Embryology - User contributions [en-gb]

User:Z3373894

2012-10-17T02:38:03Z

Z3373894:

==Lab Attendance==

Lab 1 -- [[User:Z3373894|Z3373894]] 11:49, 25 July 2012 (EST)

Lab 2 -- [[User:Z3373894|Z3373894]] 10:37, 1 August 2012 (EST)

Lab 3 -- [[User:Z3373894|Z3373894]] 10:06, 8 August 2012 (EST)

Lab 4 -- [[User:Z3373894|Z3373894]] 10:23, 15 August 2012 (EST)

Lab 5 -- [[User:Z3373894|Z3373894]] 10:05, 22 August 2012 (EST)

Lab 6 -- [[User:Z3373894|Z3373894]] 10:02, 29 August 2012 (EST)

Lab 7 -- [[User:Z3373894|Z3373894]] 10:14, 12 September 2012 (EST)

Lab 8 -- Attended lab but forgot to sign attendance. Sorry!

Lab 9 -- [[User:Z3373894|Z3373894]] 10:02, 26 September 2012 (EST)

Lab 10 -- [[User:Z3373894|Z3373894]] 10:06, 3 October 2012 (EST)

Lab 11 -- [[User:Z3373894|Z3373894]] 10:04, 10 October 2012 (EST)

Lab 12 -- [[User:Z3373894|Z3373894]] 10:08, 17 October 2012 (EST)

==Lab 1 Assessment==

'''1. Identify the origin of In Vitro Fertilization and the 2010 nobel prize winner associated with this technique and add a correctly formatted link to the Nobel page.'''

In vitro fertilisation (IVF) has its origins in the 1970s, specifically 1978 when the first successful birth of an IVF baby occurred. This birth was the result of the work of physiologist [http://www.nobelprize.org/nobel_prizes/medicine/laureates/2010/edwards.html Robert G. Edwards], who developed the technique and subsequently won the [http://www.nobelprize.org/nobel_prizes/medicine/laureates/2010/ Nobel Prize in Physiology or Medicine 2010] for his work. The procedure involves removing a healthy ovum from the mother and fertilising it outside of the female's body, where the term ''in vitro'', which is Latin for "in glass" comes from. Today, this term is used to describe any procedure that takes place outside of the body, in opposition to an ''in vivo'' procedure which takes place inside the body. The zygote is then implanted back into the woman's uterus where it can develop normally.<ref>http://en.wikipedia.org/wiki/In_vitro_fertilisation</ref>

'''2. Identify and add a PubMed reference link to a recent paper on fertilisation and describe its key findings (1-2 paragraphs).'''

A recent paper published on the topic of fertilisation includes a paper from researchers at the University of Pisa in Italy entitled ''DHEA supplementation improves follicular microenviroment in poor responder patients''.<ref><pubmed>22835219</pubmed></ref> This study looked at a group of 24 women aged between 31 and 42 diagnosed with poor ovarian response (POR) in which fewer follicles properly develop. These women were randomly split into two groups; one of which received no special treatment prior to IVF, while the other group received dehydroepiandrosterone (DHEA) supplementation, which was hypothesised to increase the quality of the oocytes and therefore increase the chance of a successful pregnancy.

The results showed that the group of women that received DHEA supplementation prior to IVF had lower levels of HIF1 in their follicular fluid; a substance produced by the body in response to low oxygen levels. This suggests that DHEA increases the supply of oxygen to the developing follicle and thus increases its quality, as it had been previously shown that oxygen plays a very important role in follicle development. Although the study demonstrated with statistical significance that supplementation with DHEA led to higher levels of HIF1, it could not be shown that supplementation led to better IVF outcomes, however this was attributed to the small sample size. The study concluded that DHEA supplementation is a viable option to increasing follicle development in women with POR as it is relatively cheap, easily administered and has minimal side effects.

==Lab 2 Assessment==

[[File:Macaque Oocyte.jpg|200px|thumb|left|A recently fertilised macaque oocyte.<ref><pubmed>20591337</pubmed></ref>]]

'''1. Upload an image from a journal source relating to fertilization or the first 2 weeks of development as demonstrated in the practical class. Including in the image “Summary” window: An image name as a section heading, Any further description of what the image shows, A subsection labeled “Reference” and under this the original image source, appropriate reference and all copyright information and finally a template indicating that this is a student image. {{Template:Student Image}}'''

The image to the left is from a journal article that investigated both in vivo and in vitro fertilisation in the macaque monkey. It shows a macaque oocyte containing both the maternal and paternal pronuclei. The link to this article can be found both below in 'references' and also in the description of the image.

'''2. Identify a protein associated with the implantation process, including a brief description of the protein's role.
'''

A protein associated with the implantation process is the glycoprotein ''fibronectin.'' It is involved in cell adhesion, growth, migration and differentiation; making it important in many bodily processes including wound healing and embryo implantation. In implantation, it guides cell attachment and migration, and the absence of fibronectin leads to defects in mesodermal, neural tube and vascular development; causing early embryo death.<ref>http://en.wikipedia.org/wiki/Fibronectin</ref>

==Lab 3 Assessment==

'''1. Identify the difference between "gestational age" and "post-fertilisation age" and explain why clinically "gestational age" is used in describing human development.'''

Gestational age is the time that has elapsed since the pregnant woman's last menstrual period began, measured in weeks. Post-fertilisation age is the time that has elapsed since the oocyte was fertilised by the sperm, also measured in weeks. Fertilisation reliably occurs 2 weeks after the last menstrual period, so gestational age is roughly 2 weeks greater than the post-fertilisation age. Gestational age is used clinically to describe human development as it is often difficult to identify the precise timing of fertilisation, thus the time since the last menstrual period (gestational age) is more convenient. Using gestational age, a pregnancy can be identified as premature or postmature. This identification has implications for a successful birth, as premature babies have a greater risk of complications and death.<ref>http://en.wikipedia.org/wiki/Gestational_age</ref>

'''2. Identify using histological descriptions at least 3 different types of tissues formed from somites.'''

Three different types of tissues formed from somites include the dermis (from dermatomes), skeletal muscle (from myotomes) and bone (from sclerotomes). Histologically, the dermis is an area of connective tissue under the outer, keratinised epidermis, that contains blood vessels and nerve endings. Skeletal muscle is muscle that appears striated and is under voluntary control by the nervous system. Bone is a specialised form of connective tissue that is organised into compact and spongy forms. The compact components provide rigidity while spongy bone works to distribute loads across the bone.<ref>http://en.wikipedia.org/wiki/Somite</ref>

==Lab 4 Assessment==

'''1. Identify the 2 invasive prenatal diagnostic techniques related to the placenta and 2 abnormalities that can be identified with these techniques.'''

An invasive prenatal diagnostic technique related to the placenta is an amniocentesis. This involves inserting a needle through the mother's abdomen and collecting a sample of the amniotic fluid, which contains cells shed by the fetus. Through analysis, this technique can identify chromosomal disorders such as Down syndrome as well as open neural tube defects such as spina bifida.<ref>http://www.knowyourgenes.org/prenatal_testing.shtml</ref>

Another invasive prenatal diagnostic technique is chorionic villus sampling (CVS). This involves inserting a catheter through the cervix and removing a small sample of placental tissue, which has the same genetic material as the fetus. This can then be tested for chromosomal abnormalities like Down syndrome, however cannot detect neural tube defects such as spina bifida, which an amniocentesis can detect.<ref>http://www.hopkinsmedicine.org/healthlibrary/conditions/a/pregnancy_and_childbirth/common_tests_during_pregnancy_85,P01241/</ref>

'''2. Identify a paper that uses cord stem cells therapeutically and write a brief (2-3 paragraph) description of the paper's findings.'''

A paper that uses umbilical cord stem cells therapeutically is one from a group of researchers at Seoul National University in South Korea entitled ''Comparison of Mesenchymal Stem Cells Derived from Fat, Bone Marrow, Wharton's Jelly, and Umbilical Cord Blood for Treating Spinal Cord Injuries in Dogs.''<ref><pubmed>22878503</pubmed></ref> They induced spinal cord injuries in dogs through the use of balloon catheter compression and then applied stem cells from a variety of sources to the site of injury and compared the recovery that was achieved between the different groups.

It was found that all stem cell treatments produced significant improvements in locomotion at 8 weeks after implantation, and that this was accompanied by increased numbers of neurons and neurofilament-positive fibers at the lesion site. However it was also found that even though the umbilical cord stem cells produced no greater improvement in locomotion than the other stem cells, the umbilical cord stem cells produced more nerve regeneration and anti-inflammation activity.

==Lab 5 Assessment==

'''Completing the in class Quiz!'''

==Lab 6 Assessment==

'''To Be added.'''

==Lab 7 Assessment==

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

A muscle satellite cell is a mononuclear progenitor cell containing very little cytoplasm found between muscle fibres.

Two examples of when satellite cells are activated occur during normal muscle growth and when the muscle is damaged. In both cases, under mechanical strain the satellite cells are activated and either form new muscle fibres or fuse to existing muscle fibres to make them larger.<ref>http://en.wikipedia.org/wiki/Myosatellite_cell</ref>

==Lab 8 Assessment==

'''Individual assessment this week relates to your group project.'''

'''1. Each student should now look at each of the other Group projects in the class.'''

'''2. Next prepare a critical assessment (should include both positive and negative issues) of each project using the project assessment criteria.'''

'''3. This assessment should be pasted without signature on the top of the specific project's discussion page (minimum length 3-5 paragraphs/project).'''

'''4. This critical assessment should also be pasted on your own student page. Each student should therefore have 5 separate reports pasted on their own page for this assessment item. Length, quality and accuracy of your reports will be part of the overall mark for this assessment (there will be a greater loading on this than simple question assessments).'''

'''Somatosensory'''

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.

----

'''Taste'''

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.

----

'''Olfaction'''

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.

----

'''Abnormal Vision'''

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.

----

'''Hearing'''

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.

==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.'''

A recent research paper on the development of the pancreas is one from 2000 (getting a bit old now, I suppose) entitled ''Regulation of pancreas development by hedgehog signaling.''<ref><pubmed>11044404</pubmed></ref> In this paper, the researchers investigated the effect that the factors Sonic hedgehog, Indian hedgehog and Patched 1 have on development of the pancreas by observing the effect that mutations leading to the absence of these factors have on the organism. They found that Sonic hedgehog represses the growth of the pancreas and is important in limiting its size. For example, if the tissues surrounding the pancreas are not expressing Sonic hedgehog, then the pancreas will grow uncontrollably up to three times its usual mass with much more pancreatic islets than usual, thus impairing the normal functioning of the tissues around it including the stomach and duodenum. They also found that Indian hedgehog plays a different role than Sonic, in that it is required for normal growth rather than repressing growth. In organisms where Sonic was absent along with Indian, there was no observed abnormally large growth, as seen when Sonic was absent but Indian was present. Finally, it was also concluded that without Patched 1, the pancreas is unable to maintain glucose homeostasis.

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

The developing teeth are composed of neural crest-derived mesenchyme and ectoderm from the first pharyngeal arch. Inductive processes occur between these two embryonic tissue types at week 6 to produce the first sign of teeth (teeth buds) in a process known as odontogenesis.<ref><pubmed>19266065</pubmed></ref>

==Lab 10 Assessment==

'''To be added after practical.'''

==Lab 11 Assessment==

'''Identify a recent research article (using the pubmed tags to cite) on iPS cells and summarise in a few paragraphs the main findings of the paper.'''

A recent research article on induced pluripotent stem (iPS) cells is one entitled ''iPS cells reprogrammed from human mesenchymal-like stem/progenitor cells of dental tissue origin'' from Columbia University, New York, in 2010.<ref><pubmed>19795982</pubmed></ref> The article acknowledged the usefulness of iPS cells in medical treatments and therapies but noted that human sources of precursor cells to be induced are limited to only a few types, notably dermal fibroblasts on which the original studies were carried out. The paper investigated a new source of human iPS cells - cells derived from dental tissue.

Such dental tissue is readily available through the deciduous teeth lost in childhood and the third molars which are commonly removed in adulthood. Using ectomesenchyme derived cells from such dental tissue, they were able to induce pluripotency in the cells using either the four factors Lin28/Nanog/Oct4/Sox2 or c-Myc/Klf4/Oct4/Sox2. The iPS cells that were produced exhibited a morphology indistinguishable from human embryonic stem cells, and the paper concluded that dental tissue serves as an excellent alternative resource for generating iPS cells.

==References==

<references/>

User:Z3373894

2012-10-17T02:18:39Z

Z3373894:

==Lab Attendance==

Lab 1 -- [[User:Z3373894|Z3373894]] 11:49, 25 July 2012 (EST)

Lab 2 -- [[User:Z3373894|Z3373894]] 10:37, 1 August 2012 (EST)

Lab 3 -- [[User:Z3373894|Z3373894]] 10:06, 8 August 2012 (EST)

Lab 4 -- [[User:Z3373894|Z3373894]] 10:23, 15 August 2012 (EST)

Lab 5 -- [[User:Z3373894|Z3373894]] 10:05, 22 August 2012 (EST)

Lab 6 -- [[User:Z3373894|Z3373894]] 10:02, 29 August 2012 (EST)

Lab 7 -- [[User:Z3373894|Z3373894]] 10:14, 12 September 2012 (EST)

Lab 8 -- Attended lab but forgot to sign attendance. Sorry!

Lab 9 -- [[User:Z3373894|Z3373894]] 10:02, 26 September 2012 (EST)

Lab 10 -- [[User:Z3373894|Z3373894]] 10:06, 3 October 2012 (EST)

Lab 11 -- [[User:Z3373894|Z3373894]] 10:04, 10 October 2012 (EST)

Lab 12 -- [[User:Z3373894|Z3373894]] 10:08, 17 October 2012 (EST)

==Lab 1 Assessment==

'''1. Identify the origin of In Vitro Fertilization and the 2010 nobel prize winner associated with this technique and add a correctly formatted link to the Nobel page.'''

In vitro fertilisation (IVF) has its origins in the 1970s, specifically 1978 when the first successful birth of an IVF baby occurred. This birth was the result of the work of physiologist [http://www.nobelprize.org/nobel_prizes/medicine/laureates/2010/edwards.html Robert G. Edwards], who developed the technique and subsequently won the [http://www.nobelprize.org/nobel_prizes/medicine/laureates/2010/ Nobel Prize in Physiology or Medicine 2010] for his work. The procedure involves removing a healthy ovum from the mother and fertilising it outside of the female's body, where the term ''in vitro'', which is Latin for "in glass" comes from. Today, this term is used to describe any procedure that takes place outside of the body, in opposition to an ''in vivo'' procedure which takes place inside the body. The zygote is then implanted back into the woman's uterus where it can develop normally.<ref>http://en.wikipedia.org/wiki/In_vitro_fertilisation</ref>

'''2. Identify and add a PubMed reference link to a recent paper on fertilisation and describe its key findings (1-2 paragraphs).'''

A recent paper published on the topic of fertilisation includes a paper from researchers at the University of Pisa in Italy entitled ''DHEA supplementation improves follicular microenviroment in poor responder patients''.<ref><pubmed>22835219</pubmed></ref> This study looked at a group of 24 women aged between 31 and 42 diagnosed with poor ovarian response (POR) in which fewer follicles properly develop. These women were randomly split into two groups; one of which received no special treatment prior to IVF, while the other group received dehydroepiandrosterone (DHEA) supplementation, which was hypothesised to increase the quality of the oocytes and therefore increase the chance of a successful pregnancy.

The results showed that the group of women that received DHEA supplementation prior to IVF had lower levels of HIF1 in their follicular fluid; a substance produced by the body in response to low oxygen levels. This suggests that DHEA increases the supply of oxygen to the developing follicle and thus increases its quality, as it had been previously shown that oxygen plays a very important role in follicle development. Although the study demonstrated with statistical significance that supplementation with DHEA led to higher levels of HIF1, it could not be shown that supplementation led to better IVF outcomes, however this was attributed to the small sample size. The study concluded that DHEA supplementation is a viable option to increasing follicle development in women with POR as it is relatively cheap, easily administered and has minimal side effects.

==Lab 2 Assessment==

[[File:Macaque Oocyte.jpg|200px|thumb|left|A recently fertilised macaque oocyte.<ref><pubmed>20591337</pubmed></ref>]]

'''1. Upload an image from a journal source relating to fertilization or the first 2 weeks of development as demonstrated in the practical class. Including in the image “Summary” window: An image name as a section heading, Any further description of what the image shows, A subsection labeled “Reference” and under this the original image source, appropriate reference and all copyright information and finally a template indicating that this is a student image. {{Template:Student Image}}'''

The image to the left is from a journal article that investigated both in vivo and in vitro fertilisation in the macaque monkey. It shows a macaque oocyte containing both the maternal and paternal pronuclei. The link to this article can be found both below in 'references' and also in the description of the image.

'''2. Identify a protein associated with the implantation process, including a brief description of the protein's role.
'''

A protein associated with the implantation process is the glycoprotein ''fibronectin.'' It is involved in cell adhesion, growth, migration and differentiation; making it important in many bodily processes including wound healing and embryo implantation. In implantation, it guides cell attachment and migration, and the absence of fibronectin leads to defects in mesodermal, neural tube and vascular development; causing early embryo death.<ref>http://en.wikipedia.org/wiki/Fibronectin</ref>

==Lab 3 Assessment==

'''1. Identify the difference between "gestational age" and "post-fertilisation age" and explain why clinically "gestational age" is used in describing human development.'''

Gestational age is the time that has elapsed since the pregnant woman's last menstrual period began, measured in weeks. Post-fertilisation age is the time that has elapsed since the oocyte was fertilised by the sperm, also measured in weeks. Fertilisation reliably occurs 2 weeks after the last menstrual period, so gestational age is roughly 2 weeks greater than the post-fertilisation age. Gestational age is used clinically to describe human development as it is often difficult to identify the precise timing of fertilisation, thus the time since the last menstrual period (gestational age) is more convenient. Using gestational age, a pregnancy can be identified as premature or postmature. This identification has implications for a successful birth, as premature babies have a greater risk of complications and death.<ref>http://en.wikipedia.org/wiki/Gestational_age</ref>

'''2. Identify using histological descriptions at least 3 different types of tissues formed from somites.'''

Three different types of tissues formed from somites include the dermis (from dermatomes), skeletal muscle (from myotomes) and bone (from sclerotomes). Histologically, the dermis is an area of connective tissue under the outer, keratinised epidermis, that contains blood vessels and nerve endings. Skeletal muscle is muscle that appears striated and is under voluntary control by the nervous system. Bone is a specialised form of connective tissue that is organised into compact and spongy forms. The compact components provide rigidity while spongy bone works to distribute loads across the bone.<ref>http://en.wikipedia.org/wiki/Somite</ref>

==Lab 4 Assessment==

'''1. Identify the 2 invasive prenatal diagnostic techniques related to the placenta and 2 abnormalities that can be identified with these techniques.'''

An invasive prenatal diagnostic technique related to the placenta is an amniocentesis. This involves inserting a needle through the mother's abdomen and collecting a sample of the amniotic fluid, which contains cells shed by the fetus. Through analysis, this technique can identify chromosomal disorders such as Down syndrome as well as open neural tube defects such as spina bifida.<ref>http://www.knowyourgenes.org/prenatal_testing.shtml</ref>

Another invasive prenatal diagnostic technique is chorionic villus sampling (CVS). This involves inserting a catheter through the cervix and removing a small sample of placental tissue, which has the same genetic material as the fetus. This can then be tested for chromosomal abnormalities like Down syndrome, however cannot detect neural tube defects such as spina bifida, which an amniocentesis can detect.<ref>http://www.hopkinsmedicine.org/healthlibrary/conditions/a/pregnancy_and_childbirth/common_tests_during_pregnancy_85,P01241/</ref>

'''2. Identify a paper that uses cord stem cells therapeutically and write a brief (2-3 paragraph) description of the paper's findings.'''

A paper that uses umbilical cord stem cells therapeutically is one from a group of researchers at Seoul National University in South Korea entitled ''Comparison of Mesenchymal Stem Cells Derived from Fat, Bone Marrow, Wharton's Jelly, and Umbilical Cord Blood for Treating Spinal Cord Injuries in Dogs.''<ref><pubmed>22878503</pubmed></ref> They induced spinal cord injuries in dogs through the use of balloon catheter compression and then applied stem cells from a variety of sources to the site of injury and compared the recovery that was achieved between the different groups.

It was found that all stem cell treatments produced significant improvements in locomotion at 8 weeks after implantation, and that this was accompanied by increased numbers of neurons and neurofilament-positive fibers at the lesion site. However it was also found that even though the umbilical cord stem cells produced no greater improvement in locomotion than the other stem cells, the umbilical cord stem cells produced more nerve regeneration and anti-inflammation activity.

==Lab 5 Assessment==

'''Completing the in class Quiz!'''

==Lab 6 Assessment==

'''To Be added.'''

==Lab 7 Assessment==

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

A muscle satellite cell is a mononuclear progenitor cell containing very little cytoplasm found between muscle fibres.

Two examples of when satellite cells are activated occur during normal muscle growth and when the muscle is damaged. In both cases, under mechanical strain the satellite cells are activated and either form new muscle fibres or fuse to existing muscle fibres to make them larger.<ref>http://en.wikipedia.org/wiki/Myosatellite_cell</ref>

==Lab 8 Assessment==

'''Individual assessment this week relates to your group project.'''

'''1. Each student should now look at each of the other Group projects in the class.'''

'''2. Next prepare a critical assessment (should include both positive and negative issues) of each project using the project assessment criteria.'''

'''3. This assessment should be pasted without signature on the top of the specific project's discussion page (minimum length 3-5 paragraphs/project).'''

'''4. This critical assessment should also be pasted on your own student page. Each student should therefore have 5 separate reports pasted on their own page for this assessment item. Length, quality and accuracy of your reports will be part of the overall mark for this assessment (there will be a greater loading on this than simple question assessments).'''

'''Somatosensory'''

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.

----

'''Taste'''

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.

----

'''Olfaction'''

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.

----

'''Abnormal Vision'''

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.

----

'''Hearing'''

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.

==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.'''

A recent research paper on the development of the pancreas is one from 2000 (getting a bit old now, I suppose) entitled ''Regulation of pancreas development by hedgehog signaling.''<ref><pubmed>11044404</pubmed></ref> In this paper, the researchers investigated the effect that the factors Sonic hedgehog, Indian hedgehog and Patched 1 have on development of the pancreas by observing the effect that mutations leading to the absence of these factors have on the organism. They found that Sonic hedgehog represses the growth of the pancreas and is important in limiting its size. For example, if the tissues surrounding the pancreas are not expressing Sonic hedgehog, then the pancreas will grow uncontrollably up to three times its usual mass with much more pancreatic islets than usual, thus impairing the normal functioning of the tissues around it including the stomach and duodenum. They also found that Indian hedgehog plays a different role than Sonic, in that it is required for normal growth rather than repressing growth. In organisms where Sonic was absent along with Indian, there was no observed abnormally large growth, as seen when Sonic was absent but Indian was present. Finally, it was also concluded that without Patched 1, the pancreas is unable to maintain glucose homeostasis.

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

The developing teeth are composed of neural crest-derived mesenchyme and ectoderm from the first pharyngeal arch. Inductive processes occur between these two embryonic tissue types at week 6 to produce the first sign of teeth (teeth buds) in a process known as odontogenesis.<ref><pubmed>19266065</pubmed></ref>

==Lab 10 Assessment==

'''To be added after practical.'''

==Lab 11 Assessment==

'''Identify a recent research article (using the pubmed tags to cite) on iPS cells and summarise in a few paragraphs the main findings of the paper.'''

A recent research article on iPS cells is one entitled ''iPS cells reprogrammed from human mesenchymal-like stem/progenitor cells of dental tissue origin'' from Columbia University, New York, in 2010.<ref><pubmed>19795982</pubmed></ref>

==References==

<references/>

User:Z3373894

2012-10-16T23:08:18Z

Z3373894:

User:Z3373894

2012-10-09T23:04:04Z

Z3373894:

==Lab Attendance==

Lab 1 -- [[User:Z3373894|Z3373894]] 11:49, 25 July 2012 (EST)

Lab 2 -- [[User:Z3373894|Z3373894]] 10:37, 1 August 2012 (EST)

Lab 3 -- [[User:Z3373894|Z3373894]] 10:06, 8 August 2012 (EST)

Lab 4 -- [[User:Z3373894|Z3373894]] 10:23, 15 August 2012 (EST)

Lab 5 -- [[User:Z3373894|Z3373894]] 10:05, 22 August 2012 (EST)

Lab 6 -- [[User:Z3373894|Z3373894]] 10:02, 29 August 2012 (EST)

Lab 7 -- [[User:Z3373894|Z3373894]] 10:14, 12 September 2012 (EST)

Lab 8 -- Attended lab but forgot to sign attendance. Sorry!

Lab 9 -- [[User:Z3373894|Z3373894]] 10:02, 26 September 2012 (EST)

Lab 10 -- [[User:Z3373894|Z3373894]] 10:06, 3 October 2012 (EST)

Lab 11 -- [[User:Z3373894|Z3373894]] 10:04, 10 October 2012 (EST)

==Lab 1 Assessment==

'''1. Identify the origin of In Vitro Fertilization and the 2010 nobel prize winner associated with this technique and add a correctly formatted link to the Nobel page.'''

In vitro fertilisation (IVF) has its origins in the 1970s, specifically 1978 when the first successful birth of an IVF baby occurred. This birth was the result of the work of physiologist [http://www.nobelprize.org/nobel_prizes/medicine/laureates/2010/edwards.html Robert G. Edwards], who developed the technique and subsequently won the [http://www.nobelprize.org/nobel_prizes/medicine/laureates/2010/ Nobel Prize in Physiology or Medicine 2010] for his work. The procedure involves removing a healthy ovum from the mother and fertilising it outside of the female's body, where the term ''in vitro'', which is Latin for "in glass" comes from. Today, this term is used to describe any procedure that takes place outside of the body, in opposition to an ''in vivo'' procedure which takes place inside the body. The zygote is then implanted back into the woman's uterus where it can develop normally.<ref>http://en.wikipedia.org/wiki/In_vitro_fertilisation</ref>

'''2. Identify and add a PubMed reference link to a recent paper on fertilisation and describe its key findings (1-2 paragraphs).'''

A recent paper published on the topic of fertilisation includes a paper from researchers at the University of Pisa in Italy entitled ''DHEA supplementation improves follicular microenviroment in poor responder patients''.<ref><pubmed>22835219</pubmed></ref> This study looked at a group of 24 women aged between 31 and 42 diagnosed with poor ovarian response (POR) in which fewer follicles properly develop. These women were randomly split into two groups; one of which received no special treatment prior to IVF, while the other group received dehydroepiandrosterone (DHEA) supplementation, which was hypothesised to increase the quality of the oocytes and therefore increase the chance of a successful pregnancy.

The results showed that the group of women that received DHEA supplementation prior to IVF had lower levels of HIF1 in their follicular fluid; a substance produced by the body in response to low oxygen levels. This suggests that DHEA increases the supply of oxygen to the developing follicle and thus increases its quality, as it had been previously shown that oxygen plays a very important role in follicle development. Although the study demonstrated with statistical significance that supplementation with DHEA led to higher levels of HIF1, it could not be shown that supplementation led to better IVF outcomes, however this was attributed to the small sample size. The study concluded that DHEA supplementation is a viable option to increasing follicle development in women with POR as it is relatively cheap, easily administered and has minimal side effects.

==Lab 2 Assessment==

[[File:Macaque Oocyte.jpg|200px|thumb|left|A recently fertilised macaque oocyte.<ref><pubmed>20591337</pubmed></ref>]]

'''1. Upload an image from a journal source relating to fertilization or the first 2 weeks of development as demonstrated in the practical class. Including in the image “Summary” window: An image name as a section heading, Any further description of what the image shows, A subsection labeled “Reference” and under this the original image source, appropriate reference and all copyright information and finally a template indicating that this is a student image. {{Template:Student Image}}'''

The image to the left is from a journal article that investigated both in vivo and in vitro fertilisation in the macaque monkey. It shows a macaque oocyte containing both the maternal and paternal pronuclei. The link to this article can be found both below in 'references' and also in the description of the image.

'''2. Identify a protein associated with the implantation process, including a brief description of the protein's role.
'''

A protein associated with the implantation process is the glycoprotein ''fibronectin.'' It is involved in cell adhesion, growth, migration and differentiation; making it important in many bodily processes including wound healing and embryo implantation. In implantation, it guides cell attachment and migration, and the absence of fibronectin leads to defects in mesodermal, neural tube and vascular development; causing early embryo death.<ref>http://en.wikipedia.org/wiki/Fibronectin</ref>

==Lab 3 Assessment==

'''1. Identify the difference between "gestational age" and "post-fertilisation age" and explain why clinically "gestational age" is used in describing human development.'''

Gestational age is the time that has elapsed since the pregnant woman's last menstrual period began, measured in weeks. Post-fertilisation age is the time that has elapsed since the oocyte was fertilised by the sperm, also measured in weeks. Fertilisation reliably occurs 2 weeks after the last menstrual period, so gestational age is roughly 2 weeks greater than the post-fertilisation age. Gestational age is used clinically to describe human development as it is often difficult to identify the precise timing of fertilisation, thus the time since the last menstrual period (gestational age) is more convenient. Using gestational age, a pregnancy can be identified as premature or postmature. This identification has implications for a successful birth, as premature babies have a greater risk of complications and death.<ref>http://en.wikipedia.org/wiki/Gestational_age</ref>

'''2. Identify using histological descriptions at least 3 different types of tissues formed from somites.'''

Three different types of tissues formed from somites include the dermis (from dermatomes), skeletal muscle (from myotomes) and bone (from sclerotomes). Histologically, the dermis is an area of connective tissue under the outer, keratinised epidermis, that contains blood vessels and nerve endings. Skeletal muscle is muscle that appears striated and is under voluntary control by the nervous system. Bone is a specialised form of connective tissue that is organised into compact and spongy forms. The compact components provide rigidity while spongy bone works to distribute loads across the bone.<ref>http://en.wikipedia.org/wiki/Somite</ref>

==Lab 4 Assessment==

'''1. Identify the 2 invasive prenatal diagnostic techniques related to the placenta and 2 abnormalities that can be identified with these techniques.'''

An invasive prenatal diagnostic technique related to the placenta is an amniocentesis. This involves inserting a needle through the mother's abdomen and collecting a sample of the amniotic fluid, which contains cells shed by the fetus. Through analysis, this technique can identify chromosomal disorders such as Down syndrome as well as open neural tube defects such as spina bifida.<ref>http://www.knowyourgenes.org/prenatal_testing.shtml</ref>

Another invasive prenatal diagnostic technique is chorionic villus sampling (CVS). This involves inserting a catheter through the cervix and removing a small sample of placental tissue, which has the same genetic material as the fetus. This can then be tested for chromosomal abnormalities like Down syndrome, however cannot detect neural tube defects such as spina bifida, which an amniocentesis can detect.<ref>http://www.hopkinsmedicine.org/healthlibrary/conditions/a/pregnancy_and_childbirth/common_tests_during_pregnancy_85,P01241/</ref>

'''2. Identify a paper that uses cord stem cells therapeutically and write a brief (2-3 paragraph) description of the paper's findings.'''

A paper that uses umbilical cord stem cells therapeutically is one from a group of researchers at Seoul National University in South Korea entitled ''Comparison of Mesenchymal Stem Cells Derived from Fat, Bone Marrow, Wharton's Jelly, and Umbilical Cord Blood for Treating Spinal Cord Injuries in Dogs.''<ref><pubmed>22878503</pubmed></ref> They induced spinal cord injuries in dogs through the use of balloon catheter compression and then applied stem cells from a variety of sources to the site of injury and compared the recovery that was achieved between the different groups.

It was found that all stem cell treatments produced significant improvements in locomotion at 8 weeks after implantation, and that this was accompanied by increased numbers of neurons and neurofilament-positive fibers at the lesion site. However it was also found that even though the umbilical cord stem cells produced no greater improvement in locomotion than the other stem cells, the umbilical cord stem cells produced more nerve regeneration and anti-inflammation activity.

==Lab 5 Assessment==

'''Completing the in class Quiz!'''

==Lab 6 Assessment==

'''To Be added.'''

==Lab 7 Assessment==

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

A muscle satellite cell is a mononuclear progenitor cell containing very little cytoplasm found between muscle fibres.

Two examples of when satellite cells are activated occur during normal muscle growth and when the muscle is damaged. In both cases, under mechanical strain the satellite cells are activated and either form new muscle fibres or fuse to existing muscle fibres to make them larger.<ref>http://en.wikipedia.org/wiki/Myosatellite_cell</ref>

==Lab 8 Assessment==

'''Individual assessment this week relates to your group project.'''

'''1. Each student should now look at each of the other Group projects in the class.'''

'''2. Next prepare a critical assessment (should include both positive and negative issues) of each project using the project assessment criteria.'''

'''3. This assessment should be pasted without signature on the top of the specific project's discussion page (minimum length 3-5 paragraphs/project).'''

'''4. This critical assessment should also be pasted on your own student page. Each student should therefore have 5 separate reports pasted on their own page for this assessment item. Length, quality and accuracy of your reports will be part of the overall mark for this assessment (there will be a greater loading on this than simple question assessments).'''

'''Somatosensory'''

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.

----

'''Taste'''

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.

----

'''Olfaction'''

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.

----

'''Abnormal Vision'''

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.

----

'''Hearing'''

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.

==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.'''

A recent research paper on the development of the pancreas is one from 2000 (getting a bit old now, I suppose) entitled ''Regulation of pancreas development by hedgehog signaling.''<ref><pubmed>11044404</pubmed></ref> In this paper, the researchers investigated the effect that the factors Sonic hedgehog, Indian hedgehog and Patched 1 have on development of the pancreas by observing the effect that mutations leading to the absence of these factors have on the organism. They found that Sonic hedgehog represses the growth of the pancreas and is important in limiting its size. For example, if the tissues surrounding the pancreas are not expressing Sonic hedgehog, then the pancreas will grow uncontrollably up to three times its usual mass with much more pancreatic islets than usual, thus impairing the normal functioning of the tissues around it including the stomach and duodenum. They also found that Indian hedgehog plays a different role than Sonic, in that it is required for normal growth rather than repressing growth. In organisms where Sonic was absent along with Indian, there was no observed abnormally large growth, as seen when Sonic was absent but Indian was present. Finally, it was also concluded that without Patched 1, the pancreas is unable to maintain glucose homeostasis.

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

The developing teeth are composed of neural crest-derived mesenchyme and ectoderm from the first pharyngeal arch. Inductive processes occur between these two embryonic tissue types at week 6 to produce the first sign of teeth (teeth buds) in a process known as odontogenesis.<ref><pubmed>19266065</pubmed></ref>

==Lab 10 Assessment==

'''To be added after practical.'''

==References==

<references/>

2012 Group Project 1

2012-10-05T03:25:33Z

Z3373894:

[[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

*Vitreous

*Extraocular muscles

|[[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. Credits: Webvision <ref name="Kolb H, Fernandez E, Nelson R. '''The Organization of the Retina and Visual System ''' (Online Book). PMID:[http://www.ncbi.nlm.nih.gov/pubmed/21413389 21413389] [PubMed]
">Kolb H, Fernandez E, Nelson R. '''The Organization of the Retina and Visual System ''' (Online Book). PMID:[http://www.ncbi.nlm.nih.gov/pubmed/21413389 21413389] [PubMed]
</ref>
]]
|}
[[File:Eyediagramcolour1.JPG|550px]]

The '''cornea''' is 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. It consists of 5 layers: anterior epithelium, bowman's layer, stroma, descemet's layer, and endothelium. <ref name="Remington L.A. (2012) Clinical Anatomy of the Visual System. 3rd Ed. Elsevier 2012.">Remington L.A. (2012) Clinical Anatomy of the Visual System. 3rd Ed. Elsevier 2012.</ref>

The '''pupil''' is an opening in the anterior part of the eye, which controls how much light enters the eye. <ref name="Remington L.A. (2012) Clinical Anatomy of the Visual System. 3rd Ed. Elsevier 2012."/>

The '''iris''' is A circular shaped muscle which controls the opening and contraction of the pupil. <ref name="Remington L.A. (2012) Clinical Anatomy of the Visual System. 3rd Ed. Elsevier 2012."/>

The '''sclera''' is the white external anterior surface of the eye, which envelopes the eyeball to give it support and protection of its internal contents. <ref name="Remington L.A. (2012) Clinical Anatomy of the Visual System. 3rd Ed. Elsevier 2012."/>

The '''lens''' is a structure inside the eye which refracts light as it enters the eye for clear vision. <ref name="Remington L.A. (2012) Clinical Anatomy of the Visual System. 3rd Ed. Elsevier 2012."/>

'''Optic Nerve''' is the nerve which carries visual information from the retina to the brain for processing. <ref name="Remington L.A. (2012) Clinical Anatomy of the Visual System. 3rd Ed. Elsevier 2012."/>

The '''choroid''' is the middle coat of the eye, located between the sclera and retina, which contains blood vessels that nourish the structures in the eye. <ref name="Remington L.A. (2012) Clinical Anatomy of the Visual System. 3rd Ed. Elsevier 2012."/>

The '''ciliary body''' is a 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. <ref name="Remington L.A. (2012) Clinical Anatomy of the Visual System. 3rd Ed. Elsevier 2012."/>

'''Extraocular muscles''' are the six muscles that control the movement of the eyeball. They are lateral rectus, medial rectus, superior rectus, inferior rectus, superior oblique, inferior oblique. <ref name="Remington L.A. (2012) Clinical Anatomy of the Visual System. 3rd Ed. Elsevier 2012."/>

[[File:Extraocular-muscles-scan.jpg|thumb|200px|A CAT scan with illustrations to show the '''extraocular muscles''' from the back view of the eye.
Credits: Webvision <ref name="Kolb H, Fernandez E, Nelson R. '''The Organization of the Retina and Visual System ''' (Online Book). PMID:[http://www.ncbi.nlm.nih.gov/pubmed/21413389 21413389] [PubMed]
"/>
]]

'''Anterior chamber''' is the fluid-filled area located between the iris and cornea. <ref name="Remington L.A. (2012) Clinical Anatomy of the Visual System. 3rd Ed. Elsevier 2012."/>

'''Posterior chamber''' is the fluid-filled area located between the iris and lens. <ref name="Remington L.A. (2012) Clinical Anatomy of the Visual System. 3rd Ed. Elsevier 2012."/>

'''Vitreous Chamber''' is the area located between the lens and retina, which contains vitreous (a gel like substance) whose function is to maintain the shape of the eye. <ref name="Remington L.A. (2012) Clinical Anatomy of the Visual System. 3rd Ed. Elsevier 2012."/>

The '''retina''' is a light-sensitive layer 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. The retina is made up of approximately 10 layers as follows: retinal pigment epithelium, photoreceptor cell layer, external limiting membrane, outer nuclear layer, outer plexiform layer, inner nuclear layer, inner plexiform layer, ganglion cell layer, nerve fiber layer, and internal limiting membrane. <ref name="Remington L.A. (2012) Clinical Anatomy of the Visual System. 3rd Ed. Elsevier 2012."/>

'''Macula''' is a pigmented oval region in the central area of the retina, important for maintaining visual acuity. '''Fovea''' is the central point in the macula, which is concentrated with cones for sharp colour vision. <ref name="Remington L.A. (2012) Clinical Anatomy of the Visual System. 3rd Ed. Elsevier 2012."/>

==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>.

===Vitreous===

The primary vitreous originates from the ectoderm and mesenchyme. <ref name="Remington L.A. (2012) Clinical Anatomy of the Visual System. 3rd Ed. Elsevier 2012."/> Vitreous starts to build up within the primary vitreous space during the time the lens develops. <ref name="PMID805092"><pubmed>805092</pubmed></ref> The developing lens produces ‘fibrils’ which contribute to the components of the primary vitreous. <ref name="PMID5542135"><pubmed>5542135</pubmed></ref> Hyalocytes from the primary vitreous produces the secondary vitreous. <ref name="PMID1628748"/> <ref name="Remington L.A. (2012) Clinical Anatomy of the Visual System. 3rd Ed. Elsevier 2012."/> The neural retina also produces the secondary vitreous. <ref name="PMID1628748"/> <ref name="Remington L.A. (2012) Clinical Anatomy of the Visual System. 3rd Ed. Elsevier 2012."/> The secondary vitreous thickens at three months. <ref name="PMID1628748"/>

===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.

===Extraocular Muscles===

The extraocular muscles originates from the mesenchyme. <ref name="Remington L.A. (2012) Clinical Anatomy of the Visual System. 3rd Ed. Elsevier 2012."/> The neural crest gives rise to the connective tissue of the extraocular muscles, while the mesoderm gives rise to the muscle cells. <ref name="PMID1628748"/> <ref name="PMID16249499"><pubmed>16249499</pubmed></ref> The first pair of somites gives rise to the medial rectus, superior rectus, inferior rectus, and inferior oblique muscles at day 26. <ref name="Remington L.A. (2012) Clinical Anatomy of the Visual System. 3rd Ed. Elsevier 2012."/> At day 27, the mesenchyme gives rise to the lateral rectus muscle. <ref name="Remington L.A. (2012) Clinical Anatomy of the Visual System. 3rd Ed. Elsevier 2012."/> On day 29, the second pair of somites gives rise to the superior oblique muscle. <ref name="PMID1628748"/> It takes 18 months for the tendinous sheath which attaches the extraocular muscles to the sclera to completely take formation. <ref name="PMID1628748"/>

==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>.

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

[[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.

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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."''']]
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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 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''']]
|}

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===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.

'''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

2012-10-03T00:27:58Z

Z3373894:

[[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>

{| 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]- 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
|-
| 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.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.

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{{2012Projects}}

2012 Group Project 1

2012-10-03T00:26:59Z

Z3373894: /* Eyelids */

[[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>

{| 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
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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>

{| 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]

[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/>

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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}}

File:Formation of the eyelid 2.jpg

2012-10-03T00:25:14Z

Z3373894:

A schematic showing the eye after week 8 of development. Note that all major components are now in place, however the eyelids remain fused until weeks 26-28.

Copyright: This is a student drawn image and is free for non-profit reuse.

--[[User:Z8600021|Mark Hill]] 00:37, 3 October 2012 (EST) There is no timing information provided here. This simple diagram requires more information to be useful in your project.

{{Template:Student Image}}

File:Kollmann699.jpg

2012-10-03T00:17:07Z

Z3373894:

{{Kollmann1907}}

[[Category:Vision]]

Fig. 699. Der embryonale Bulbus eines menschlichen Embryo von 10,2 mm

Länge«

(Kombiniertes Bild.)
(Anatomische Sammlung in Basel.)

Die Linse hat sich jetzt von dem Ektoderm abgeschnürt, liegt aber noch
sehr oberflächlich. Zwischen ihr und der lateralen Lamelle des Augenbechers
existiert ein ansehnlicher Raum. Der Augen blasenstiel ist länger geworden
und ist samt Augenbecher und Linse von Mesoderm umschlossen, aus dem sich
die Cornea, Sclera und Chorioidea allmählich gestalten.

{{Template:Student Image}}

File:Kollmann698.jpg

2012-10-03T00:16:34Z

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{{Kollmann1907}}

[[Category:Vision]]

FiS. 698. Der embryonale Bulbus zweier menschlichen Embryonen auf ver-
schiedenen Entwicklungsstufen des Augenbechers.

Beide Bulbi aus der 4. Woche, im Durchschnitt dargestellt. Die innere
Organisation zeigt folgende Einzelheiten: i. Die Vesicula optica secundaria mit
doppelter Wandung einer äufeeren (lateralen) und einer inneren (medialen)
Lamelle. 2. Bei A das noch offene Linsengrübchen, nach Koelliker. Die
hintere Wand des LinsengrObchens ist ebenfalls bemerkbar. 3. Die Umhüllung
durch Mesoderm. Bei B (nach van Bambecke) sind die Ränder des Linsen-
grübchens bereits verwachsen und es ist ein Linsenbläschen entstanden, das
aber noch mit dem übrigen Ektoderm zusammenhängt.

{{Template:Student Image}}

File:Kollmann697.jpg

2012-10-03T00:15:58Z

Z3373894:

{{Kollmann1907}}

[[Category:Vision]]

Fig. 697. Umwandluns der primären Augenblase des menschlichen Embryo

in eine sekundäre Augenblase.

(Nach His.)

Die Linse hängt noch mit dem Ektoderm zusammen, die primäre Augen-
blase ist gegenüber der Linsenanlage eingebuchtet. In diese Einbuchtung rückt
die Linsenanlage hinein. Zwischen der Linse und der lateralen Lamelle der
Augenblase ist ein schmaler Raum, der sich später vergrößert und dem Glas-
körper seine Entwicklung gestattet. Rechts ist das Linsensäckchen nur am
Rande getroffen, links durch die Mitte.

{{Template:Student Image}}

File:Kollmann695.jpg

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{{Kollmann1907}}

[[Category:Vision]]

Fig. 695. Die Linsenanlage bei einem lOtägisen Kaninchenembryo.

(Nach Rabl.)

Die stark vorgewölbte laterale Wand der primären Augenblase ist von
einer ziemlich gut abgegrenzten Linsenplatte bedeckt, eine direkte Fortsetzung
des Ektoderms. Die Linsenplatte ist ventralwärts etwas vertieft und besteht
a|is hohen schmalen Zylinderzellen. Zwischen Augenblase und der Linsengrube
liegen einige plattgedrückte spindelförmige Zellen. In dem anstoßenden Meso-
derm befinden sich Querschnitte von Kapillaren. In dem ganzen Umfang von
der lateralen Fläche betrachtet, besitzt die Linsenplatte eine Vertiefung. Man
spricht deshalb schon von einem Linsengrübchen (Foveola lentis).

{{Template:Student Image}}

File:Kollmann694.jpg

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{{Kollmann1907}}

[[Category:Vision]]

Fig. 694. Primäre Augeoblase bei einem menschlichen Embryo von 4 mm Länge.

Frontalschnitt.
(Anatomische Sammlung in Basel.)

Die primäre Augenblase hängt durch den Augenblasenstiel mit dem
Zwischenhirn zusammen. Die ganze Anlage ist jetzt näher gegen die Grund-
platte herabgerückt. Die laterale Oberfläche der primären Augenblase ist leicht
eingesenkt, das erste Anzeichen der Entstehung der sekundären Augenblase.

{{Template:Student Image}}

File:Kollmann693.jpg

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{{Kollmann1907}}

[[Category:Vision]]

Fig. 693. Primäre Augenblase eines menschlichen Embryo von 3,2 mm Länge.

Rekonstruktion.
(Nach His.)

Vollbild von der rechten Seite gesehen. Das Hirnrohr ist nach Entfer-
nung des Ektoderms und aller ventral liegenden Organe, wie Herz, Darmrohr
usw. von links dargestellt. Die primäre Augenblase, Vesicula optica primitiva,
bildet einen etwas abgeplatteten hohlen Vorsprung am Prosencephalon, der
jetzt noch seitlich abgeht an der Berührungsgrenze von Grund- und Fltige\p\atte.

{{Template:Student Image}}

File:Kollmann692.jpg

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{{Kollmann1907}}

[[Category:Vision]]

Fig. 692. Entstehung des lichtempfindenden Apparates.

Die Augengegend als eine schalenförmige Ausbuchtung des Vorderhims noch an

der Seitenwand befindlich (Augenfeld).

(Nach Heape, aus Nussbaum S. 6.)

Später wachsen diese Augenfelder zu seitlichen Divertikeln aus und stellen
dann die primitive Augenblase dar, welche durch einen engen Kanal mit dem
Prosencephalon und später mit dem Diencephalon zusammenhängt (Vergl. die
Figg. 693 und 694.)

{{Template:Student Image}}

File:Kollmann691.jpg

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{{Kollmann1907}}

[[Category:Vision]]

Fig. 691. Erste Entstehong des lichtempfiiidenden Apparates

aus dem Kopfteil des noch weit offenen zentralen Nervensystems in Form einer
Vertiefung zu beiden Seiten des Prosencephalon (der Vorderhimanlage) (Augenfeld)

beim Maulwurf.
(Nach Heape.)

{{Template:Student Image}}

File:Eye collage 2.jpg

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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.

{{Template:Student Image}}

File:Eyediagramcolour1.JPG

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Z3373894:

Labeled diagram of a normal eye

This image is 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.

{{Template:Student Image}}

File:Eye diagram bandw.jpg

2012-10-03T00:09:18Z

Z3373894:

This image is 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.

{{Template:Student Image}}

User:Z3373894

2012-10-03T00:06:15Z

Z3373894:

==Lab Attendance==

Lab 1 -- [[User:Z3373894|Z3373894]] 11:49, 25 July 2012 (EST)

Lab 2 -- [[User:Z3373894|Z3373894]] 10:37, 1 August 2012 (EST)

Lab 3 -- [[User:Z3373894|Z3373894]] 10:06, 8 August 2012 (EST)

Lab 4 -- [[User:Z3373894|Z3373894]] 10:23, 15 August 2012 (EST)

Lab 5 -- [[User:Z3373894|Z3373894]] 10:05, 22 August 2012 (EST)

Lab 6 -- [[User:Z3373894|Z3373894]] 10:02, 29 August 2012 (EST)

Lab 7 -- [[User:Z3373894|Z3373894]] 10:14, 12 September 2012 (EST)

Lab 8 -- Attended lab but forgot to sign attendance. Sorry!

Lab 9 -- [[User:Z3373894|Z3373894]] 10:02, 26 September 2012 (EST)

Lab 10 -- [[User:Z3373894|Z3373894]] 10:06, 3 October 2012 (EST)

==Lab 1 Assessment==

'''1. Identify the origin of In Vitro Fertilization and the 2010 nobel prize winner associated with this technique and add a correctly formatted link to the Nobel page.'''

In vitro fertilisation (IVF) has its origins in the 1970s, specifically 1978 when the first successful birth of an IVF baby occurred. This birth was the result of the work of physiologist [http://www.nobelprize.org/nobel_prizes/medicine/laureates/2010/edwards.html Robert G. Edwards], who developed the technique and subsequently won the [http://www.nobelprize.org/nobel_prizes/medicine/laureates/2010/ Nobel Prize in Physiology or Medicine 2010] for his work. The procedure involves removing a healthy ovum from the mother and fertilising it outside of the female's body, where the term ''in vitro'', which is Latin for "in glass" comes from. Today, this term is used to describe any procedure that takes place outside of the body, in opposition to an ''in vivo'' procedure which takes place inside the body. The zygote is then implanted back into the woman's uterus where it can develop normally.<ref>http://en.wikipedia.org/wiki/In_vitro_fertilisation</ref>

'''2. Identify and add a PubMed reference link to a recent paper on fertilisation and describe its key findings (1-2 paragraphs).'''

A recent paper published on the topic of fertilisation includes a paper from researchers at the University of Pisa in Italy entitled ''DHEA supplementation improves follicular microenviroment in poor responder patients''.<ref><pubmed>22835219</pubmed></ref> This study looked at a group of 24 women aged between 31 and 42 diagnosed with poor ovarian response (POR) in which fewer follicles properly develop. These women were randomly split into two groups; one of which received no special treatment prior to IVF, while the other group received dehydroepiandrosterone (DHEA) supplementation, which was hypothesised to increase the quality of the oocytes and therefore increase the chance of a successful pregnancy.

The results showed that the group of women that received DHEA supplementation prior to IVF had lower levels of HIF1 in their follicular fluid; a substance produced by the body in response to low oxygen levels. This suggests that DHEA increases the supply of oxygen to the developing follicle and thus increases its quality, as it had been previously shown that oxygen plays a very important role in follicle development. Although the study demonstrated with statistical significance that supplementation with DHEA led to higher levels of HIF1, it could not be shown that supplementation led to better IVF outcomes, however this was attributed to the small sample size. The study concluded that DHEA supplementation is a viable option to increasing follicle development in women with POR as it is relatively cheap, easily administered and has minimal side effects.

==Lab 2 Assessment==

[[File:Macaque Oocyte.jpg|200px|thumb|left|A recently fertilised macaque oocyte.<ref><pubmed>20591337</pubmed></ref>]]

'''1. Upload an image from a journal source relating to fertilization or the first 2 weeks of development as demonstrated in the practical class. Including in the image “Summary” window: An image name as a section heading, Any further description of what the image shows, A subsection labeled “Reference” and under this the original image source, appropriate reference and all copyright information and finally a template indicating that this is a student image. {{Template:Student Image}}'''

The image to the left is from a journal article that investigated both in vivo and in vitro fertilisation in the macaque monkey. It shows a macaque oocyte containing both the maternal and paternal pronuclei. The link to this article can be found both below in 'references' and also in the description of the image.

'''2. Identify a protein associated with the implantation process, including a brief description of the protein's role.
'''

A protein associated with the implantation process is the glycoprotein ''fibronectin.'' It is involved in cell adhesion, growth, migration and differentiation; making it important in many bodily processes including wound healing and embryo implantation. In implantation, it guides cell attachment and migration, and the absence of fibronectin leads to defects in mesodermal, neural tube and vascular development; causing early embryo death.<ref>http://en.wikipedia.org/wiki/Fibronectin</ref>

==Lab 3 Assessment==

'''1. Identify the difference between "gestational age" and "post-fertilisation age" and explain why clinically "gestational age" is used in describing human development.'''

Gestational age is the time that has elapsed since the pregnant woman's last menstrual period began, measured in weeks. Post-fertilisation age is the time that has elapsed since the oocyte was fertilised by the sperm, also measured in weeks. Fertilisation reliably occurs 2 weeks after the last menstrual period, so gestational age is roughly 2 weeks greater than the post-fertilisation age. Gestational age is used clinically to describe human development as it is often difficult to identify the precise timing of fertilisation, thus the time since the last menstrual period (gestational age) is more convenient. Using gestational age, a pregnancy can be identified as premature or postmature. This identification has implications for a successful birth, as premature babies have a greater risk of complications and death.<ref>http://en.wikipedia.org/wiki/Gestational_age</ref>

'''2. Identify using histological descriptions at least 3 different types of tissues formed from somites.'''

Three different types of tissues formed from somites include the dermis (from dermatomes), skeletal muscle (from myotomes) and bone (from sclerotomes). Histologically, the dermis is an area of connective tissue under the outer, keratinised epidermis, that contains blood vessels and nerve endings. Skeletal muscle is muscle that appears striated and is under voluntary control by the nervous system. Bone is a specialised form of connective tissue that is organised into compact and spongy forms. The compact components provide rigidity while spongy bone works to distribute loads across the bone.<ref>http://en.wikipedia.org/wiki/Somite</ref>

==Lab 4 Assessment==

'''1. Identify the 2 invasive prenatal diagnostic techniques related to the placenta and 2 abnormalities that can be identified with these techniques.'''

An invasive prenatal diagnostic technique related to the placenta is an amniocentesis. This involves inserting a needle through the mother's abdomen and collecting a sample of the amniotic fluid, which contains cells shed by the fetus. Through analysis, this technique can identify chromosomal disorders such as Down syndrome as well as open neural tube defects such as spina bifida.<ref>http://www.knowyourgenes.org/prenatal_testing.shtml</ref>

Another invasive prenatal diagnostic technique is chorionic villus sampling (CVS). This involves inserting a catheter through the cervix and removing a small sample of placental tissue, which has the same genetic material as the fetus. This can then be tested for chromosomal abnormalities like Down syndrome, however cannot detect neural tube defects such as spina bifida, which an amniocentesis can detect.<ref>http://www.hopkinsmedicine.org/healthlibrary/conditions/a/pregnancy_and_childbirth/common_tests_during_pregnancy_85,P01241/</ref>

'''2. Identify a paper that uses cord stem cells therapeutically and write a brief (2-3 paragraph) description of the paper's findings.'''

A paper that uses umbilical cord stem cells therapeutically is one from a group of researchers at Seoul National University in South Korea entitled ''Comparison of Mesenchymal Stem Cells Derived from Fat, Bone Marrow, Wharton's Jelly, and Umbilical Cord Blood for Treating Spinal Cord Injuries in Dogs.''<ref><pubmed>22878503</pubmed></ref> They induced spinal cord injuries in dogs through the use of balloon catheter compression and then applied stem cells from a variety of sources to the site of injury and compared the recovery that was achieved between the different groups.

It was found that all stem cell treatments produced significant improvements in locomotion at 8 weeks after implantation, and that this was accompanied by increased numbers of neurons and neurofilament-positive fibers at the lesion site. However it was also found that even though the umbilical cord stem cells produced no greater improvement in locomotion than the other stem cells, the umbilical cord stem cells produced more nerve regeneration and anti-inflammation activity.

==Lab 5 Assessment==

'''Completing the in class Quiz!'''

==Lab 6 Assessment==

'''To Be added.'''

==Lab 7 Assessment==

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

A muscle satellite cell is a mononuclear progenitor cell containing very little cytoplasm found between muscle fibres.

Two examples of when satellite cells are activated occur during normal muscle growth and when the muscle is damaged. In both cases, under mechanical strain the satellite cells are activated and either form new muscle fibres or fuse to existing muscle fibres to make them larger.<ref>http://en.wikipedia.org/wiki/Myosatellite_cell</ref>

==Lab 8 Assessment==

'''Individual assessment this week relates to your group project.'''

'''1. Each student should now look at each of the other Group projects in the class.'''

'''2. Next prepare a critical assessment (should include both positive and negative issues) of each project using the project assessment criteria.'''

'''3. This assessment should be pasted without signature on the top of the specific project's discussion page (minimum length 3-5 paragraphs/project).'''

'''4. This critical assessment should also be pasted on your own student page. Each student should therefore have 5 separate reports pasted on their own page for this assessment item. Length, quality and accuracy of your reports will be part of the overall mark for this assessment (there will be a greater loading on this than simple question assessments).'''

'''Somatosensory'''

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.

----

'''Taste'''

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.

----

'''Olfaction'''

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.

----

'''Abnormal Vision'''

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.

----

'''Hearing'''

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.

==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.'''

A recent research paper on the development of the pancreas is one from 2000 (getting a bit old now, I suppose) entitled ''Regulation of pancreas development by hedgehog signaling.''<ref><pubmed>11044404</pubmed></ref> In this paper, the researchers investigated the effect that the factors Sonic hedgehog, Indian hedgehog and Patched 1 have on development of the pancreas by observing the effect that mutations leading to the absence of these factors have on the organism. They found that Sonic hedgehog represses the growth of the pancreas and is important in limiting its size. For example, if the tissues surrounding the pancreas are not expressing Sonic hedgehog, then the pancreas will grow uncontrollably up to three times its usual mass with much more pancreatic islets than usual, thus impairing the normal functioning of the tissues around it including the stomach and duodenum. They also found that Indian hedgehog plays a different role than Sonic, in that it is required for normal growth rather than repressing growth. In organisms where Sonic was absent along with Indian, there was no observed abnormally large growth, as seen when Sonic was absent but Indian was present. Finally, it was also concluded that without Patched 1, the pancreas is unable to maintain glucose homeostasis.

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

The developing teeth are composed of neural crest-derived mesenchyme and ectoderm from the first pharyngeal arch. Inductive processes occur between these two embryonic tissue types at week 6 to produce the first sign of teeth (teeth buds) in a process known as odontogenesis.<ref><pubmed>19266065</pubmed></ref>

==References==

<references/>

Talk:2012 Group Project 1

2012-10-02T23:47:43Z

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{{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.

-------

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)

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Vision

Overall the information presented is clear and concise. The development section is well researched and provides information of each individual part of the eye. The introduction is very brief and needs more on the development of the eye (as the project is on the development part. I feel that the anatomy should be under a separate heading. It also has two images that the serve essentially the same purpose. The historical section needs more on recent discoveries not just ancient ones. More work needs to be done on the layout of the images as is often hard to determine which image relates to which text. For the current research section, I think the group would benefit if they give a summary of the research as opposed to just listing the articles.

== 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)

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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)

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Hey there is some good info for the '''history''' section in this article: http://www.ncbi.nlm.nih.gov/pubmed/1100417 --[[User:Z3373894|Z3373894]] 17:42, 27 September 2012 (EST)

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Wow the research history looks so good! Good research :D --[[User:Z3373894|Z3373894]] 08:24, 2 October 2012 (EST)

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...and the current research :) nice work guys, page looks good! --[[User:Z3373894|Z3373894]] 09:47, 3 October 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>
<pubmed>1100417</pubmed>
<pubmed>9216064</pubmed>

--[[User:Z3254758|Z3254758]] 17:58, 4 September 2012 (EST) --[[User:Z3373894|Z3373894]] 17:44, 27 September 2012 (EST)

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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)

2012 Group Project 1

2012-10-02T23:41:51Z

Z3373894: /* 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<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===

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).

---------

===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>

{| 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.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

2012-10-02T23:26:23Z

Z3373894: /* Activation of c-Jun N-terminal kinase (JNK) during mitosis in retinal progenitor 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 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).

---------

===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]- 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
|-
| 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.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

2012-10-02T23:21:54Z

Z3373894: /* LRP5 is required for vascular development in deeper layers of the retina */

[[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===

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).

---------

===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]- 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
|-
| 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 was 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.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

2012-10-02T23:17:22Z

Z3373894:

[[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===

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).

---------

===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]- 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
|-
| 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 was 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 “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}}

2012 Group Project 1

2012-10-02T23:15:01Z

Z3373894:

[[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===

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).

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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]- 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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===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 was 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 “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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===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.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}}

User:Z3373894

2012-10-02T07:10:41Z

Z3373894: /* Lab 4 Assessment */

==Lab Attendance==

Lab 1 -- [[User:Z3373894|Z3373894]] 11:49, 25 July 2012 (EST)

Lab 2 -- [[User:Z3373894|Z3373894]] 10:37, 1 August 2012 (EST)

Lab 3 -- [[User:Z3373894|Z3373894]] 10:06, 8 August 2012 (EST)

Lab 4 -- [[User:Z3373894|Z3373894]] 10:23, 15 August 2012 (EST)

Lab 5 -- [[User:Z3373894|Z3373894]] 10:05, 22 August 2012 (EST)

Lab 6 -- [[User:Z3373894|Z3373894]] 10:02, 29 August 2012 (EST)

Lab 7 -- [[User:Z3373894|Z3373894]] 10:14, 12 September 2012 (EST)

Lab 8 -- Attended lab but forgot to sign attendance. Sorry!

Lab 9 -- [[User:Z3373894|Z3373894]] 10:02, 26 September 2012 (EST)

==Lab 1 Assessment==

'''1. Identify the origin of In Vitro Fertilization and the 2010 nobel prize winner associated with this technique and add a correctly formatted link to the Nobel page.'''

In vitro fertilisation (IVF) has its origins in the 1970s, specifically 1978 when the first successful birth of an IVF baby occurred. This birth was the result of the work of physiologist [http://www.nobelprize.org/nobel_prizes/medicine/laureates/2010/edwards.html Robert G. Edwards], who developed the technique and subsequently won the [http://www.nobelprize.org/nobel_prizes/medicine/laureates/2010/ Nobel Prize in Physiology or Medicine 2010] for his work. The procedure involves removing a healthy ovum from the mother and fertilising it outside of the female's body, where the term ''in vitro'', which is Latin for "in glass" comes from. Today, this term is used to describe any procedure that takes place outside of the body, in opposition to an ''in vivo'' procedure which takes place inside the body. The zygote is then implanted back into the woman's uterus where it can develop normally.<ref>http://en.wikipedia.org/wiki/In_vitro_fertilisation</ref>

'''2. Identify and add a PubMed reference link to a recent paper on fertilisation and describe its key findings (1-2 paragraphs).'''

A recent paper published on the topic of fertilisation includes a paper from researchers at the University of Pisa in Italy entitled ''DHEA supplementation improves follicular microenviroment in poor responder patients''.<ref><pubmed>22835219</pubmed></ref> This study looked at a group of 24 women aged between 31 and 42 diagnosed with poor ovarian response (POR) in which fewer follicles properly develop. These women were randomly split into two groups; one of which received no special treatment prior to IVF, while the other group received dehydroepiandrosterone (DHEA) supplementation, which was hypothesised to increase the quality of the oocytes and therefore increase the chance of a successful pregnancy.

The results showed that the group of women that received DHEA supplementation prior to IVF had lower levels of HIF1 in their follicular fluid; a substance produced by the body in response to low oxygen levels. This suggests that DHEA increases the supply of oxygen to the developing follicle and thus increases its quality, as it had been previously shown that oxygen plays a very important role in follicle development. Although the study demonstrated with statistical significance that supplementation with DHEA led to higher levels of HIF1, it could not be shown that supplementation led to better IVF outcomes, however this was attributed to the small sample size. The study concluded that DHEA supplementation is a viable option to increasing follicle development in women with POR as it is relatively cheap, easily administered and has minimal side effects.

==Lab 2 Assessment==

[[File:Macaque Oocyte.jpg|200px|thumb|left|A recently fertilised macaque oocyte.<ref><pubmed>20591337</pubmed></ref>]]

'''1. Upload an image from a journal source relating to fertilization or the first 2 weeks of development as demonstrated in the practical class. Including in the image “Summary” window: An image name as a section heading, Any further description of what the image shows, A subsection labeled “Reference” and under this the original image source, appropriate reference and all copyright information and finally a template indicating that this is a student image. {{Template:Student Image}}'''

The image to the left is from a journal article that investigated both in vivo and in vitro fertilisation in the macaque monkey. It shows a macaque oocyte containing both the maternal and paternal pronuclei. The link to this article can be found both below in 'references' and also in the description of the image.

'''2. Identify a protein associated with the implantation process, including a brief description of the protein's role.
'''

A protein associated with the implantation process is the glycoprotein ''fibronectin.'' It is involved in cell adhesion, growth, migration and differentiation; making it important in many bodily processes including wound healing and embryo implantation. In implantation, it guides cell attachment and migration, and the absence of fibronectin leads to defects in mesodermal, neural tube and vascular development; causing early embryo death.<ref>http://en.wikipedia.org/wiki/Fibronectin</ref>

==Lab 3 Assessment==

'''1. Identify the difference between "gestational age" and "post-fertilisation age" and explain why clinically "gestational age" is used in describing human development.'''

Gestational age is the time that has elapsed since the pregnant woman's last menstrual period began, measured in weeks. Post-fertilisation age is the time that has elapsed since the oocyte was fertilised by the sperm, also measured in weeks. Fertilisation reliably occurs 2 weeks after the last menstrual period, so gestational age is roughly 2 weeks greater than the post-fertilisation age. Gestational age is used clinically to describe human development as it is often difficult to identify the precise timing of fertilisation, thus the time since the last menstrual period (gestational age) is more convenient. Using gestational age, a pregnancy can be identified as premature or postmature. This identification has implications for a successful birth, as premature babies have a greater risk of complications and death.<ref>http://en.wikipedia.org/wiki/Gestational_age</ref>

'''2. Identify using histological descriptions at least 3 different types of tissues formed from somites.'''

Three different types of tissues formed from somites include the dermis (from dermatomes), skeletal muscle (from myotomes) and bone (from sclerotomes). Histologically, the dermis is an area of connective tissue under the outer, keratinised epidermis, that contains blood vessels and nerve endings. Skeletal muscle is muscle that appears striated and is under voluntary control by the nervous system. Bone is a specialised form of connective tissue that is organised into compact and spongy forms. The compact components provide rigidity while spongy bone works to distribute loads across the bone.<ref>http://en.wikipedia.org/wiki/Somite</ref>

==Lab 4 Assessment==

'''1. Identify the 2 invasive prenatal diagnostic techniques related to the placenta and 2 abnormalities that can be identified with these techniques.'''

An invasive prenatal diagnostic technique related to the placenta is an amniocentesis. This involves inserting a needle through the mother's abdomen and collecting a sample of the amniotic fluid, which contains cells shed by the fetus. Through analysis, this technique can identify chromosomal disorders such as Down syndrome as well as open neural tube defects such as spina bifida.<ref>http://www.knowyourgenes.org/prenatal_testing.shtml</ref>

Another invasive prenatal diagnostic technique is chorionic villus sampling (CVS). This involves inserting a catheter through the cervix and removing a small sample of placental tissue, which has the same genetic material as the fetus. This can then be tested for chromosomal abnormalities like Down syndrome, however cannot detect neural tube defects such as spina bifida, which an amniocentesis can detect.<ref>http://www.hopkinsmedicine.org/healthlibrary/conditions/a/pregnancy_and_childbirth/common_tests_during_pregnancy_85,P01241/</ref>

'''2. Identify a paper that uses cord stem cells therapeutically and write a brief (2-3 paragraph) description of the paper's findings.'''

A paper that uses umbilical cord stem cells therapeutically is one from a group of researchers at Seoul National University in South Korea entitled ''Comparison of Mesenchymal Stem Cells Derived from Fat, Bone Marrow, Wharton's Jelly, and Umbilical Cord Blood for Treating Spinal Cord Injuries in Dogs.''<ref><pubmed>22878503</pubmed></ref> They induced spinal cord injuries in dogs through the use of balloon catheter compression and then applied stem cells from a variety of sources to the site of injury and compared the recovery that was achieved between the different groups.

It was found that all stem cell treatments produced significant improvements in locomotion at 8 weeks after implantation, and that this was accompanied by increased numbers of neurons and neurofilament-positive fibers at the lesion site. However it was also found that even though the umbilical cord stem cells produced no greater improvement in locomotion than the other stem cells, the umbilical cord stem cells produced more nerve regeneration and anti-inflammation activity.

==Lab 5 Assessment==

'''Completing the in class Quiz!'''

==Lab 6 Assessment==

'''To Be added.'''

==Lab 7 Assessment==

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

A muscle satellite cell is a mononuclear progenitor cell containing very little cytoplasm found between muscle fibres.

Two examples of when satellite cells are activated occur during normal muscle growth and when the muscle is damaged. In both cases, under mechanical strain the satellite cells are activated and either form new muscle fibres or fuse to existing muscle fibres to make them larger.<ref>http://en.wikipedia.org/wiki/Myosatellite_cell</ref>

==Lab 8 Assessment==

'''Individual assessment this week relates to your group project.'''

'''1. Each student should now look at each of the other Group projects in the class.'''

'''2. Next prepare a critical assessment (should include both positive and negative issues) of each project using the project assessment criteria.'''

'''3. This assessment should be pasted without signature on the top of the specific project's discussion page (minimum length 3-5 paragraphs/project).'''

'''4. This critical assessment should also be pasted on your own student page. Each student should therefore have 5 separate reports pasted on their own page for this assessment item. Length, quality and accuracy of your reports will be part of the overall mark for this assessment (there will be a greater loading on this than simple question assessments).'''

'''Somatosensory'''

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.

----

'''Taste'''

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.

----

'''Olfaction'''

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.

----

'''Abnormal Vision'''

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.

----

'''Hearing'''

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.

==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.'''

A recent research paper on the development of the pancreas is one from 2000 (getting a bit old now, I suppose) entitled ''Regulation of pancreas development by hedgehog signaling.''<ref><pubmed>11044404</pubmed></ref> In this paper, the researchers investigated the effect that the factors Sonic hedgehog, Indian hedgehog and Patched 1 have on development of the pancreas by observing the effect that mutations leading to the absence of these factors have on the organism. They found that Sonic hedgehog represses the growth of the pancreas and is important in limiting its size. For example, if the tissues surrounding the pancreas are not expressing Sonic hedgehog, then the pancreas will grow uncontrollably up to three times its usual mass with much more pancreatic islets than usual, thus impairing the normal functioning of the tissues around it including the stomach and duodenum. They also found that Indian hedgehog plays a different role than Sonic, in that it is required for normal growth rather than repressing growth. In organisms where Sonic was absent along with Indian, there was no observed abnormally large growth, as seen when Sonic was absent but Indian was present. Finally, it was also concluded that without Patched 1, the pancreas is unable to maintain glucose homeostasis.

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

The developing teeth are composed of neural crest-derived mesenchyme and ectoderm from the first pharyngeal arch. Inductive processes occur between these two embryonic tissue types at week 6 to produce the first sign of teeth (teeth buds) in a process known as odontogenesis.<ref><pubmed>19266065</pubmed></ref>

==References==

<references/>

User:Z3373894

2012-10-02T07:08:50Z

Z3373894: /* Lab 9 Assessment */

==Lab Attendance==

Lab 1 -- [[User:Z3373894|Z3373894]] 11:49, 25 July 2012 (EST)

Lab 2 -- [[User:Z3373894|Z3373894]] 10:37, 1 August 2012 (EST)

Lab 3 -- [[User:Z3373894|Z3373894]] 10:06, 8 August 2012 (EST)

Lab 4 -- [[User:Z3373894|Z3373894]] 10:23, 15 August 2012 (EST)

Lab 5 -- [[User:Z3373894|Z3373894]] 10:05, 22 August 2012 (EST)

Lab 6 -- [[User:Z3373894|Z3373894]] 10:02, 29 August 2012 (EST)

Lab 7 -- [[User:Z3373894|Z3373894]] 10:14, 12 September 2012 (EST)

Lab 8 -- Attended lab but forgot to sign attendance. Sorry!

Lab 9 -- [[User:Z3373894|Z3373894]] 10:02, 26 September 2012 (EST)

==Lab 1 Assessment==

'''1. Identify the origin of In Vitro Fertilization and the 2010 nobel prize winner associated with this technique and add a correctly formatted link to the Nobel page.'''

In vitro fertilisation (IVF) has its origins in the 1970s, specifically 1978 when the first successful birth of an IVF baby occurred. This birth was the result of the work of physiologist [http://www.nobelprize.org/nobel_prizes/medicine/laureates/2010/edwards.html Robert G. Edwards], who developed the technique and subsequently won the [http://www.nobelprize.org/nobel_prizes/medicine/laureates/2010/ Nobel Prize in Physiology or Medicine 2010] for his work. The procedure involves removing a healthy ovum from the mother and fertilising it outside of the female's body, where the term ''in vitro'', which is Latin for "in glass" comes from. Today, this term is used to describe any procedure that takes place outside of the body, in opposition to an ''in vivo'' procedure which takes place inside the body. The zygote is then implanted back into the woman's uterus where it can develop normally.<ref>http://en.wikipedia.org/wiki/In_vitro_fertilisation</ref>

'''2. Identify and add a PubMed reference link to a recent paper on fertilisation and describe its key findings (1-2 paragraphs).'''

A recent paper published on the topic of fertilisation includes a paper from researchers at the University of Pisa in Italy entitled ''DHEA supplementation improves follicular microenviroment in poor responder patients''.<ref><pubmed>22835219</pubmed></ref> This study looked at a group of 24 women aged between 31 and 42 diagnosed with poor ovarian response (POR) in which fewer follicles properly develop. These women were randomly split into two groups; one of which received no special treatment prior to IVF, while the other group received dehydroepiandrosterone (DHEA) supplementation, which was hypothesised to increase the quality of the oocytes and therefore increase the chance of a successful pregnancy.

The results showed that the group of women that received DHEA supplementation prior to IVF had lower levels of HIF1 in their follicular fluid; a substance produced by the body in response to low oxygen levels. This suggests that DHEA increases the supply of oxygen to the developing follicle and thus increases its quality, as it had been previously shown that oxygen plays a very important role in follicle development. Although the study demonstrated with statistical significance that supplementation with DHEA led to higher levels of HIF1, it could not be shown that supplementation led to better IVF outcomes, however this was attributed to the small sample size. The study concluded that DHEA supplementation is a viable option to increasing follicle development in women with POR as it is relatively cheap, easily administered and has minimal side effects.

==Lab 2 Assessment==

[[File:Macaque Oocyte.jpg|200px|thumb|left|A recently fertilised macaque oocyte.<ref><pubmed>20591337</pubmed></ref>]]

'''1. Upload an image from a journal source relating to fertilization or the first 2 weeks of development as demonstrated in the practical class. Including in the image “Summary” window: An image name as a section heading, Any further description of what the image shows, A subsection labeled “Reference” and under this the original image source, appropriate reference and all copyright information and finally a template indicating that this is a student image. {{Template:Student Image}}'''

The image to the left is from a journal article that investigated both in vivo and in vitro fertilisation in the macaque monkey. It shows a macaque oocyte containing both the maternal and paternal pronuclei. The link to this article can be found both below in 'references' and also in the description of the image.

'''2. Identify a protein associated with the implantation process, including a brief description of the protein's role.
'''

A protein associated with the implantation process is the glycoprotein ''fibronectin.'' It is involved in cell adhesion, growth, migration and differentiation; making it important in many bodily processes including wound healing and embryo implantation. In implantation, it guides cell attachment and migration, and the absence of fibronectin leads to defects in mesodermal, neural tube and vascular development; causing early embryo death.<ref>http://en.wikipedia.org/wiki/Fibronectin</ref>

==Lab 3 Assessment==

'''1. Identify the difference between "gestational age" and "post-fertilisation age" and explain why clinically "gestational age" is used in describing human development.'''

Gestational age is the time that has elapsed since the pregnant woman's last menstrual period began, measured in weeks. Post-fertilisation age is the time that has elapsed since the oocyte was fertilised by the sperm, also measured in weeks. Fertilisation reliably occurs 2 weeks after the last menstrual period, so gestational age is roughly 2 weeks greater than the post-fertilisation age. Gestational age is used clinically to describe human development as it is often difficult to identify the precise timing of fertilisation, thus the time since the last menstrual period (gestational age) is more convenient. Using gestational age, a pregnancy can be identified as premature or postmature. This identification has implications for a successful birth, as premature babies have a greater risk of complications and death.<ref>http://en.wikipedia.org/wiki/Gestational_age</ref>

'''2. Identify using histological descriptions at least 3 different types of tissues formed from somites.'''

Three different types of tissues formed from somites include the dermis (from dermatomes), skeletal muscle (from myotomes) and bone (from sclerotomes). Histologically, the dermis is an area of connective tissue under the outer, keratinised epidermis, that contains blood vessels and nerve endings. Skeletal muscle is muscle that appears striated and is under voluntary control by the nervous system. Bone is a specialised form of connective tissue that is organised into compact and spongy forms. The compact components provide rigidity while spongy bone works to distribute loads across the bone.<ref>http://en.wikipedia.org/wiki/Somite</ref>

==Lab 4 Assessment==

'''1. Identify the 2 invasive prenatal diagnostic techniques related to the placenta and 2 abnormalities that can be identified with these techniques.'''

An invasive prenatal diagnostic technique related to the placenta is an amniocentesis. This involves inserting a needle through the mother's abdomen and collecting a sample of the amniotic fluid, which contains cells shed by the fetus. Through analysis, this technique can identify chromosomal disorders such as Down syndrome as well as open neural tube defects such as spina bifida.<ref>http://www.knowyourgenes.org/prenatal_testing.shtml</ref>

Another invasive prenatal diagnostic technique is chorionic villus sampling (CVS). This involves inserting a catheter through the cervix and removing a small sample of placental tissue, which has the same genetic material as the fetus. This can then be tested for chromosomal abnormalities like Down syndrome, however cannot detect neural tube defects such as spina bifida, which an amniocentesis can detect.<ref>http://www.hopkinsmedicine.org/healthlibrary/conditions/a/pregnancy_and_childbirth/common_tests_during_pregnancy_85,P01241/</ref>

'''2. Identify a paper that uses cord stem cells therapeutically and write a brief (2-3 paragraph) description of the paper's findings.'''

A paper that uses umbilical cord stem cells therapeutically is one from a group of researchers at Seoul National University in South Korea entitled ''Comparison of Mesenchymal Stem Cells Derived from Fat, Bone Marrow, Wharton's Jelly, and Umbilical Cord Blood for Treating Spinal Cord Injuries in Dogs.''<ref><pubmed>22878503</pubmed></ref> They induced spinal cord injuries in dogs through the use of balloon catheter compression and then applied stem cells from a variety of sources to the site of injury and compared the recovery that was achieved between the different groups.

It was found that all stem cell treatments produced significant improvements in locomotion at 8 weeks after implantation, and that this was accompanied by increased numbers of neurons and neurofilament-positive fibers at the lesion site. However it was also found that even though the umbilical cord stem cells produced no greater improvement in locomotion than the other stem cells, the umbilical cord stem cells produced more nerve regeneration and anti-inflammation activity.

==Lab 5 Assessment==

'''Completing the in class Quiz!'''

==Lab 6 Assessment==

'''To Be added.'''

==Lab 7 Assessment==

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

A muscle satellite cell is a mononuclear progenitor cell containing very little cytoplasm found between muscle fibres.

Two examples of when satellite cells are activated occur during normal muscle growth and when the muscle is damaged. In both cases, under mechanical strain the satellite cells are activated and either form new muscle fibres or fuse to existing muscle fibres to make them larger.<ref>http://en.wikipedia.org/wiki/Myosatellite_cell</ref>

==Lab 8 Assessment==

'''Individual assessment this week relates to your group project.'''

'''1. Each student should now look at each of the other Group projects in the class.'''

'''2. Next prepare a critical assessment (should include both positive and negative issues) of each project using the project assessment criteria.'''

'''3. This assessment should be pasted without signature on the top of the specific project's discussion page (minimum length 3-5 paragraphs/project).'''

'''4. This critical assessment should also be pasted on your own student page. Each student should therefore have 5 separate reports pasted on their own page for this assessment item. Length, quality and accuracy of your reports will be part of the overall mark for this assessment (there will be a greater loading on this than simple question assessments).'''

'''Somatosensory'''

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.

----

'''Taste'''

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.

----

'''Olfaction'''

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.

----

'''Abnormal Vision'''

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.

----

'''Hearing'''

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.

==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.'''

A recent research paper on the development of the pancreas is one from 2000 (getting a bit old now, I suppose) entitled ''Regulation of pancreas development by hedgehog signaling.''<ref><pubmed>11044404</pubmed></ref> In this paper, the researchers investigated the effect that the factors Sonic hedgehog, Indian hedgehog and Patched 1 have on development of the pancreas by observing the effect that mutations leading to the absence of these factors have on the organism. They found that Sonic hedgehog represses the growth of the pancreas and is important in limiting its size. For example, if the tissues surrounding the pancreas are not expressing Sonic hedgehog, then the pancreas will grow uncontrollably up to three times its usual mass with much more pancreatic islets than usual, thus impairing the normal functioning of the tissues around it including the stomach and duodenum. They also found that Indian hedgehog plays a different role than Sonic, in that it is required for normal growth rather than repressing growth. In organisms where Sonic was absent along with Indian, there was no observed abnormally large growth, as seen when Sonic was absent but Indian was present. Finally, it was also concluded that without Patched 1, the pancreas is unable to maintain glucose homeostasis.

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

The developing teeth are composed of neural crest-derived mesenchyme and ectoderm from the first pharyngeal arch. Inductive processes occur between these two embryonic tissue types at week 6 to produce the first sign of teeth (teeth buds) in a process known as odontogenesis.<ref><pubmed>19266065</pubmed></ref>

==References==

<references/>

User:Z3373894

2012-10-02T07:05:41Z

Z3373894: /* Lab 9 Assessment */

==Lab Attendance==

Lab 1 -- [[User:Z3373894|Z3373894]] 11:49, 25 July 2012 (EST)

Lab 2 -- [[User:Z3373894|Z3373894]] 10:37, 1 August 2012 (EST)

Lab 3 -- [[User:Z3373894|Z3373894]] 10:06, 8 August 2012 (EST)

Lab 4 -- [[User:Z3373894|Z3373894]] 10:23, 15 August 2012 (EST)

Lab 5 -- [[User:Z3373894|Z3373894]] 10:05, 22 August 2012 (EST)

Lab 6 -- [[User:Z3373894|Z3373894]] 10:02, 29 August 2012 (EST)

Lab 7 -- [[User:Z3373894|Z3373894]] 10:14, 12 September 2012 (EST)

Lab 8 -- Attended lab but forgot to sign attendance. Sorry!

Lab 9 -- [[User:Z3373894|Z3373894]] 10:02, 26 September 2012 (EST)

==Lab 1 Assessment==

'''1. Identify the origin of In Vitro Fertilization and the 2010 nobel prize winner associated with this technique and add a correctly formatted link to the Nobel page.'''

In vitro fertilisation (IVF) has its origins in the 1970s, specifically 1978 when the first successful birth of an IVF baby occurred. This birth was the result of the work of physiologist [http://www.nobelprize.org/nobel_prizes/medicine/laureates/2010/edwards.html Robert G. Edwards], who developed the technique and subsequently won the [http://www.nobelprize.org/nobel_prizes/medicine/laureates/2010/ Nobel Prize in Physiology or Medicine 2010] for his work. The procedure involves removing a healthy ovum from the mother and fertilising it outside of the female's body, where the term ''in vitro'', which is Latin for "in glass" comes from. Today, this term is used to describe any procedure that takes place outside of the body, in opposition to an ''in vivo'' procedure which takes place inside the body. The zygote is then implanted back into the woman's uterus where it can develop normally.<ref>http://en.wikipedia.org/wiki/In_vitro_fertilisation</ref>

'''2. Identify and add a PubMed reference link to a recent paper on fertilisation and describe its key findings (1-2 paragraphs).'''

A recent paper published on the topic of fertilisation includes a paper from researchers at the University of Pisa in Italy entitled ''DHEA supplementation improves follicular microenviroment in poor responder patients''.<ref><pubmed>22835219</pubmed></ref> This study looked at a group of 24 women aged between 31 and 42 diagnosed with poor ovarian response (POR) in which fewer follicles properly develop. These women were randomly split into two groups; one of which received no special treatment prior to IVF, while the other group received dehydroepiandrosterone (DHEA) supplementation, which was hypothesised to increase the quality of the oocytes and therefore increase the chance of a successful pregnancy.

The results showed that the group of women that received DHEA supplementation prior to IVF had lower levels of HIF1 in their follicular fluid; a substance produced by the body in response to low oxygen levels. This suggests that DHEA increases the supply of oxygen to the developing follicle and thus increases its quality, as it had been previously shown that oxygen plays a very important role in follicle development. Although the study demonstrated with statistical significance that supplementation with DHEA led to higher levels of HIF1, it could not be shown that supplementation led to better IVF outcomes, however this was attributed to the small sample size. The study concluded that DHEA supplementation is a viable option to increasing follicle development in women with POR as it is relatively cheap, easily administered and has minimal side effects.

==Lab 2 Assessment==

[[File:Macaque Oocyte.jpg|200px|thumb|left|A recently fertilised macaque oocyte.<ref><pubmed>20591337</pubmed></ref>]]

'''1. Upload an image from a journal source relating to fertilization or the first 2 weeks of development as demonstrated in the practical class. Including in the image “Summary” window: An image name as a section heading, Any further description of what the image shows, A subsection labeled “Reference” and under this the original image source, appropriate reference and all copyright information and finally a template indicating that this is a student image. {{Template:Student Image}}'''

The image to the left is from a journal article that investigated both in vivo and in vitro fertilisation in the macaque monkey. It shows a macaque oocyte containing both the maternal and paternal pronuclei. The link to this article can be found both below in 'references' and also in the description of the image.

'''2. Identify a protein associated with the implantation process, including a brief description of the protein's role.
'''

A protein associated with the implantation process is the glycoprotein ''fibronectin.'' It is involved in cell adhesion, growth, migration and differentiation; making it important in many bodily processes including wound healing and embryo implantation. In implantation, it guides cell attachment and migration, and the absence of fibronectin leads to defects in mesodermal, neural tube and vascular development; causing early embryo death.<ref>http://en.wikipedia.org/wiki/Fibronectin</ref>

==Lab 3 Assessment==

'''1. Identify the difference between "gestational age" and "post-fertilisation age" and explain why clinically "gestational age" is used in describing human development.'''

Gestational age is the time that has elapsed since the pregnant woman's last menstrual period began, measured in weeks. Post-fertilisation age is the time that has elapsed since the oocyte was fertilised by the sperm, also measured in weeks. Fertilisation reliably occurs 2 weeks after the last menstrual period, so gestational age is roughly 2 weeks greater than the post-fertilisation age. Gestational age is used clinically to describe human development as it is often difficult to identify the precise timing of fertilisation, thus the time since the last menstrual period (gestational age) is more convenient. Using gestational age, a pregnancy can be identified as premature or postmature. This identification has implications for a successful birth, as premature babies have a greater risk of complications and death.<ref>http://en.wikipedia.org/wiki/Gestational_age</ref>

'''2. Identify using histological descriptions at least 3 different types of tissues formed from somites.'''

Three different types of tissues formed from somites include the dermis (from dermatomes), skeletal muscle (from myotomes) and bone (from sclerotomes). Histologically, the dermis is an area of connective tissue under the outer, keratinised epidermis, that contains blood vessels and nerve endings. Skeletal muscle is muscle that appears striated and is under voluntary control by the nervous system. Bone is a specialised form of connective tissue that is organised into compact and spongy forms. The compact components provide rigidity while spongy bone works to distribute loads across the bone.<ref>http://en.wikipedia.org/wiki/Somite</ref>

==Lab 4 Assessment==

'''1. Identify the 2 invasive prenatal diagnostic techniques related to the placenta and 2 abnormalities that can be identified with these techniques.'''

An invasive prenatal diagnostic technique related to the placenta is an amniocentesis. This involves inserting a needle through the mother's abdomen and collecting a sample of the amniotic fluid, which contains cells shed by the fetus. Through analysis, this technique can identify chromosomal disorders such as Down syndrome as well as open neural tube defects such as spina bifida.<ref>http://www.knowyourgenes.org/prenatal_testing.shtml</ref>

Another invasive prenatal diagnostic technique is chorionic villus sampling (CVS). This involves inserting a catheter through the cervix and removing a small sample of placental tissue, which has the same genetic material as the fetus. This can then be tested for chromosomal abnormalities like Down syndrome, however cannot detect neural tube defects such as spina bifida, which an amniocentesis can detect.<ref>http://www.hopkinsmedicine.org/healthlibrary/conditions/a/pregnancy_and_childbirth/common_tests_during_pregnancy_85,P01241/</ref>

'''2. Identify a paper that uses cord stem cells therapeutically and write a brief (2-3 paragraph) description of the paper's findings.'''

A paper that uses umbilical cord stem cells therapeutically is one from a group of researchers at Seoul National University in South Korea entitled ''Comparison of Mesenchymal Stem Cells Derived from Fat, Bone Marrow, Wharton's Jelly, and Umbilical Cord Blood for Treating Spinal Cord Injuries in Dogs.''<ref><pubmed>22878503</pubmed></ref> They induced spinal cord injuries in dogs through the use of balloon catheter compression and then applied stem cells from a variety of sources to the site of injury and compared the recovery that was achieved between the different groups.

It was found that all stem cell treatments produced significant improvements in locomotion at 8 weeks after implantation, and that this was accompanied by increased numbers of neurons and neurofilament-positive fibers at the lesion site. However it was also found that even though the umbilical cord stem cells produced no greater improvement in locomotion than the other stem cells, the umbilical cord stem cells produced more nerve regeneration and anti-inflammation activity.

==Lab 5 Assessment==

'''Completing the in class Quiz!'''

==Lab 6 Assessment==

'''To Be added.'''

==Lab 7 Assessment==

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

A muscle satellite cell is a mononuclear progenitor cell containing very little cytoplasm found between muscle fibres.

Two examples of when satellite cells are activated occur during normal muscle growth and when the muscle is damaged. In both cases, under mechanical strain the satellite cells are activated and either form new muscle fibres or fuse to existing muscle fibres to make them larger.<ref>http://en.wikipedia.org/wiki/Myosatellite_cell</ref>

==Lab 8 Assessment==

'''Individual assessment this week relates to your group project.'''

'''1. Each student should now look at each of the other Group projects in the class.'''

'''2. Next prepare a critical assessment (should include both positive and negative issues) of each project using the project assessment criteria.'''

'''3. This assessment should be pasted without signature on the top of the specific project's discussion page (minimum length 3-5 paragraphs/project).'''

'''4. This critical assessment should also be pasted on your own student page. Each student should therefore have 5 separate reports pasted on their own page for this assessment item. Length, quality and accuracy of your reports will be part of the overall mark for this assessment (there will be a greater loading on this than simple question assessments).'''

'''Somatosensory'''

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.

----

'''Taste'''

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.

----

'''Olfaction'''

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.

----

'''Abnormal Vision'''

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.

----

'''Hearing'''

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.

==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.'''

A recent research paper on the development of the pancreas is one from 2000 (getting a bit old now, I suppose) entitled ''Regulation of pancreas development by hedgehog signaling.''<ref><pubmed>11044404</pubmed></ref> In this paper, the researchers investigated the effect that the factors Sonic hedgehog, Indian hedgehog and Patched 1 have on development of the pancreas by observing the effect that mutations leading to the absence of these factors have on the organism. They found that Sonic hedgehog represses the growth of the pancreas and is important in limiting its size. For example, if the tissues surrounding the pancreas are not expressing Sonic hedgehog, then the pancreas will grow uncontrollably up to three times its usual mass with much more pancreatic islets than usual, thus impairing the normal functioning of the tissues around it including the stomach and duodenum. They also found that Indian hedgehog plays a different role than Sonic, in that it is required for normal growth rather than repressing growth. In organisms where Sonic was absent along with Indian, there was no observed abnormally large growth, as seen when Sonic was absent but Indian was present. Finally, it was also concluded that without Patched 1, the pancreas is unable to maintain glucose homeostasis.

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

The developing teeth are composed of neural crest-derived mesenchyme and ectoderm from the first pharyngeal arch. Inductive processes occur between these two embryonic tissue types at week 6 to produce the first sign of teeth (teeth buds) in a process known as odontogenesis.<ref>http://embryology.med.unsw.edu.au/embryology/index.php?title=ANAT2341_Lab_9</ref>

==References==

<references/>

User:Z3373894

2012-10-02T07:01:36Z

Z3373894:

==Lab Attendance==

Lab 1 -- [[User:Z3373894|Z3373894]] 11:49, 25 July 2012 (EST)

Lab 2 -- [[User:Z3373894|Z3373894]] 10:37, 1 August 2012 (EST)

Lab 3 -- [[User:Z3373894|Z3373894]] 10:06, 8 August 2012 (EST)

Lab 4 -- [[User:Z3373894|Z3373894]] 10:23, 15 August 2012 (EST)

Lab 5 -- [[User:Z3373894|Z3373894]] 10:05, 22 August 2012 (EST)

Lab 6 -- [[User:Z3373894|Z3373894]] 10:02, 29 August 2012 (EST)

Lab 7 -- [[User:Z3373894|Z3373894]] 10:14, 12 September 2012 (EST)

Lab 8 -- Attended lab but forgot to sign attendance. Sorry!

Lab 9 -- [[User:Z3373894|Z3373894]] 10:02, 26 September 2012 (EST)

==Lab 1 Assessment==

'''1. Identify the origin of In Vitro Fertilization and the 2010 nobel prize winner associated with this technique and add a correctly formatted link to the Nobel page.'''

In vitro fertilisation (IVF) has its origins in the 1970s, specifically 1978 when the first successful birth of an IVF baby occurred. This birth was the result of the work of physiologist [http://www.nobelprize.org/nobel_prizes/medicine/laureates/2010/edwards.html Robert G. Edwards], who developed the technique and subsequently won the [http://www.nobelprize.org/nobel_prizes/medicine/laureates/2010/ Nobel Prize in Physiology or Medicine 2010] for his work. The procedure involves removing a healthy ovum from the mother and fertilising it outside of the female's body, where the term ''in vitro'', which is Latin for "in glass" comes from. Today, this term is used to describe any procedure that takes place outside of the body, in opposition to an ''in vivo'' procedure which takes place inside the body. The zygote is then implanted back into the woman's uterus where it can develop normally.<ref>http://en.wikipedia.org/wiki/In_vitro_fertilisation</ref>

'''2. Identify and add a PubMed reference link to a recent paper on fertilisation and describe its key findings (1-2 paragraphs).'''

A recent paper published on the topic of fertilisation includes a paper from researchers at the University of Pisa in Italy entitled ''DHEA supplementation improves follicular microenviroment in poor responder patients''.<ref><pubmed>22835219</pubmed></ref> This study looked at a group of 24 women aged between 31 and 42 diagnosed with poor ovarian response (POR) in which fewer follicles properly develop. These women were randomly split into two groups; one of which received no special treatment prior to IVF, while the other group received dehydroepiandrosterone (DHEA) supplementation, which was hypothesised to increase the quality of the oocytes and therefore increase the chance of a successful pregnancy.

The results showed that the group of women that received DHEA supplementation prior to IVF had lower levels of HIF1 in their follicular fluid; a substance produced by the body in response to low oxygen levels. This suggests that DHEA increases the supply of oxygen to the developing follicle and thus increases its quality, as it had been previously shown that oxygen plays a very important role in follicle development. Although the study demonstrated with statistical significance that supplementation with DHEA led to higher levels of HIF1, it could not be shown that supplementation led to better IVF outcomes, however this was attributed to the small sample size. The study concluded that DHEA supplementation is a viable option to increasing follicle development in women with POR as it is relatively cheap, easily administered and has minimal side effects.

==Lab 2 Assessment==

[[File:Macaque Oocyte.jpg|200px|thumb|left|A recently fertilised macaque oocyte.<ref><pubmed>20591337</pubmed></ref>]]

'''1. Upload an image from a journal source relating to fertilization or the first 2 weeks of development as demonstrated in the practical class. Including in the image “Summary” window: An image name as a section heading, Any further description of what the image shows, A subsection labeled “Reference” and under this the original image source, appropriate reference and all copyright information and finally a template indicating that this is a student image. {{Template:Student Image}}'''

The image to the left is from a journal article that investigated both in vivo and in vitro fertilisation in the macaque monkey. It shows a macaque oocyte containing both the maternal and paternal pronuclei. The link to this article can be found both below in 'references' and also in the description of the image.

'''2. Identify a protein associated with the implantation process, including a brief description of the protein's role.
'''

A protein associated with the implantation process is the glycoprotein ''fibronectin.'' It is involved in cell adhesion, growth, migration and differentiation; making it important in many bodily processes including wound healing and embryo implantation. In implantation, it guides cell attachment and migration, and the absence of fibronectin leads to defects in mesodermal, neural tube and vascular development; causing early embryo death.<ref>http://en.wikipedia.org/wiki/Fibronectin</ref>

==Lab 3 Assessment==

'''1. Identify the difference between "gestational age" and "post-fertilisation age" and explain why clinically "gestational age" is used in describing human development.'''

Gestational age is the time that has elapsed since the pregnant woman's last menstrual period began, measured in weeks. Post-fertilisation age is the time that has elapsed since the oocyte was fertilised by the sperm, also measured in weeks. Fertilisation reliably occurs 2 weeks after the last menstrual period, so gestational age is roughly 2 weeks greater than the post-fertilisation age. Gestational age is used clinically to describe human development as it is often difficult to identify the precise timing of fertilisation, thus the time since the last menstrual period (gestational age) is more convenient. Using gestational age, a pregnancy can be identified as premature or postmature. This identification has implications for a successful birth, as premature babies have a greater risk of complications and death.<ref>http://en.wikipedia.org/wiki/Gestational_age</ref>

'''2. Identify using histological descriptions at least 3 different types of tissues formed from somites.'''

Three different types of tissues formed from somites include the dermis (from dermatomes), skeletal muscle (from myotomes) and bone (from sclerotomes). Histologically, the dermis is an area of connective tissue under the outer, keratinised epidermis, that contains blood vessels and nerve endings. Skeletal muscle is muscle that appears striated and is under voluntary control by the nervous system. Bone is a specialised form of connective tissue that is organised into compact and spongy forms. The compact components provide rigidity while spongy bone works to distribute loads across the bone.<ref>http://en.wikipedia.org/wiki/Somite</ref>

==Lab 4 Assessment==

'''1. Identify the 2 invasive prenatal diagnostic techniques related to the placenta and 2 abnormalities that can be identified with these techniques.'''

An invasive prenatal diagnostic technique related to the placenta is an amniocentesis. This involves inserting a needle through the mother's abdomen and collecting a sample of the amniotic fluid, which contains cells shed by the fetus. Through analysis, this technique can identify chromosomal disorders such as Down syndrome as well as open neural tube defects such as spina bifida.<ref>http://www.knowyourgenes.org/prenatal_testing.shtml</ref>

Another invasive prenatal diagnostic technique is chorionic villus sampling (CVS). This involves inserting a catheter through the cervix and removing a small sample of placental tissue, which has the same genetic material as the fetus. This can then be tested for chromosomal abnormalities like Down syndrome, however cannot detect neural tube defects such as spina bifida, which an amniocentesis can detect.<ref>http://www.hopkinsmedicine.org/healthlibrary/conditions/a/pregnancy_and_childbirth/common_tests_during_pregnancy_85,P01241/</ref>

'''2. Identify a paper that uses cord stem cells therapeutically and write a brief (2-3 paragraph) description of the paper's findings.'''

A paper that uses umbilical cord stem cells therapeutically is one from a group of researchers at Seoul National University in South Korea entitled ''Comparison of Mesenchymal Stem Cells Derived from Fat, Bone Marrow, Wharton's Jelly, and Umbilical Cord Blood for Treating Spinal Cord Injuries in Dogs.''<ref><pubmed>22878503</pubmed></ref> They induced spinal cord injuries in dogs through the use of balloon catheter compression and then applied stem cells from a variety of sources to the site of injury and compared the recovery that was achieved between the different groups.

It was found that all stem cell treatments produced significant improvements in locomotion at 8 weeks after implantation, and that this was accompanied by increased numbers of neurons and neurofilament-positive fibers at the lesion site. However it was also found that even though the umbilical cord stem cells produced no greater improvement in locomotion than the other stem cells, the umbilical cord stem cells produced more nerve regeneration and anti-inflammation activity.

==Lab 5 Assessment==

'''Completing the in class Quiz!'''

==Lab 6 Assessment==

'''To Be added.'''

==Lab 7 Assessment==

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

A muscle satellite cell is a mononuclear progenitor cell containing very little cytoplasm found between muscle fibres.

Two examples of when satellite cells are activated occur during normal muscle growth and when the muscle is damaged. In both cases, under mechanical strain the satellite cells are activated and either form new muscle fibres or fuse to existing muscle fibres to make them larger.<ref>http://en.wikipedia.org/wiki/Myosatellite_cell</ref>

==Lab 8 Assessment==

'''Individual assessment this week relates to your group project.'''

'''1. Each student should now look at each of the other Group projects in the class.'''

'''2. Next prepare a critical assessment (should include both positive and negative issues) of each project using the project assessment criteria.'''

'''3. This assessment should be pasted without signature on the top of the specific project's discussion page (minimum length 3-5 paragraphs/project).'''

'''4. This critical assessment should also be pasted on your own student page. Each student should therefore have 5 separate reports pasted on their own page for this assessment item. Length, quality and accuracy of your reports will be part of the overall mark for this assessment (there will be a greater loading on this than simple question assessments).'''

'''Somatosensory'''

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.

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'''Taste'''

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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'''Olfaction'''

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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'''Abnormal Vision'''

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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'''Hearing'''

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.

==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.'''

A recent research paper on the development of the pancreas is one from 2000 (getting a bit old now, I suppose) entitled ''Regulation of pancreas development by hedgehog signaling.''<ref><pubmed>11044404</pubmed></ref> In this paper, the researchers investigated the effect that the genes Sonic hedgehog, Indian hedgehog and Patched 1 have on development of the pancreas by observing the effect that mutations in these genes have on the organism. They found that Sonic hedgehog represses the growth of the pancreas and is important in limiting its size. For example, if the tissues surrounding the pancreas are not expressing Sonic hedgehog, then the pancreas will grow uncontrollably up to three times its usual mass with much more pancreatic islets than usual, thus impairing the normal functioning of the tissues around it including the stomach and duodenum. They also found that Indian hedgehog plays a different role than Sonic, in that it is required for normal growth rather than repressing growth. In organisms where Sonic was absent along with Indian, there was no observed abnormally large growth, as seen when Sonic was absent but Indian was present. Finally, it was also concluded that without Patched 1, the pancreas is unable to maintain glucose homeostasis.

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

The developing teeth are composed of neural crest-derived mesenchyme and ectoderm from the first pharyngeal arch. Inductive processes occur between these two embryonic tissue types at week 6 to produce the first sign of teeth (teeth buds) in a process known as odontogenesis.<ref>http://embryology.med.unsw.edu.au/embryology/index.php?title=ANAT2341_Lab_9</ref>

==References==

<references/>

2012 Group Project 1

2012-10-02T00:49:18Z

Z3373894: /* Brief Timeline on Historical Developments on the Eye and its Embryology */

2012 Group Project 1

2012-10-02T00:47:16Z

Z3373894: /* Glossary */

2012 Group Project 1

2012-10-02T00:46:26Z

Z3373894: /* Glossary */

2012 Group Project 1

2012-10-02T00:18:48Z

Z3373894:

2012 Group Project 1

2012-10-02T00:10:37Z

Z3373894:

2012 Group Project 1

2012-10-02T00:09:18Z

Z3373894:

2012 Group Project 1

2012-10-02T00:06:03Z

Z3373894: /* Retina */

2012 Group Project 1

2012-10-02T00:04:27Z

Z3373894: /* Retina */

2012 Group Project 1

2012-10-01T23:55:43Z

Z3373894: /* Retina */

2012 Group Project 1

2012-10-01T23:43:15Z

Z3373894: /* Introduction */

2012 Group Project 1

2012-10-01T23:42:02Z

Z3373894: /* Introduction */

2012 Group Project 1

2012-10-01T23:21:39Z

Z3373894: /* Lacrimal Glands */

2012 Group Project 1

2012-10-01T23:18:38Z

Z3373894: /* Cornea */

2012 Group Project 1

2012-10-01T23:14:37Z

Z3373894: /* Iris */

2012 Group Project 1

2012-10-01T23:13:26Z

Z3373894: /* Ciliary Body */

2012 Group Project 1

2012-10-01T23:10:17Z

Z3373894: /* Retina */

2012 Group Project 1

2012-10-01T23:08:34Z

Z3373894: /* Retina */

2012 Group Project 1

2012-10-01T23:05:46Z

Z3373894: /* Retina */

2012 Group Project 1

2012-10-01T23:04:32Z

Z3373894: /* Retina */