page

-History of discoveries-very poor syntax, word repetition and no paragraphs. What is Weber's full name? This is entitled "history of discoveries" when it is actually just a very brief, nonspecific summary of "Weber". What about the other interesting discoveries from various scientists over decades?

-Adult Central Somatosensory systems- ascending in what? Position? Importance? Activity? Sensitivity? This needs a more informative opening sentence.

-Trigeminal system and Development of the Primary Somatosensory Cortex- are well explained and ideas are presented in a logical, flowing manner. Great picture with a good description and referencing (impressed you drew it).

-"making connections between...." what do the stages mean? Why does it start at stage 23 instead of stage 1?

-touch/touch receptors is good but where are the references?

-pain and pressure sections also good but needs paragraphs and the formatting of citations is incorrect

-bullet points in pressure section need a brief sentence introducing their purpose. Papers listed at bottom of section should be correctly cited instead of having hyperlinks

-interesting info in temperature

-current research- maybe you could put the name of the paper and authors and explain how they conducted their study? That would help with understanding the nice picture

-Glossary is incomplete

-Needs more pictures

-minor grammatical and spelling errors throughout but overall very good and well sequenced.

'''Group 3- Taste'''

Overall this is an excellent project. Well written, great informative photos, good use of tables, and comprehensive information that's well explained.

A few of the photos don't have the appropriate copyright information and some sections of text haven't been referenced, but in general this ticks all of the boxes

'''Group 4- olfaction'''

-numerous typos and syntax errors throughout. My favourite is "naval cavity"

-generally well explained and I like how you've used different formats for each section to keep it interesting

-this seems a bit random-

"SINUSES: A:
EFFECT OF AMNIOTIC FLUID ON THE DEVELOPMENT OF OLFACTION IN THE FETUS (current research in the field):"

-I think the anatomy section should come before the developmental timeline just to put the developmental stages in context

-abnormal function is very comprehensive :)

-current research is great, it appears some quality research went into this

-excellent use of resources throughout, including your external links. I think you've covered everything well

'''Group 5- abnormal vision'''

-content of introduction is good and immediately puts the page in context. Emphasises abnormal development. Perhaps reconsider the syntax of some of the sentences

-paragraphing throughout project needs review

-a picture near the beginning would make the page more engaging. Seeing you can't talk too much about normal eye development, it might help in conveying some information

-you frequently make use of the carnergie stages, which is great, but perhaps briefly describe what this system means

-it's good that you have contrasted normal and abnormal development for each structure, but make sure the information isn't repeated in the "normal development" section, or perhaps remove that section altogether

- info about what the different genes control is good. What does "the first embryonic days 8.5" mean?

-I assume the two separate sections in "ocular manifestations" are genetic and environmental, but because they're not stated in the intro of this section and there's so much information in-between, it's difficult to tell. The formatting of this section adds to the confusion. Keeping the information and formatting consistent for each abnormality will make this easier to follow. The appropriate heading, sub-heading etc formatting needs to be used as well

-I like your case study, it reminds us of how these problems effect real people

-no current research or external links section?

-excellent use of resources

'''Group 6-Hearing'''

-you had me at puppy

-good intro (a few typos) and history (I like your table)

-the start of adult anatomy and histology should have an opening sentence instead of just listing information. There is no histology?

-I'm guessing the heading for development is meant to be bigger instead of it appearing to be part of "adult anatomy and histology"? This section is very comprehensive!

-your "neural domain" drawing is a good way of explaining this concept

-the summary box is a great idea, but perhaps it should be entitled "Summary of inner ear development"

-I don't understand why this is present- "NOTE: DEFINITIONS OF SYNDROMIC AND NON SYNDROMIC HEARING LOSS". You have explained what non-syndromic hearing loss is in the 1 Mutation of GJB2 gene section, but as your note says, it might be good to have a brief section with these definitions

-your genetic and structural disease tables are nice but I feel that the formatting should be the same for all of the diseases, or you should explain why you've chosen to emphasise these abnormalities

-the PDF in the Toxoplasmosis section seems to have some good info, but should be formatted like the other references

-the references in the rubella, cytomegalovirus infection, drugs and technologies to detect sections need to be formatted properly. Some info in drugs section isn't referenced at all

-technologies to detect is not a very informative heading, you need to specify what you're detecting. The syntax in this section and "technologies to overcome the problems" is poor (including the headings)

-in text hyperlinks in current research section are good for making page more interactive

-you appear to have used a lot of great resources

== References ==
<references/>

User:Z3254758

2012-09-25T22:58:07Z

Z3254758: /* Peer Review */

==Lab Attendance==

--[[User:Z3254758|Z3254758]] 10:04, 25 July 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:35, 1 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:09, 8 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:04, 15 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:15, 22 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:05, 29 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 11:08, 12 September 2012 (EST) arrived at 10:10am

--[[User:Z3254758|Z3254758]] 10:02, 19 September 2012 (EST)

Ciliary Body
Iris
Cornea
Aqueous Chambers
Lacrimal Glands
Extraocular muscles

==Lab 1==

<pubmed>22178154</pubmed>

This article reviews some important features of capacitation as well as presenting their findings regarding the role of PLD-dependent actin polymerization in sperm motility during capacitation. They demonstrated the importance of PLD-dependent actin polymerization for developing hyper-activated motility.

==Lab 2==

{|
|-
|'''Task 1'''

|-
|[[File:Paternal_chromatin_mouse_embryos.jpg|thumb|left]]

|-
|'''Task 2'''

|-
|Rac1 and RhoA are Rho GTPases that regulate the invasion of the human embryo through the endometrial stroma. Inhibition of Rac1 expression prevents embryo invasion of the stroma, whereas inhibition of RhoA promotes it. Rac1 also plays a role in human endometrial stromal cell migration.

<pubmed>PMC2562412</pubmed>
|}

==Lab 3==

1. Gestational age refers to the time period between the first day of the mothers last period and birth. Fertilisation age is the time between conception and birth. <ref><pubmed>15520122</pubmed></ref>.

==Lab 4==

1.

Amniocentesis- involves using a needle to take a sample of amnitoic fluid. It can be used to detect down syndrome and turner syndrome among other abnormalities.

Chorionic villus sampling- a needle is used to take a sample of chorionic villus (placental tissue). It is helpful in detecting down syndrome and cystic fibrosis.

2.

<pubmed>3240835</pubmed>

This paper demonstrates the successful use of intrathecally injected mesenchymal cells derived from human umbilical cord blood to partially recanalise a dissected basilar artery. The patient was a 17 year old Korean man with infarction of the bilateral pons, midbrain and right superior cerebellum as a result of the basilar artery dissection.

The paper identifies that human umbilical cord blood contains hematopoietic stem cells, as well as mesenchymal stem cells which express neural makers Tuj1, TrkA, glial fibrillary acidic protein and cyclic nucleotide phosphodiesterases.

As a result of his condition the patient became quadriplegic, was unable to speak, and was unable to move his eyes, as well as a number of other symptoms. His clinical symptoms were visibly improved 5 days after the initial treatment with the mesenchymal cells. After the 27th day of treatment he regained his gag reflex, was able to swallow, had pupil dilation and was able to move his eyes, his soft palate stopped sagging, and the rigidity of his muscle tone reduced enough to allow him to sit in a wheelchair.

==Lab 7==

1.Provide a one sentence definition of a muscle satellite cell (b) In one paragraph, briefly discuss two examples of when satellite cells are activated ?

Satelite cells are stem cells that are located under the basal laminar of each muscle. When muscle is damaged satelite cells infiltrate the muscle and repair or replace it. They are normally quiescent.

2.In one brief paragraph, describe what happens to skeletal muscle fibre type and size when the innervating motor nerve sustains long term damage such as in spinal cord injury?

==Peer Review==

'''Group 2- Somatosensory'''

-Great introduction. Really puts the project in context and justifies the importance of your research. Citations need to be formatted like the rest of the page

-History of discoveries-very poor syntax, word repetition and no paragraphs. What is Weber's full name? This is entitled "history of discoveries" when it is actually just a very brief, nonspecific summary of "Weber". What about the other interesting discoveries from various scientists over decades?

-Adult Central Somatosensory systems- ascending in what? Position? Importance? Activity? Sensitivity? This needs a more informative opening sentence.

-Trigeminal system and Development of the Primary Somatosensory Cortex- are well explained and ideas are presented in a logical, flowing manner. Great picture with a good description and referencing (impressed you drew it).

-"making connections between...." what do the stages mean? Why does it start at stage 23 instead of stage 1?

-touch/touch receptors is good but where are the references?

-pain and pressure sections also good but needs paragraphs and the formatting of citations is incorrect

-bullet points in pressure section need a brief sentence introducing their purpose. Papers listed at bottom of section should be correctly cited instead of having hyperlinks

-interesting info in temperature

-current research- maybe you could put the name of the paper and authors and explain how they conducted their study? That would help with understanding the nice picture

-Glossary is incomplete

-Needs more pictures

-minor grammatical and spelling errors throughout but overall very good and well sequenced.

'''Group 3- Taste'''

Overall this is an excellent project. Well written, great informative photos, good use of tables, and comprehensive information that's well explained.

A few of the photos don't have the appropriate copyright information and some sections of text haven't been referenced, but in general I think this is the best project.

'''Group 4- olfaction'''

-numerous typos and syntax errors throughout. My favourite is "naval cavity"

-generally well explained and I like how you've used different formats for each section to keep it interesting

-this seems a bit random-

"SINUSES: A:
EFFECT OF AMNIOTIC FLUID ON THE DEVELOPMENT OF OLFACTION IN THE FETUS (current research in the field):"

-I think the anatomy section should come before the developmental timeline just to put the developmental stages in context

-abnormal function is very comprehensive :)

-current research is great, it appears some quality research went into this

-excellent use of resources throughout, including your external links. I think you've covered everything well

'''Group 5- abnormal vision'''

-content of introduction is good and immediately puts the page in context. Emphasises abnormal development. Perhaps reconsider the syntax of some of the sentences

-paragraphing throughout project needs review

-a picture near the beginning would make the page more engaging. Seeing you can't talk too much about normal eye development, it might help in conveying some information

-you frequently make use of the carnergie stages, which is great, but perhaps briefly describe what this system means

-it's good that you have contrasted normal and abnormal development for each structure, but make sure the information isn't repeated in the "normal development" section, or perhaps remove that section altogether

- info about what the different genes control is good. What does "the first embryonic days 8.5" mean?

-I assume the two separate sections in "ocular manifestations" are genetic and environmental, but because they're not stated in the intro of this section and there's so much information in-between, it's difficult to tell. The formatting of this section adds to the confusion. Keeping the information and formatting consistent for each abnormality will make this easier to follow. The appropriate heading, sub-heading etc formatting needs to be used as well

-I like your case study, it reminds us of how these problems effect real people

-no current research or external links section?

-excellent use of resources

'''Group 6-Hearing'''

-you had me at puppy

-good intro (a few typos) and history (I like your table)

-the start of adult anatomy and histology should have an opening sentence instead of just listing information. There is no histology?

-I'm guessing the heading for development is meant to be bigger instead of it appearing to be part of "adult anatomy and histology"? This section is very comprehensive!

-your "neural domain" drawing is a good way of explaining this concept

-the summary box is a great idea, but perhaps it should be entitled "Summary of inner ear development"

-I don't understand why this is present- "NOTE: DEFINITIONS OF SYNDROMIC AND NON SYNDROMIC HEARING LOSS". You have explained what non-syndromic hearing loss is in the 1 Mutation of GJB2 gene section, but as your note says, it might be good to have a brief section with these definitions

-your genetic and structural disease tables are nice but I feel that the formatting should be the same for all of the diseases, or you should explain why you've chosen to emphasise these abnormalities

-the PDF in the Toxoplasmosis section seems to have some good info, but should be formatted like the other references

-the references in the rubella, cytomegalovirus infection, drugs and technologies to detect sections need to be formatted properly. Some info in drugs section isn't referenced at all

-technologies to detect is not a very informative heading, you need to specify what you're detecting. The syntax in this section and "technologies to overcome the problems" is poor (including the headings)

-in text hyperlinks in current research section are good for making page more interactive

-you appear to have used a lot of great resources

== References ==
<references/>

User:Z3254758

2012-09-25T22:27:43Z

Z3254758: /* Peer Review */

==Lab Attendance==

--[[User:Z3254758|Z3254758]] 10:04, 25 July 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:35, 1 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:09, 8 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:04, 15 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:15, 22 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:05, 29 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 11:08, 12 September 2012 (EST) arrived at 10:10am

--[[User:Z3254758|Z3254758]] 10:02, 19 September 2012 (EST)

Ciliary Body
Iris
Cornea
Aqueous Chambers
Lacrimal Glands
Extraocular muscles

==Lab 1==

<pubmed>22178154</pubmed>

This article reviews some important features of capacitation as well as presenting their findings regarding the role of PLD-dependent actin polymerization in sperm motility during capacitation. They demonstrated the importance of PLD-dependent actin polymerization for developing hyper-activated motility.

==Lab 2==

{|
|-
|'''Task 1'''

|-
|[[File:Paternal_chromatin_mouse_embryos.jpg|thumb|left]]

|-
|'''Task 2'''

|-
|Rac1 and RhoA are Rho GTPases that regulate the invasion of the human embryo through the endometrial stroma. Inhibition of Rac1 expression prevents embryo invasion of the stroma, whereas inhibition of RhoA promotes it. Rac1 also plays a role in human endometrial stromal cell migration.

<pubmed>PMC2562412</pubmed>
|}

==Lab 3==

1. Gestational age refers to the time period between the first day of the mothers last period and birth. Fertilisation age is the time between conception and birth. <ref><pubmed>15520122</pubmed></ref>.

==Lab 4==

1.

Amniocentesis- involves using a needle to take a sample of amnitoic fluid. It can be used to detect down syndrome and turner syndrome among other abnormalities.

Chorionic villus sampling- a needle is used to take a sample of chorionic villus (placental tissue). It is helpful in detecting down syndrome and cystic fibrosis.

2.

<pubmed>3240835</pubmed>

This paper demonstrates the successful use of intrathecally injected mesenchymal cells derived from human umbilical cord blood to partially recanalise a dissected basilar artery. The patient was a 17 year old Korean man with infarction of the bilateral pons, midbrain and right superior cerebellum as a result of the basilar artery dissection.

The paper identifies that human umbilical cord blood contains hematopoietic stem cells, as well as mesenchymal stem cells which express neural makers Tuj1, TrkA, glial fibrillary acidic protein and cyclic nucleotide phosphodiesterases.

As a result of his condition the patient became quadriplegic, was unable to speak, and was unable to move his eyes, as well as a number of other symptoms. His clinical symptoms were visibly improved 5 days after the initial treatment with the mesenchymal cells. After the 27th day of treatment he regained his gag reflex, was able to swallow, had pupil dilation and was able to move his eyes, his soft palate stopped sagging, and the rigidity of his muscle tone reduced enough to allow him to sit in a wheelchair.

==Lab 7==

1.Provide a one sentence definition of a muscle satellite cell (b) In one paragraph, briefly discuss two examples of when satellite cells are activated ?

Satelite cells are stem cells that are located under the basal laminar of each muscle. When muscle is damaged satelite cells infiltrate the muscle and repair or replace it. They are normally quiescent.

2.In one brief paragraph, describe what happens to skeletal muscle fibre type and size when the innervating motor nerve sustains long term damage such as in spinal cord injury?

==Peer Review==

'''Group 2- Somatosensory'''

-Great introduction. Really puts the project in context and justifies the importance of your research. Citations need to be formatted like the rest of the page

-History of discoveries-very poor syntax, word repetition and no paragraphs. What is Weber's full name? This is entitled "history of discoveries" when it is actually just a very brief, nonspecific summary of "Weber". What about the other interesting discoveries from various scientists over decades?

-Adult Central Somatosensory systems- ascending in what? Position? Importance? Activity? Sensitivity? This needs a more informative opening sentence.

-Trigeminal system and Development of the Primary Somatosensory Cortex- are well explained and ideas are presented in a logical, flowing manner. Great picture with a good description and referencing (impressed you drew it).

-what do the stages mean? Why does it start at stage 23 instead of stage 1?

-touch/touch receptors is good but where are the references?

-pain and pressure sections also good but needs paragraphs and the formatting of citations is incorrect

-bullet points in pressure section need a brief sentence introducing their purpose. Papers listed at bottom of section should be correctly cited instead of having hyperlinks

-interesting info in temperature

-current research- maybe you could put the name of the paper and authors and explain how they conducted their study? That would help with understanding the nice picture

-Glossary is incomplete

-Needs more pictures

-minor grammatical and spelling errors throughout but overall very good and well sequenced.

'''Group 3- Taste'''

-Overall this is an excellent project. Well written, great informative photos, good use of tables, and comprehensive information that's well explained.

-A few of the photos don't have the appropriate copyright information and some sections of text haven't been referenced, but in general it ticks all of the boxes

'''Group 4- olfaction'''

-numerous typos and syntax errors throughout. My favourite is "naval cavity"

-generally well explained and I like how you've used different formats for each section to keep it interesting

-this seems a bit random-

"SINUSES: A:
EFFECT OF AMNIOTIC FLUID ON THE DEVELOPMENT OF OLFACTION IN THE FETUS (current research in the field):"

-I think the anatomy section should come before the developmental timeline just to put the developmental stages in context

-abnormal function is very comprehensive :)

-current research is great, it appears some quality research went into this

-excellent use of resources throughout, including your external links. I think you've covered everything well

'''Group 5- abnormal vision'''

-content of introduction is good and immediately puts the page in context. Emphasises abnormal development. Perhaps reconsider the syntax of some of the sentences

-paragraphing throughout project needs review

-a picture near the beginning would make the page more engaging. Seeing you can't talk too much about normal eye development, it might help in conveying some information

-you frequently make use of the carnergie stages, which is great, but perhaps briefly describe what this system means

-it's good that you have contrasted normal and abnormal development for each structure, but make sure the information isn't repeated in the "normal development" section, or perhaps remove that section altogether

- info about what the different genes control is good. What does "the first embryonic days 8.5" mean?

-I assume the two separate sections in "ocular manifestations" are genetic and environmental, but because they're not stated in the intro of this section and there's so much information in-between, it's difficult to tell. The formatting of this section adds to the confusion. Keeping the information and formatting consistent for each abnormality will make this easier to follow. The appropriate heading, sub-heading etc formatting needs to be used as well

-I like your case study, it reminds us of how these problems effect real people

-no current research or external links section?

-excellent use of resources

'''Group 6-Hearing'''

-you had me at puppy

-good intro (a few typos) and history (I like your table)

-the start of adult anatomy and histology should have an opening sentence instead of just listing information. There is no histology?

-I'm guessing the heading for development is meant to be bigger instead of it appearing to be part of "adult anatomy and histology"? This section is very comprehensive!

-your "neural domain" drawing is a good way of explaining this concept

-the summary box is a great idea, but perhaps it should be entitled "Summary of inner ear development"

-I don't understand why this is present- "NOTE: DEFINITIONS OF SYNDROMIC AND NON SYNDROMIC HEARING LOSS". You have explained what non-syndromic hearing loss is in the 1 Mutation of GJB2 gene section, but as your note says, it might be good to have a brief section with these definitions

-your genetic and structural disease tables are nice but I feel that the formatting should be the same for all of the diseases, or you should explain why you've chosen to emphasise these abnormalities

-the PDF in the Toxoplasmosis section seems to have some good info, but should be formatted like the other references

-the references in the rubella, cytomegalovirus infection, drugs and technologies to detect sections need to be formatted properly. Some info in drugs section isn't referenced at all

-technologies to detect is not a very informative heading, you need to specify what you're detecting. The syntax in this section and "technologies to overcome the problems" is poor (including the headings)

-in text hyperlinks in current research section are good for making page more interactive

-you appear to have used a lot of great resources

== References ==
<references/>

User:Z3254758

2012-09-25T22:19:25Z

Z3254758: /* Lab 7 */

==Lab Attendance==

--[[User:Z3254758|Z3254758]] 10:04, 25 July 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:35, 1 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:09, 8 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:04, 15 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:15, 22 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 10:05, 29 August 2012 (EST)

--[[User:Z3254758|Z3254758]] 11:08, 12 September 2012 (EST) arrived at 10:10am

--[[User:Z3254758|Z3254758]] 10:02, 19 September 2012 (EST)

Ciliary Body
Iris
Cornea
Aqueous Chambers
Lacrimal Glands
Extraocular muscles

==Lab 1==

<pubmed>22178154</pubmed>

This article reviews some important features of capacitation as well as presenting their findings regarding the role of PLD-dependent actin polymerization in sperm motility during capacitation. They demonstrated the importance of PLD-dependent actin polymerization for developing hyper-activated motility.

==Lab 2==

{|
|-
|'''Task 1'''

|-
|[[File:Paternal_chromatin_mouse_embryos.jpg|thumb|left]]

|-
|'''Task 2'''

|-
|Rac1 and RhoA are Rho GTPases that regulate the invasion of the human embryo through the endometrial stroma. Inhibition of Rac1 expression prevents embryo invasion of the stroma, whereas inhibition of RhoA promotes it. Rac1 also plays a role in human endometrial stromal cell migration.

<pubmed>PMC2562412</pubmed>
|}

==Lab 3==

1. Gestational age refers to the time period between the first day of the mothers last period and birth. Fertilisation age is the time between conception and birth. <ref><pubmed>15520122</pubmed></ref>.

==Lab 4==

1.

Amniocentesis- involves using a needle to take a sample of amnitoic fluid. It can be used to detect down syndrome and turner syndrome among other abnormalities.

Chorionic villus sampling- a needle is used to take a sample of chorionic villus (placental tissue). It is helpful in detecting down syndrome and cystic fibrosis.

2.

<pubmed>3240835</pubmed>

This paper demonstrates the successful use of intrathecally injected mesenchymal cells derived from human umbilical cord blood to partially recanalise a dissected basilar artery. The patient was a 17 year old Korean man with infarction of the bilateral pons, midbrain and right superior cerebellum as a result of the basilar artery dissection.

The paper identifies that human umbilical cord blood contains hematopoietic stem cells, as well as mesenchymal stem cells which express neural makers Tuj1, TrkA, glial fibrillary acidic protein and cyclic nucleotide phosphodiesterases.

As a result of his condition the patient became quadriplegic, was unable to speak, and was unable to move his eyes, as well as a number of other symptoms. His clinical symptoms were visibly improved 5 days after the initial treatment with the mesenchymal cells. After the 27th day of treatment he regained his gag reflex, was able to swallow, had pupil dilation and was able to move his eyes, his soft palate stopped sagging, and the rigidity of his muscle tone reduced enough to allow him to sit in a wheelchair.

==Lab 7==

1.Provide a one sentence definition of a muscle satellite cell (b) In one paragraph, briefly discuss two examples of when satellite cells are activated ?

Satelite cells are stem cells that are located under the basal laminar of each muscle. When muscle is damaged satelite cells infiltrate the muscle and repair or replace it. They are normally quiescent.

2.In one brief paragraph, describe what happens to skeletal muscle fibre type and size when the innervating motor nerve sustains long term damage such as in spinal cord injury?

==Peer Review==

'''Group 2- Somatosensory'''
-Great introduction. Really puts the project in context and justifies the importance of your research. Citations need to be formatted like the rest of the page

-History of discoveries-very poor syntax, word repetition and no paragraphs. What is Weber's full name? This is entitled "history of discoveries" when it is actually just a very brief, nonspecific summary of "Weber". What about the other interesting discoveries from various scientists over decades?

-Adult Central Somatosensory systems- ascending in what? Position? Importance? Activity? Sensitivity? This needs a more informative opening sentence.

-Trigeminal system and Development of the Primary Somatosensory Cortex- are well explained and ideas are presented in a logical, flowing manner. Great picture with a good description and referencing (impressed you drew it).

-making connections between.... - what do the stages mean? Why does it start at stage 23 instead of stage 1?

-touch/touch receptors is good but where are the references?

-pain and pressure sections also good but needs paragraphs and the formatting of citations is incorrect

-bullet points in pressure section need a brief sentence introducing their purpose. Papers listed at bottom of section should be correctly cited instead of having hyperlinks

-interesting info in temperature

-current research- maybe you could put the name of the paper and authors and explain how they conducted their study? That would help with understanding the nice picture

-Glossary is incomplete

-Needs more pictures

-minor grammatical and spelling errors throughout but overall very good and well sequenced.

'''Group 3- Taste'''

-Overall this is an excellent project. Well written, great informative photos, good use of tables, and comprehensive information that's well explained.

-A few of the photos don't have the appropriate copyright information and some sections of text haven't been referenced, but in general it ticks all of the boxes

'''Group 4- olfaction'''

-numerous typos and syntax errors throughout. My favourite is "naval cavity"

-generally well explained and I like how you've used different formats for each section to keep it interesting

-this seems a bit random-

"SINUSES: A:
EFFECT OF AMNIOTIC FLUID ON THE DEVELOPMENT OF OLFACTION IN THE FETUS (current research in the field):"

-I think the anatomy section should come before the developmental timeline just to put the developmental stages in context

-abnormal function is very comprehensive :)

-current research is great, it appears some quality research went into this

-excellent use of resources throughout, including your external links. I think you've covered everything well

'''Group 5- abnormal vision'''

-content of introduction is good and immediately puts the page in context. Emphasises abnormal development. Perhaps reconsider the syntax of some of the sentences

-paragraphing throughout project needs review

-a picture near the beginning would make the page more engaging. Seeing you can't talk too much about normal eye development, it might help in conveying some information

-you frequently make use of the carnergie stages, which is great, but perhaps briefly describe what this system means

-it's good that you have contrasted normal and abnormal development for each structure, but make sure the information isn't repeated in the "normal development" section, or perhaps remove that section altogether

- info about what the different genes control is good. What does "the first embryonic days 8.5" mean?

-I assume the two separate sections in "ocular manifestations" are genetic and environmental, but because they're not stated in the intro of this section and there's so much information in-between, it's difficult to tell. The formatting of this section adds to the confusion. Keeping the information and formatting consistent for each abnormality will make this easier to follow. The appropriate heading, sub-heading etc formatting needs to be used as well

-I like your case study, it reminds us of how these problems effect real people

-no current research or external links section?

-excellent use of resources

'''Group 6-Hearing'''

-you had me at puppy

-good intro (a few typos) and history (I like your table)

-the start of adult anatomy and histology should have an opening sentence instead of just listing information. There is no histology?

-I'm guessing the heading for development is meant to be bigger instead of it appearing to be part of "adult anatomy and histology"? This section is very comprehensive!

-your "neural domain" drawing is a good way of explaining this concept

-the summary box is a great idea, but perhaps it should be entitled "Summary of inner ear development"

-I don't understand why this is present- "NOTE: DEFINITIONS OF SYNDROMIC AND NON SYNDROMIC HEARING LOSS". You have explained what non-syndromic hearing loss is in the 1 Mutation of GJB2 gene section, but as your note says, it might be good to have a brief section with these definitions

-your genetic and structural disease tables are nice but I feel that the formatting should be the same for all of the diseases, or you should explain why you've chosen to emphasise these abnormalities

-the PDF in the Toxoplasmosis section seems to have some good info, but should be formatted like the other references

-the references in the rubella, cytomegalovirus infection, drugs and technologies to detect sections need to be formatted properly. Some info in drugs section isn't referenced at all

-technologies to detect is not a very informative heading, you need to specify what you're detecting. The syntax in this section and "technologies to overcome the problems" is poor (including the headings)

-in text hyperlinks in current research section are good for making page more interactive

-you appear to have used a lot of great resources

== References ==
<references/>

Talk:2012 Group Project 6

2012-09-25T12:05:16Z

Z3254758: /* Student evaluations */

{{2012GroupDiscussion}}

This is a recent review on hearing. http://jcb.rupress.org/content/190/1/9.full JCB content allows reuse.

=Student evaluations=

'''Please use this space to post your Group 6 student evaluation'''

Really funny image of the large eared dog is a great way to capture reader attention. It’s nice to see the importance of hearing in so many aspects of our lives. Finishing the introduction with an outline of the project is very appropriate because it sets up a framework of what you are going to talk about Overall, the introduction was very well written. The language is beautiful. However, there is a typo in ‘energy produced has be converted’.

Information presented in the history table was succinct and brief. It would be good to include proper references (in text citations) for each entry. There seems to be a gap between 1898 and 1978. Have there been any discoveries in those 80 years? It just seems like a big leap to go from the first portable electric hearing aid to a cochlear implant without any advances in hearing aid technology in between those years.

Anatomy of the ear was very clear. The text related to the picture nicely. The image enables readers to see all parts of the ear in relation to each other. It would nice to put an enlarged image of the inner ear and organ of Corti. Some people might not know what a ‘utricle’ or ‘saccule’ looks like and on that image it may be too hard to see.

With the development section, it would be good to include some images related to the development of outer, middle and inner ear. For example, include an image of week 5 embryo and label where the pharyngeal arches are so people with no background in embryology can understand what parts of the embryo you are referring to. Some of terminology, such as ‘auricular enlargement’, ‘tragus’ and ‘helix’, is hard to understand. Relevant images would help.

It would be good to put in text citations after important sentences in the paragraphs of outer, inner and middle ear development. This is because a couple of paragraphs (e.g. the middle ear paragraph) had several citations at the end of the paragraph and we don’t know which sentence or fact corresponds to which citation.

In the ‘Otic placode’ section, it’s great to see the images well referenced and have the correct copyright. ‘Early expression of Pax2 and Pax8 compared’ and ‘The expression of Sox2 and Sox3 during development of the ear’ images were useful because they reflected the processes outlined in the text. Maybe simplify the signalling information on the FGFs because I found it hard to understand. Maybe give a summary of the roles of the major factors – a table, showing ‘factor...process it controls’, would be nice.

‘Recent model related to sensory fate’ image made a complex process simple – this is great to see. ‘Establishing polarity and formation of inner ear structures’ section was very well written. Maybe put this under the same section as the inner ear. I feel the 2 sections are related.

Abnormal hearing section was very detailed and extensive. It covered so many hearing abnormalities. It would be good to include available treatments for some of the diseases and give a summary table – ‘causes...disease...description of disease...prevalence...treatments’.
--[[User:Z3332863|Z3332863]] 14:34, 25 September 2012 (EST)

----

"The humorous image at the beginning accompanied by the “CAN YOU HEAR ME” in the introduction was a very clever way of drawing the reader in and making your message loud and clear, with all pun intended. Great work! I like how you also clearly introduced what your page will discuss.

No issues with the history timeline – it is well set out and very clear and concise. The section of the Adult Anatomy is quite clear also, however you refer to histology in the title – perhaps include an image that shows the histology of a certain structure. In regards to the section on Development, it is very clear that a lot of work has gone into this. However, be aware that you must reference all your information to avoid being penalised or accused of plagiarism. Additionally, images would help your explanations – it is slightly word dense at the moment so perhaps arrange some of the content into dot points in order to engage your reader. The sections on the Otic Placode and Otocyst are great examples of webpage layout, with the dot points and a clear image which links to the content. I especially liked how a summary of the inner ear was included – this demonstrates an awareness of peer teaching and reiterates your key points. Excellent!

The section on abnormal hearing was a joy to read and was cleverly set out in tables – the information will be even more enhanced by the images I can see you have indicated you will add. I also liked how you divided the different congenital abnormalities into environmental and genetic. In order to enhance these sections, incorporate some dot points or a diagram showing how viruses/drugs can cross the placenta.

The “Technologies to Detect” would best be organised under subheadings – at present it is a little daunting to read in the paragraph-paragraph format which is a shame because the information is very interesting! Also, be aware of correct referencing formats which you can find on the tutorial page – your in text references should be numbers and the references should go at the end of the webpage. I liked the “Technologies to overcome the problems” – may I suggest including images or diagrams of these technologies?

It would be great to see more examples of Current Research. However, what you have presented thus far is great – you have clearly described the aims and findings of research.

Overall, good work – just make sure you are consistent with referencing and strike a balance between images and text."

------
What drew me into reading this page, was the humerous image at the beginning together with the perfect introduction that encourages people to read on. The sub-headings, headings, figures and tables make it really simple for the reader to take in all the key points of the research area. I particularly like the inclusion of technologies to detect abnormalities. However, this great balance is not met in the development section where there is too much text and not enough images or diagrams to guide the thinking. I would suggest trying to simplify the information into key points by eliminating any information that would not necessarily contribute to a sound understanding of the topic. This could possibly be achieved further by having a separation or different sub-heading for the description of the development process and the description of the cellular structure.

What stands out the most about this page, is the amount of research you have put in to the genetics and molecular processes of development and abnormalities. Whilst it is very interesting and shows the amount of time you've put into having a clear understanding, at times it seems the naming of genes and their proteins do not contribute to a sound understanding but rather adds confusion. For example, your reference to FGF and Sox are important but you have further included the different types of FGF and Sox proteins without offering much of an explanation about what distinguishes them from eachother. Generalising in these cases (to just FGF not FGF1,2,3..) would not limit the extent to which a student may learn from your information but will avoid any confusion.

Another way you could further improve the page is with the inclusion of student-drawn images or learning aids to accompany the text. This way you can avoid the inclusion of unnecessary information on borrowed images, for example, the wild-type inner ear morphology image. The referencing system is consistent and well set-out on the page and the long list of references and interesting discoveries is impressive. Overall I would just encourage condensing the information into dot points that help simplify the reader’s understanding.

Good luck!

-----

Good use of image, it attracts my attention straight away and it is very relaxing to look at a funny image before reading the text. Introduction is precise and to point, clearly identifying the purpose of the project and gives a general overview of what the readers will see or learn from the project. The timeline for history is good, but maybe indicate what kind of history is it? The adult anatomy and histology section is good but the heading should be "adult ear anatomy and histology"? I like it how the ear is divided into outer ear, middle ear and inner ear and then it is further divided into components that are included in these 3 different parts of the ear. This makes the structure of the ear very easy to understand and we can locate the different structure of the ear much easily. The image used in this section is very good with clearly labelled structures, the image also contained all the important information and referenced correctly but you forgot to include the student image template.

The development section is well-researched and contain a lot of information. More images should be put in to balance out the heavy text load in the section but the information provided is very in-depth and precise. The developmental process is explained in simple terms but i noticed that there is an imbalance in terms of research and information between middle ear and the other two. Maybe more research should be done on the middle ear. The summary of the inner idea was a good idea because it clearly points out the main points that readers should know, should consider do something similar for both the outer and middle ear.

The abnormal hearing section is well-researched and interesting. It is very nice to know about the association between gene mutation and its influence on hearing development. Maybe some images should be put here to balance out the text a bit. The table of genetic syndrome is very nice, maybe you can consider putting the gene mutations into table as well. The environmental section is nice and well-researched but maybe images should be put here because right now it is pretty boring just going through all the text. And there are just some weird reference under each infections but i think this can be fixed soon. Structural malformation of the ear table is nice as well, clearly showing all the important information. It will look even better when all the images are put in.

Overall, i thought the project is really good. Contained a lot of useful information and a lot of research effort has been put in, all the information are related to the research topic. The tables work really well and the structure of the page is easy to follow. Referencing is generally good but maybe get rid of some of the random citations in sections. More images should be put in to balance out the heavy text but I thought it was a very well-researched project. Hope this helps :)

----

Group Assessment Criteria:
# ''The key points relating to the topic that your group was allocated are clearly described.'' The introduction clearly outlines the key points of the project and the content is well described in the text.
# ''The choice of content, headings and sub-headings, diagrams, tables, graphs show a good understanding of the topic area.'' The choice of content and headings shows a good depth of research and understanding of the topic area. The ‘Summary of the inner ear’ table was a good idea and ties in all the information nicely.
# ''Content is correctly cited and referenced.'' There are large paragraphs of texts that have no references. The images provided display the copyright notices and explanations.
# ''The wiki has an element of teaching at a peer level using the student’s own innovative diagrams, tables or figures and/or using interesting examples or explanations.'' The introduction is well written and catches the readers interest and attention. Most of the normal development section is easy to understand, however the abnormalities section is difficult to understand due to the scientific jargon. Some hand-drawn images and tables would be beneficial in order to reduce the large paragraphs of text.
# ''Evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities.'' The amount of information provided is evidence of the significant research that went into this project, and the sections such as ‘Technologies to overcome the problems’ shows research that goes ‘beyond the formal teaching activities’.
# ''Relates the topics and content of the Wiki entry to learning aims of embryology.'' The topics and content are well related to the learning aims of embryology
# ''The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic and covered the key areas necessary to inform your peers in their learning.'' All the content is relevant to the key areas of the development of the eye and demonstrates an extensive amount of research into the topic.

Additional points:
* The amount of text is overwhelming. You should make better use of tables, figures and diagrams to breakup/replace the text.
* Adult anatomy and histology: no reference to histology. Would be beneficial to have a brief explanation of the functions of each structure.
* Overall impression: Very well researched topic and I'm sure the use of tables, pictures and diagrams will make it more appealing to read!

----

The introductory image at the top of the page is very good but the "can you hear me' bit was overkill for me - maybe consider revising that. Also the small spelling mistake at the start of the introduction (should be senses not sense) is quite off-putting and should be fixed. Otherwise a good introduction.

The history timeline is very good and serves as another good introduction to the topic. Some external links are missing here though.

For development there is a lot of information in the outer ear section but not much in the middle and inner sections - it looks imbalanced and may be improved by adding to the other sections or perhaps splitting up the sections differently. Other than this the development section is very good with a lot of well researched information. The images are also good but don't forget to add the "student template". The inclusion of the summary box is a very good idea and is a good feature of the page.

The abnormal section is also very good and well researched. The subheadings are used effectively and the tables are a good addition. Adding images in the tables as well as the text will help to break up the text and promote interest.

The technology sections are an interesting addition however could be improved by referencing using the wiki system rather than standard in-text citations.

A good start has been made in the current research section however if possible add more current topics of research.

The glossary is very good and the references are extensive however don't forget to add to the external links.

----
Firstly the use of humour in this page is brilliant! Makes for an interesting and engaging read. The use of photographs and figures are particularly useful to help understand the topic but don't forget that the student template notice needs to be added to each photograph/diagram that you include. The referencing is great and extensive, perhaps though it might be an idea to see what is going on with reference number 56. The general layout of the page is really attractive too with a good balance of images and text, tables and especially the colourful Summary box. The content seems to address the course aims and requirements.

The introductory paragraph is to the point, well written and engaging. Similarly the structure and content included in the historic section is detailed and easy to read due to the table layout. The section about the development of the inner is well written but is somewhat overwhelming to look at just because of the amount of text. Maybe this could be combated by separating it into a few more paragraphs. The inclusion of genetic information in this area is great. The information under the subheading "The Otic Placode" onwards is particularly well done.

I like how the section on abnormalities is set out. However one problem with the area is the NOTE just before the table of genetic syndromes, I don't understand its purpose. Similarly the link in Goldenhar Syndrome entry appears random in comparison to the remainder of the entries.
Perhaps some more images in the abnormality section would be beneficial in breaking up the text. The paragraph discussing Rubella has two sentences in brackets at the bottom. Not sure why they are there either. If possible make "Infections" and "Drugs" into subheadings. I assume that information is still forthcoming for the section on Isotretinoin.

"Technologies to detect" is a good entry but perhaps consider changing subheading title as it is a little vague and incomplete. Also with this section there are loose references which should be included in the reference list at the bottom of the page rather than in the middle of the text. The information on hearing technology is brief but to the point. Again with the section on current research it may be an idea to include subheadings rather than bullet points, just so it is more easily accessed from the contents box at the top of the page.
Hope this helped.

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The introduction gives a good overview of the project and serves its purpose well. In addition, the technology section is another thing that stands out in this page along with the glossary and extensive referencing. These sections don't need to be worked on, but rather concentrate on expanding the page and adding a few more subheadings including headings of "current treatment" and "infection".

Information is very easy to follow due to the right choice of subheadings, tables and graphs. A few more tables and images with labels would make the information even easier to understand. Sometimes the amount of information becomes overwhelming, therefore try to break up the amount of texts by adding diagrams in between. Student hand drawn diagrams would be an excellent tool to employ as they can go well with the information provided.

The division of information between inner/middle/outer ear makes the structure easy to follow. This is a very good idea and an example as to how to break up the rest of the information which is all crammed together.
The citation and referencing seems to be correct, however, there are a number of paragraphs without any references, this is something that needs to be looked into. However, the level referencing at the end is great.

Also, there does not seem to be enough links. A few external links will benefit the page and allow readers to interact a fraction more.
Overall the page is very informative, however, altering the outlay and including a few diagrams, labeled images and external links would make the information easier to apprehend.

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Overall this is a well written page and is thoroughly researched.
While your introduction is small it is to the point. It gives an overview of hearing, its importance and outlines what your page is going to discuss.

The adult anatomy and histology part is confusing, I assume the adjacent image is related to the section and that development is a separate section. If that is so maybe the ear image should be thumb nailed or made smaller so that development looks like its own part.

Some images for development would be a nice addition to the well-researched information. While the class understands what it means others searching this page will have no point of reference as to what pharyngeal arches are for example, this is only a minor problem though.

The format of your development section is slightly confusing. Maybe by adding a line under inner and outer ear it would define it as a section on the respective area of development. I do like the summary of inner ear development at the end.

Technologies to detect, could possibly be name detection technologies/techniques has in text citations, I don’t think that these are necessary for this type of assignment.
--[[User:Z3220343|Z3220343]] 21:34, 25 September 2012 (EST)

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Group 6-Hearing

-you had me at puppy

-good intro (a few typos) and history (I like your table)

-the start of adult anatomy and histology should have an opening sentence instead of just listing information. There is no histology?

-I'm guessing the heading for development is meant to be bigger instead of it appearing to be part of "adult anatomy and histology"? This section is very comprehensive!

-your "neural domain" drawing is a good way of explaining this concept

-the summary box is a great idea, but perhaps it should be entitled "Summary of inner ear development"

-I don't understand why this is present- "NOTE: DEFINITIONS OF SYNDROMIC AND NON SYNDROMIC HEARING LOSS". You have explained what non-syndromic hearing loss is in the 1 Mutation of GJB2 gene section, but as your note says, it might be good to have a brief section with these definitions

-your genetic and structural disease tables are nice but I feel that the formatting should be the same for all of the diseases, or you should explain why you've chosen to emphasise these abnormalities

-the PDF in the Toxoplasmosis section seems to have some good info, but should be formatted like the other references

-the references in the rubella, cytomegalovirus infection, drugs and technologies to detect sections need to be formatted properly. Some info in drugs section isn't referenced at all

-technologies to detect is not a very informative heading, you need to specify what you're detecting. The syntax in this section and "technologies to overcome the problems" is poor (including the headings)

-in text hyperlinks in current research section are good for making page more interactive

-you appear to have used a lot of great resources

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=Hearing=

Normal and Abnormal

==Discussion Topics==

===Introduction===
Not what hearing is but what we are going to talk about

Image for hearing <pubmed>20624897</pubmed>
===History===

Research Contribution

==== Bartolomeo Eustachi 1514–1574 ====
Proposed that the tympanic membrane was connected to the nasopharynx was in the book ''De Auditus Organis'' in 1563. This was focusing on the the middle ear. His knowledge had allowed him to rediscover the tube found many years before and describe it correctly. This tube, the eustachian tube was named after him, by Antonio Maria Valsava and was shown in his book ''De aure humana tractatus''. <ref name="/PMC1142106"/> [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1142106 De aure humana tractatus.]

==== Antonio Maria Valsava 1666-1723 ====
The pioneer in the anatomy of the ear, published his first book ''De aure humana tractatus'' in 1704 this was the first to show and clearly describe the ear. He had been able to describe the anatomy and physiology of the ear by dissecting over thousands of corpses. He was able to separate the ear into its divisional compartments of inner, middle and outer ear.

===Adult Anatomy and Histology===

<pubmed> 15495168 </pubmed>

<pubmed> 16015653 </pubmed>

<pubmed> 9433684 </pubmed>

===Development===

<pubmed> 6650859 </pubmed>
====Outer Ear====

Historic paper

<pubmed> 17104502 </pubmed>

<pubmed> 22296782 </pubmed>

<pubmed> 12874121 </pubmed>

====Middle Ear====

<pubmed> 18803631 </pubmed>

<pubmed> 21196256 </pubmed>

<pubmed> 14973294 </pubmed>

<pubmed> 11237469 </pubmed>

<pubmed> 16600992 </pubmed>

====Inner Ear====

(can include balance organs as well)
cochlea and semi circular canals and the physiological function - how hearing works

Some papers to start with:

<pubmed>15319325</pubmed>

<pubmed>17891709</pubmed>

<pubmed>10887092</pubmed>

<pubmed>19247974</pubmed>

===Abnormal Hearing===

Just putting my articles in here so I can refer to them at a later date - will change the referencing when I have structured my points better

- DISCUSS CONDUCTIVE AND SNESORINEURAL HEARING LOSS
- ADD PICTURES OF GENETIC TRANSFER
- ADD PICTURE OF LOCATION OF GENE GJB2

Genetic defects:

1. [http://ghr.nlm.nih.gov/gene/GJB2| GJB2 Gene] (accounting for 50% of non syndromic hearing loss)

Environmental

1. Drugs:
Hearing, Speech, Language, and Vestibular Disorders in the Fetal Alcohol Syndrome: A Literature Review. Michael W. Church and James A. Kaltenbach, Alcoholism: Clinical and experimental review. Vol. 21, No. 3, May 1997 [http://www.ncbi.nlm.nih.gov/pubmed/9161611| PMID: 9161611]

2. Infections:
Congenital Rubella Deafness: A preventable disease. C. S Peckham, J. M Martin, W. C Marshall, J. A Dudgeon, The Lancet, February 3, 1979 [http://www.ncbi.nlm.nih.gov/pubmed/84910| PMID: 84910]

[http://www.ncbi.nlm.nih.gov/books/NBK1434/ |Deafness and Hereditary Hearing Loss Overview]

Etiological diagnosis in the hearing impaired newborn: Proposal of a flow chart. De Leenheer, E.M.R. ; Janssens, S. ; Padalko, E. ; Loose, D. ; Leroy, B.P. ; Dhooge, I.J. International Journal of Pediatric Otorhinolaryngology, 2011, Vol.75(1), pp.27-32

[http://sirius.library.unsw.edu.au:9003/sfx_local?frbrVersion=3&ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2012-08-26T10%3A07%3A34IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-sciversesciencedirect_elsevier&rft_val_fmt=info:ofi/fmt:kev:mtx:&rft.genre=article&rft.atitle=Congenital%20cytomegalovirus%20(CMV)%20infection%20as%20a%20cause%20of%20permanent%20bilateral%20hearing%20loss:%20A%20quantitative%20assessment&rft.jtitle=Journal%20of%20Clinical%20Virology&rft.btitle=&rft.aulast=Grosse&rft.auinit=&rft.auinit1=&rft.auinitm=&rft.ausuffix=&rft.au=Grosse%2C%20Scott%20D.&rft.aucorp=&rft.date=2008&rft.volume=41&rft.issue=2&rft.part=&rft.quarter=&rft.ssn=&rft.spage=57&rft.epage=62&rft.pages=57-62&rft.artnum=&rft.issn=1386-6532&rft.eissn=&rft.isbn=&rft.sici=&rft.coden=&rft_id=info:doi/10.1016/j.jcv.2007.09.004&rft.object_id=&svc_val_fmt=info:ofi/fmt:kev:mtx:sch_svc&svc.fulltext=yes&rft_dat=%3Csciversesciencedirect_elsevier%3ES1386-6532(07)00336-8%3C/sciversesciencedirect_elsevier%3E&rft.eisbn=&rft_id=info:oai/%3E| Congenital cytomegalovirus] (CMV) infection as a cause of permanent bilateral hearing loss: A quantitative assessment. Journal of clinical virology [1386-6532] Grosse, Scott yr:2008 vol:41 iss:2 pg:57 -62

Congenital Infections. JF Bale. Neurol Clin. 2002 Nov;20(4):1039-60, vii. [http://www.ncbi.nlm.nih.gov/pubmed/12616680| PMID: 12616680]

Related to both middle and inner ear (so we can link the technologies to this)

===Technologies to detect===
Any technologies (like pre-testing) that identify any problems with hearing development

===Technologies to overcome the problems===
(hearing aids, cochlear transplants, etc)

===Current Research===

===Glossary===

===References===

------------------------------

Allocated subheadings

J: adult anatomy, outer and middle ear development

M: Inner ear

P: History and Technologies

B: Abnormal Hearing

-------------

==Our Thoughts - put new comment at the top please==

Hey all! We are starting to get some really good and useful feedback :) Hope everyone is ready to get stuck into editing from tomorrow onwards, cause the project is DUE WED 03/10/2012 - WHICH IS NEXT WEEK!! Keep this in mind. From what I read so far, the aim will be the simplify/reduce our text and include more images. Referencing needs to be fixed as well for some parts of the project.. but all in all its quite good :) M. --[[User:Z3333865|Z3333865]] 09:03, 25 September 2012 (EST)
---------------

Hey! To everyone who is working on the history, please add this to the table! I'm about to change it now so that there is simply one table with significant dates and explanations. And it would be good if we can quickly meet up after one of the lectures tomorrow :) anyone who can't make it, please let the others know. M --[[User:Z3333865|Z3333865]] 14:31, 17 September 2012 (EST)

---------------

Hi P,
How are you going with your research? We really need to have it complete by this weeks lab so that we can spend the next couple of weeks adjusting the information. Thanks, B --[[User:Z3292017|Z3292017]] 12:08, 17 September 2012 (EST)

-------------

Hey M,

Yeah summary sounds like a good idea and maybe wiht some bolded words etc? Ive created 2 tables where I will briefly summarise the remaining diseases such as structural and genetic syndromes as my section will be too long and more boring than what it already is if I keep going. Yes, I think by our next lab would be a good idea. B. --[[User:Z3292017|Z3292017]] 19:22, 15 September 2012 (EST)

-----------

Hey B and others,

My section is almost finished. I mainly have to focus on the images. I was also thinking of putting a summary box in my section, because there is just so much text! About the due date.. I think it will be good for us all to have most of the research and text done by lab 8 (19/09/12). We can then focus on the layout and images and tables, etc. What do you think? M. --[[User:Z3333865|Z3333865]] 17:57, 15 September 2012 (EST)

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Hey guys,
I have been updating all of my abnormalities and along with the references, it will all be completed by Sunday night, exempt all the photos as that will be my final research. Thought I would update you all so we can get a finish timeframe in mind!
B. --[[User:Z3292017|Z3292017]] 15:08, 15 September 2012 (EST)
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Hi P,
In regards the technologies, you should take a look at my section, because the technologies should really be perhaps how abornal hearing can be detected in the womb (such as amniocentesis for Rubella) and also the different insstruments used for hearing and why they do and don't work on certain patients. and perhaps with the history go a bit more indept/ greater explanation. such as if the first hearing aid was developed, find a picture and say what they originiall used to create noise for the patient etc. Use bulletpoints if you don't want it to seem too full on Do you guys agree?
B. --[[User:Z3292017|Z3292017]] 15:02, 15 September 2012 (EST)
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Hey P.
The history section should contain major discoveries and the person(s) of interest. I started writing things down in a table. If anyone find info they should put that in and the original document/article should be referenced if possible (not a review). Hope this helps cause we really have to put all our info together soon. M. --[[User:Z3333865|Z3333865]] 12:40, 14 September 2012 (EST)
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Hey guys, for the history, im not 100% what I supposed to write about, i know its late and i'm an idiot for asking now, but am i supposed to write like the old research papers like what they used to think? like how they thought the ear formed like from the 1800's or whatever? and how technologies also helped proved it wrong or proved that they are right? P. --[[User:Z3333431|Z3333431]] 13:13, 12 September 2012 (EST)
------------
DW, I had a look at the editing basics and the references are working now! :) M. --[[User:Z3333865|Z3333865]] 10:20, 3 September 2012 (EST)

----------
Hey ppl!

I can't seem to link my references. '9' and '10' in my inner ear section step 2 should be the same number, but I can't seem to get it to work... can anyone help?

Thanks, M. --[[User:Z3333865|Z3333865]] 09:46, 3 September 2012 (EST)

--------------------

To all,
I find it very difficult to find images which have the correct copyright statement and are not already used on this embryology website.
So if anyone finds an image which we are allowed to use, please post it up and let the others know :)

And to B. That sounds good :) Speak to you tomorrow! M. --[[User:Z3333865|Z3333865]] 13:22, 27 August 2012 (EST)

----------
Hi!

In regards to my abnormalities (we can all discuss further this week), I will be focussing mainly on the gene GJB2 (which accounts for 50% of non syndromic hearing) and then for acquired hearing (organisms), I will focus mainly on what is known as "TORCH" organisms (i.e., toxoplasmosis, rubella, cytomegalic virus, and herpes) and go into details in them and then as M said before, just list the other in a table.

Thanks,
B. --[[User:Z3292017|Z3292017]] 17:45, 26 August 2012 (EST)

----------

Hey!

In regards to the hearing abnormalities, yes I would do the most common ones. It will be way too much otherwise!
Just name the other abnormalities for now - depending on how long your section is we will include them or leave out.
At the end of your section we can also put a table down with a summary of the common ones you explained in detail before :)

M. --[[User:Z3333865|Z3333865]] 13:07, 26 August 2012 (EST)

----------

Hey guys,

Sorry I haven't been communicating via the discussion page, I've been sick in bed with a virus for the past week and half! Anyway, as I am focussing on the hearing abnormalities, I just wanted to clarify some things with you all. Firstly, there are A LOT of genetic disorder which contribute to hearing loss so I was thinking I would group them and would write in depth into the most common ones and then a brief description or just name the others.
I'm currently compiling some research papers, so I will most likely get to writing some points on this page tomorrow.

Let me know if you have any suggestiosn etc and if I find any other articles in my research I will send them through!
--[[User:Z3292017|Z3292017]] 18:44, 25 August 2012 (EST)

----------

Hey all!

For this week, please find some good papers relating to your section - both primary and secondary - and start reading them.
It will take some time to get all the info together and to also make it look good with pictures etc.
So the sooner we start the easier it will be in the long-run!!

--[[User:Z3333865|Z3333865]] 21:00, 18 August 2012 (EST)

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Hey everyone!

I guess if we end up doing the sensory topic and focus on the ear we can come up with some headings that we might want to use in our project.

This is the [[Sensory_-_Hearing_and_Balance_Development| link to our lecture on the ear]]

I guess one way of doing this would be to divide it into inner, middle and outer ear and talk about the development of each. I guess we could include the progressive development over the weeks including cellular, molecular and morphological changes. We can also describe the developed ear, any genetic mutations or incorrect signal pathway that cause any defects. Then one part of it can be current research and any past research or noble prizes.

Cheers!

--[[User:Z3333794|Z3333794]] 11:31, 9 August 2012 (EST)

--------------------------------------------
Hey all!

So we have to decide between normal development or abnormal development.
Normal development can have headings as mentioned above, apart from the genetic mutations and defects.
When focussing on abnormal development of the ear we can look at those mutations and defects. We can also look at technology such as hearing aids and the cochlear implant.

Please put down your preference!
I really dont care.. but I think that if we have to discuss development it will be easiest to look at normal development.

--[[User:Z3333865|Z3333865]] 13:06, 14 August 2012 (EST)

User:Z3254758

2012-09-20T14:34:22Z

Z3254758: /* Lab 7 */

User:Z3254758

2012-09-20T14:30:40Z

Z3254758: /* Lab 7 */

2012 Group Project 1

2012-09-19T01:57:47Z

Z3254758: /* Aqueous Chambers */

2012 Group Project 1

2012-09-19T01:56:36Z

Z3254758: /* Iris */

2012 Group Project 1

2012-09-19T01:40:52Z

Z3254758: /* Introduction */

2012 Group Project 1

2012-09-19T01:32:23Z

Z3254758: /* Introduction */

2012 Group Project 1

2012-09-19T01:30:32Z

Z3254758: /* Useful links */

2012 Group Project 1

2012-09-19T01:29:27Z

Z3254758: /* Current research */

2012 Group Project 1

2012-09-19T01:28:40Z

Z3254758: /* Current research */

2012 Group Project 1

2012-09-19T00:52:04Z

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2012 Group Project 1

2012-09-19T00:51:45Z

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2012 Group Project 1

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Z3254758: /* Image gallery */

2012 Group Project 1

2012-09-19T00:44:08Z

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Z3254758: /* Lab Attendance */