Embryology - User contributions [en-gb]

2017 Group Project 4

2017-10-26T01:27:43Z

Z3416557:

{{ANAT2341Project2017header}}

=Eye Development=

==Introduction==

The eye is a complex sensory structure which allows a variety of species to intake and process visual information from the world around us. Most structures forming the human eye are developed between the embryonic weeks 3 through 10, deriving primarily from ectoderm, neural crest cells and mesenchyme.

This project page will start with a description of the functional anatomy of the adult eye, continue with a description and timeline of the embryonic formation and signaling pathways of important structures of the human eye and animal models and finish with an examination of congenital abnormalities, current research and pending questions for the near future.

We hope that this page provides you with an enjoyable, comprehensive introduction to the embryology of the eye (we have aimed to keep it a concise 'reachable' page!)

==Anatomy of the Adult Eye==

To discuss the key anatomical components of the eye, we will break down the eye in parts<ref>Chen, J., 2011. Handbook of Visual Display Technology. Springer Berlin Heidelberg. Chapter 2.1</ref>:

'''Supporting Structures (Orbit, Extraoccular Muscles, Lacrimal Gland, Eyelid)'''
[[File:22292144 10208413540209536 722417340 o.jpg|250px|thumb|right| '''Figure 1.''' Layers of the Eyeball]]
The orbit consists of a framework of bones and connective tissue which provide structural support and protection to the sensitive human eye. 7 bones contribute to the orbit of the eye: frontal, lacrimal, sphenoid, zygomatic, ethmoid, maxillary, palatine. Several openings exist in the orbital structure, 2 key fissures are the superior orbital fissure and inferior orbital fissure and the posterior optic canal. These openings allow cranial nerves passageway.

A set of 6 extra-ocular muscles allow for a strong voluntary control of the movement of the eye. These muscles include the superior rectus, inferior rectus, lateral rectus, medial rectus, inferior oblique, superior oblique muscles. These muscles are some of the smallest in the human body and are able to produce fast, controlled motion to focus on an object of interest.

The eyelid is the anterior covering of the eye, consisting of a thin fold of skin. It is controlled by the levitator palpebrae superioris muscle. Supero-lateral to the eyelid is the lacrimal gland, which secretes a film of tear, an important component to keeping the anterior surface of the eye moist. The eyelid assists in this process by opening and closing, or blinking, which spreads the tear film across the surface of the eye. Debris caught in the tear film is excreted through the lacrimal duct which is located on the infero-medial surface of the eyelid.
[[File:22251179_10208414266827701_870733039_o.jpg|250px|thumb|right| '''Figure 2.''' Anterior Part of the Eye]]

'''Layers of the Eyeball (Sclera, Choroid, Retina)'''

The superficial layer of the eyeball is the sclera, a thick fibrous layer which thickens as it extends posteriorly. The sclera is visible as the white part of our eye. Its function is to provide structural stability to the eye and serves as attachment site for extra-ocular muscle insertions. Deep to the sclera is the choroid, a vascular network which provides nourishment to the layers of the eyeball and plays a large role in the growth of the eye. Deep to the choroid is the retina, a network of nerve fibres which transmit visual information. The retina contains 2 types of photoreceptors which convert visible light into nerve impulses (rods and cones). Rods work best in low light environments while cones work best in high light enthronements and detect colour and sharp detail.<ref>Curcio CA, Hendrickson AE. Organization and development of the primate photoreceptor mosaic. Prog Ret Ret. 1991;10:89–120.</ref>: The retina does not extend to the anterior part of the eyeball, unlike the sclera and choroid layers.

'''Anterior structure (Lens, Cornea, Pupil, Iris, Ciliary Body, Conjunctiva, Anterior Chamber)'''

The most anterior component of the eyeball is the cornea, which is a multilayered avascular transparent structure. Its major function is to refract incoming light to assist image formation on the retina (contributes about 75% of total refraction). Continuous with the cornea superiorly and inferiorly is the conjunctiva. Deep to the cornea is the iris, the pigmented ring of the eye. The iris consists of 2 muscles which act to enhance and diminish the size of the pupil (the aperture surrounded by the iris) allowing light to enter the eye. Deep to the pupil and iris is the lens, which is a transparent structure which contributes the other 25% of the eye's refractive power. The lens changes shape through accommodation (focusing) controlled by the ciliary body muscles, changing the position of images to form them on the retina. The ciliary body is the anterior extension of the choroid. Between the anterior surface of the lens and posterior surface of the cornea lies the anterior chamber. This chamber is filled with aqueous humour supplied by the ciliary body, which provides nutrients to ocular structures and maintains intra-ocular pressure.
[[File:22251314_10208414283908128_862494115_o.jpg|250px|thumb|right| '''Figure 3.''' Posterior Part of the Eye]]

'''Posterior structure (Optic Nerve, Optic Disc, Macula, Fovea, Posterior Chamber)'''

In the posterior section of the retina is the macula, a central spot in which a high concentration of cone photoreceptors are found. The direct centre of the macula is called the fovea which contains solely cone photoreceptors. The fovea is the only part of the eye which can conduct 'perfect' 20/20 vision. It has a high workload and hence a strong vascular supporting structure<ref><pubmed>6462623</pubmed></ref>:. The most posterior part of the eye is the optic nerve (along with the central retinal artery and central retinal vein), which is responsible for transporting nerve impulses to the cerebral cortex for processing. The opening of the optic nerve is called the optic disc, which contains no photoreceptors and is a blind spot of the eye. Between the posterior surface of the lens, the retina and the optic disc is the posterior chamber. The posterior chamber contains a vitreous humour, a jelly like substance with a high viscosity.

==Embryonic Contributions==

Eye development is a complex process. It involves the formation of the retina and the lens, which we together call the eyeball. It also involves the formation of auxiliary eye structures which are the eyelid, lacrimal gland, and cornea. The retina is formed from the neuroectoderm, the lens from the surface ectoderm and the auxiliary tissues are formed from the head surface ectoderm, neural crest cells and the head mesoderm <ref name="PMC3104407><pubmed>PMC3104407</pubmed></ref>.

[[File:Stage14 sem2cl.jpg|300px|thumb|right| '''Figure 4.''' Stage 14]]

{| class="wikitable"
! style="background:#f4a941" | Embryonic contributions
! style="background:#f4a941" | Eye component
|-
| Neuroectoderm of the forebrain || Retina, Posterior layers of the iris, The optic nerve
|-
| Surface ectoderm of the head || The lens of the eye, The corneal epithelium
|-
| Mesoderm between the neuroectoderm and the surface ectoderm || The fibrous and vascular coats of the eye
|-
| Neural crest cells || Choroid, Sclera, Corneal endothelium
|}

==Timeline of embryonic development==

{| class="wikitable"
! style="background:#f4a941" | WEEK
! style="background:#f4a941" | DEVELOPMENT
|-
| 3-4 || Eye fields, Optic vesicles
|-
| 5-6 || Optic Cup, Lens Vesicle, Choroid Fissure, Hyaloid Artery
|-
| 7-8 || Cornea, Anterior Chamber, Pupillary Membrane, Lens, Retina
|-
| 8-10 || Eyelids
|-
| 9-15 || Iris, Ciliary Body
|}

==Carnegie Stages==

Carnegie Stages are a system of 23 stages used to describe developmental events of the vertebrate embryo. At stage 10 we see early signs related to eye development. The table below is an made of knowledge from Anthony A. Person's article <ref><pubmed>7364662</pubmed></ref>.

{| class="pretty table"
|-bgcolor = "DDCEF2"
|'''Stage'''
|'''Events'''
|-bgcolor="FAF5FF"
|'''Stage 10 (22 days)'''
|The optic primordium has developed. Two small grooves develop on each side of the developing forebrain in the neural folds - this is the optic grooves. The optic placode has begun to develop, which is seen by a small thickening of the surface ectoderm lateral to the hindbrain.
|-
|'''Stage 11 (24 days)'''
|Optic vesicle begins to form from the optic groove.

[[File:Stage11 histology-optic pit.jpg|300px|'''Figure 1.''' Stage 11]]
|-bgcolor="FAF5FF"
|'''Stage 12 (26 days)'''
|The optic vesicles have extended from the forbrain to the surface ectoderm. The optic vesicle now lies close to the surface ectoderm.
|-
|'''Stage 13 (28 days)'''
| The optic vesicle interacts with the surface ectoderm and will induce this ectoderm to form the lens placode, which is the precursor of the lens. Optic evagination differentiation makes it possible to identiy optic parts of retina, future pigmented layer of retina and optic stalk.

[[File:Stage_13_image_060.jpg|300px|'''Figure 2.''' Stage 13]]
|-bgcolor="FAF5FF"
|'''Stage 14 (32 days)'''
| The lens placode is indented by the lens pit and is cup-shaped.
|-
| '''Stage 15 (33 days)'''
| The lens pit will close and form a circle that separates from the surface ectoderm and becomes the lens vesicle. The lens vesicle and optic cub lie close to the surface ectoderm, which creates a slight elevation in the region of the eye.
|-bgcolor="FAF5FF"
| '''Stage 16 (37 days )'''
| The lens body has grown and now has a D-shaped lens cavity. First indication of the development of the eyelids visible as eyelid grooves above and below the eye.
|-
| '''Stage 17 - 19'''
| Retinal pigment is visible and the retinal fissure is almost closed. The eyes are still laterally placed but starts to take a more anterior position. The lower eyelid fold develops first and then the eyelid fold above the eye.
|-bgcolor="FAF5FF"
| '''Stage 18 (44 days)'''
| Mesenchyme invades the region between the lens epithelium and the surface ectoderm. The eyes have shifted to a more anterior position. The groove above and below the eyes are deeper but have not joined yet.
|-
| '''Stage 19 - 22'''
| The eyelid folds develop into the eyelids and the upper and the lower eyelids now meet at the outer canthus, which is the corner of the eye.

[[File:Stage 22 image 208.jpg|300px|'''Figure 3.''' Stage 22]]
|-bgcolor="FAF5FF"
| '''Stage 20 (51 days)'''
| The lens cavity is lost. The upper and lower lids meet laterally and medially. The eyelids now partly cover the eye. Lens suture begins to form.
|-
| '''Stage 23 (57 days)'''
| End of embryonic period. The face begins to look human. Eyelids closure is complete.
|-
|-bgcolor="FAF5FF"
|-
|}

==Development of the eye components==

===Introduction===

<html5media width=“480" height="360">https://www.youtube.com/embed/ghHDFWlfpoQ</html5media>

[[File:DevelopmentEye-PMC43029243.jpg|400px|thumb|right|'''Figure 5.''' Stages of lens formation in mouse embryos]]

The eye starts to develop at 22 days. The optic grooves (sulci) appears in the neural folds at the cranial end of the embryo. When the neural fold fuse to form the forebrain, the optic grooves will form '''optic vesicles'''. The optic vesicles are continuous cavities from the cavity of the forebrain and project from the wall of the forebrain and into the mesenchyme. The optic vesicle extends from the diencephalon and will come in contact with the surface ectoderm of the head. This induces the formation of a lens placode <ref name="Larsen'sHumanEmbryology">Schoenwolf, G.C., Bleyl, S.B., Brauer, P.R., Francis-West, P.H. & Philippa H. (2015). Larsen's human embryology (5th ed.). New York; Edinburgh: Churchill Livingstone.</ref>.

The surface ectoderm near the optic vesicles will thicken and form the '''lens placodes'''. The lens placodes will sink into the surface ectoderm and form '''lens pits'''. The edges of the lens pits will travel towards each other and fuse to form round '''lens vesicles''', which will later lose connection with the surface ectoderm. The optic vesicles do also keep developing - they will form double-walled '''optic cups''' which are connected to the brain by the '''optic stalk'''. The two layers of the optic cup will differentiate in different directions. The cells of the outer layer will produce melanin pigment and later become the '''pigmented retina'''. The cells of the inner layer of the optic cup will proliferate fast and develop glia, ganglion cells, interneurons and light-sensitive photoreceptor neurons. These cells are in the '''neural retina'''. The ganglion cells of the retina are neurons that send signals to the brain. The axons of the ganglion cells of the neural retina will grow in the wall of the optic stalk. The cavity in the optic nerve will start disappearing, and instead, the axons of the ganglion cells will form the '''optic nerve'''. The optic stalk is now the optic nerve <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>

The optic cups will fold inwards around the lens while the lens vesicles have grown inwards so they have fully lost their connection with the surface ectoderm, which locates them in the cavities of the optic cups. The retinal fissures (linear grooves) will develop and cover the ventral surface of the optic cups and down to the optic stalk. The retinal fissures contain vascular mesenchyme and hyaloid blood vessels will develop here. The hyaloid artery supplies the structures in the eye with blood and the hyaloid vein will return the blood from these structures <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

'''Formation of the optic vesicle'''

It is a specific area of the neural ectoderm that will become the optic vesicle - this happens because of a group of transcription factors - Six3, Pax6, and Rx1. These transcription factors are expressed in the most anterior tip of the neural plate. This area will split into bilateral regions and form the optic vesicles. The Pax6 protein has shown to be especially important for the development of the lens and retina. This protein is important for photoreceptive cells in all phyla. Pax 6 is also present in the murine forebrain, hindbrain, and nasal placodes, but the eyes are most sensitive its absence <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

The sonic hedgehog gene is important for the separation of the single eye field into two fields. If this gene is inhibited, the eye field will not split which will result in cyclopia, a single eye in the center of the face <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

===Retina===

[[File:Bailey463.jpg|400px|thumb|right|'''Figure 6.''' Diagram of developing lens and optic cup]]

The retina is the essential component of the eye with the primary function of photoreception <ref><pubmed>7084144</pubmed></ref>. Formation of the retina begins with the specification of retinal cells in the anterior neuroectoderm. First morphological sign of eye development is the formation of two lateral grooves in the anterior neuroectoderm, which is called the optic sulci. The cells of the optic sulci will evaginate and form the optic vesicle. The distal portion of the optic vesicle will form the retina and the proximal will form the optic stalk <ref><pubmed>18675797 </pubmed></ref>. The retina develops from the walls of the optic cup, these walls develop into the two layers of the retina. The thin, outer layer of the optic cup will become the pigment layer of the retina and the thick, inner layer of the optic cup will differentiate into the neural retina. Forkhead transcription factors are regulating the proliferation and differentiation of the retinal precursor cells. During the embryonic and early fetal periods, the two layers of the retina are separated which makes an intraretinal space. The intraretinal space is derived from the cavity of the optic cup. The two layers of the retina will fuse and the intraretinal space will gradually disappear <ref name="Larsen'sHumanEmbryology">Schoenwolf, G.C., Bleyl, S.B., Brauer, P.R., Francis-West, P.H. & Philippa H. (2015). Larsen's human embryology (5th ed.). New York; Edinburgh: Churchill Livingstone.</ref>.

When the lens is developing the inner layer of the optic cup starts to proliferate and forms a thick neuroepithelium which will later differentiate into the neural retina. The neural retina contains photoreceptors and the cell bodies of neurons and is the light-sensitive region of the retina. The axons of the ganglion cells in the neural retina grow in the wall of the optic stalk and will form the optic nerve <ref name="Larsen'sHumanEmbryology">Schoenwolf, G.C., Bleyl, S.B., Brauer, P.R., Francis-West, P.H. & Philippa H. (2015). Larsen's human embryology (5th ed.). New York; Edinburgh: Churchill Livingstone.</ref>.

===Lens===

Human lens induction occurs at around 28 days and is completed around day 56. The surface ectoderm will thicken near the optic vesicle and create the lens placode and later form the lens vesicle <ref><pubmed>20171212 </pubmed></ref>. Lens cells come from ectoderm and differentiate into either lens fibers or the lens epithelium. The anterior monolayer of epithelial cells of the lens will create the lens epithelium, which makes the sheet of cuboidal epithelium covering the anterior surface of the lens. The posterior lens vesicle cells will produce the linear primary fibre cells aligned parallel to the optic axis. These fibres will create the lens mass and form the embryonic lens nucleus. The lens epithelial cells will keep proliferating and produce new cells which generate a secondary lens fiber cells. This rows of cell will form the outer shells and keep the lens growing throughout life. This makes the eye lens unique - it will have an addition of new cells inside the surrounding capsule all the time <ref><pubmed>25406393</pubmed></ref>.

===Ciliary Body===

The ciliary body is a muscular and secretory tissue and is located directly behind the lens. The ciliary body forms part of the anterior segment of the eye and is an important regulator of eye physiology and the vision. The ciliary body produces the aqueous fluid which fills the eyes and nourishes the lens and cornea - this aqueous fluid function to keep the eye in a pressurized and inflated state, which is important the vision.The ciliary body also synthesizes collagenIX and tenasin-C <ref><pubmed>17275804</pubmed></ref>.

The ciliary body extends from the iris root (anteriorly) to the ora serrata (posteriorly). It consist of ciliary muscles and ciliary processes. Each ciliary process (fold) is covered by a double-layered secretory epithelium; the outer pigmented and the inner unpigmented (closes to the lens). The epithelial layers of the ciliary body comes from the retina of the optic cup. We see two different ciliary body epithelium: the inner non-pigmented ciliary epithelium which is connected with the neural retina and the outer pigmented ciliary epithelium which is connected with the retinal pigmented epithelium. The epithelium of the iris is the further anterior extension. The epithelial layers are associated with a stroma containing the ciliary muscle. The ciliary muscle is complex, but can be divided into three portions; anterior, posterior and internal <ref><pubmed>12127103</pubmed></ref>.

In the chick eye development, we see the mesenchyme grow together on the margin of the optic cup and will form the stroma of the ciliary body and the iris, which is located more anteriorly. It is unknown how if the lens has a role in inducing the secretory ciliary body epithelium and the muscular iris epithelium <ref><pubmed>17275804</pubmed></ref>.

===Iris===

The iris is the circular, pigmented muscular portion of the eye with a central aperture that is the pupil. The main function of this round muscle is to manipulate pupil diameter as an adjustment to various conditions and to control the amount of light entering the eye <ref name=’’21413392’’><pubmed>21413392</pubmed></ref>. This is influenced by dilator pupillae (radial) and sphincter pupillae (constricting) muscles. Iris pigmentation is dependent on the abundance and distribution of certain types of melanin in the posterior epithelium of the iris (eumelanin and pheomelanin) <ref name=’’21413392’’/>.

The Iris develops at the end of the third month of development. The iris is a thin layer and derives from the anterior rim of the optic cup <ref><pubmed>22219630</pubmed></ref>. The iris is formed by the pigment-containing internal and external layers of the optic cup and by a layer of vascularised connective tissue which also contains the pupillary muscles. Internal layers of the optic cup form the non-pigmented iris parts whereas the external layers of the optic cup develop into the pigmented epithelial structures. <ref name=’’18168498’’><pubmed>18168498</pubmed></ref>. Iris stroma develops as a result of neural crest cell migration – within this stroma, the dilator and constrictor muscles develop from the neuroectoderm of the optic cup. In the anterior of the eye, the optic epithelium is non-neural and matures as ciliary body and iris epithelia <ref name=’’18168498’’/>.

===Cornea===

The cornea is the unique, transparent and avascular component located at the most anterior section of the eye. It is composed of five layers stemming from the 3 main layers of epithelium, stroma and endothelium:

* Corneal epithelium (most anteriorly) – consisting of multiple layers of cells which rest on a basement membrane.
* Bowman’s membrane – a clear, acellular homogenous layer. This layer is a modified portion of the stroma and has no regenerative capacity as a response to damage <ref name=''7084144''><pubmed>7084144</pubmed></ref>.
* Corneal stroma – largest portion of the retina consisting of collagenous tissue.
* Descemet’s membrane – a homogenous, elastic true basement layer with a regenerative capacity.
* Corneal endothelium – a single layer of cuboidal cells responsible for the maintenance of the dehydrative nature of corneal tissue. <ref name=''7084144''/>.

Corneal development involves interactions between ectoderm-derived tissues. More specifically, the corneal epithelium arises from interactions between the cranial ectoderm and optic vesicles derived from the neural ectoderm <ref name=''26310148''><pubmed>26310148</ref></pubmed>. The neural tube and the adjacent ectoderm give rise to the neural crest cells which are multipotent with a migratory capacity. These cells contribute to the formation of corneal epithelium and the stromal cells. Innervation of the cornea stroma and epithelium is derived from both the neural crest and the ectodermal placode <ref name=''26310148''/>. The endothelium is comprised of differentiated neural crest cells which contribute to the later formation of Descemet’s membrane <ref><pubmed>6511224</pubmed></ref>.

===Aqueous Chambers===

There are two aqueous chambers of the eye: anterior and poster. These chambers are filled with a plasma-like fluid called aqueous humour and is produced by the ciliary body and trabecular meshwork in 3 main stages: diffusion, ultrafiltration and active secretion <ref><pubmed>6763801</pubmed></ref>. The main function of this fluid is to maintain the intraocular pressure as well as provide structural integrity to the round shape of the eyeball. This structure also has a role in the immune response and provides nutrition to the avascular tissue (e.g., the cornea and lens). <ref><pubmed>21293732</pubmed></ref>.

The anterior chamber is defined as the developed space posterior to the cornea (between the cornea and the iris) and develops at the stage of differentiation of the mesodermal portion of the iris <ref name=’’18168498’’/>. The space defining the posterior chamber develops as the mesenchyme between the lens and the peripheral iris.

===Choroid and Sclera===

The choroid and sclera are both surround the eye and are located adjacent to each other (the choroid lines the inner portion of the sclera). The sclera is the outer, fibrous white layer of the eye which functions as a supportive wall of the eye ball and is continuous with the cornea <ref name=''7084144''/> . The heavy vasculature of the choroid provides a major supply of oxygen and nourishment to the retina <ref><pubmed>20044062</pubmed></ref>.
They are derived from interactions between the neural crest and mesoderm-derived mesenchyme. The sclera forms as a result of condensation of the mesenchyme outside the optic cup <ref><pubmed>1628748</pubmed></ref>.
The choroid arises from the mesenchyme surrounding the optic vesicle and the cranial neural crest cells. The first vasculature structures appear in the choroid during week 15 in the form of arterioles and venules; veins and arteries become distinguishable by week 22 <ref name=’’2199235’’><pubmed>2199235</pubmed></ref>.

===Extraocular muscles===

The extraocular muscles are responsible for eye movement within the eye orbit – a critical aspect of sight and communication. 6 main muscles contribute to eye movement. These include: superior rectus, inferior rectus, lateral rectus, medial rectus, superior oblique and inferior oblique.

The development of these muscles is dependent on interactions between the eye, its muscles and the neural crest. <ref name=''21482859''><pubmed>21482859</pubmed></ref>.
Somites supplied by cranial nerve III forms 5 of the 6 extraocular muscles which form an interlocking tendinous ring made of fibrous connective tissue. The 5 muscles include the lateral, medial, superior and inferior rectus, and the superior oblique muscle. This common tendinous ring is known as the annulus of Zinn and surrounds the entry of the optic nerve. The remaining sixth muscle is the inferior oblique muscle and is separate from the aforementioned tendinous ring due to its distinct point of origin. <ref name=''21482859''/>.

===Eyelids===

The eyelids are upper and lower folds of skin functioning as a barrier protecting the anterior surface of the eye from direct local injury. Eyelids also regulate light exposure, distribute precorneal tear film over the corneal surface when blinking and are involved in functions involving tear flow <ref><pubmed>1993591</pubmed></ref>.
No sign of eyelid fold development is evident at week 5 however at this stage the lens pit begins to invaginate from the surface ectoderm <ref name=’’27124372’’><pubmed>27124372</pubmed></ref>. Week 6 initiates the timeline of eyelid development as small depressions emerge in the surface ectoderm both above and below the developing eye – these rapidly deepen to form the folds of the eyelids <ref name=‘’7364662’’><pubmed>7364662</pubmed></ref>. The lower eyelid fold develops first and, by the end of week 6, the lower fold is more distinct than the upper eyelid fold <ref><pubmed>21416630</pubmed></ref>. Week 7 marks the point at which both the upper and lower folds are distinctly developed and during this stage, the upper lid assumes its more dominant role <ref name=’’27124372’’/>. The eyelid is not fully closed - there is a gap between the folds and the cornea is slightly visible – they eventually undergo fusion in week 8 <ref name=’’27124372’’/>.

===Lacrimal Glands===

The lacrimal glands are exocrine glands located in the upper lateral region of each eye orbit which secrete the aqueous potion of the tear film. This film is continuously secreted and functions to clean and protect the external surface of the eye, keeping the environment constantly moist and preventing possible injury from dust and other particles <ref><pubmed>17001201</ref>.
Lacrimal gland morphogenesis is identified in three stages.

* The first is the presumptive glandular stage. This stage involves the thickening of the conjunctival superior fornix epithelium and the condensing of the surrounding mesenchyme <ref name=’’14635806’’><pubmed>14635806</pubmed></ref>.

* The second is the bud stage. This stage is considered the initial sign of glandular formation due to the development of nodular structures and lumina within epithelia buds <ref name=’’14635806’’/>.

* The third is the glandular maturity stage (week 9-16). In this stage, the lacrimal gland begins to morphologically mirror the adult gland <ref name=’’14635806’’/>.

==Signalling pathways and transcription factors involved throughout eye development==

===Eye field development===

Many signalling pathways and transcription factors are involved in the development of the eye field (which forms in addition to the telencephalon and diencephalon as part of division of the anterior neural plate). Eye progenitor cells are guided into the eye field region by fibroblast growth factor, bone morphogenetic protein and Wnt-signalling pathways <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>. Additionally, interactions between canonical and non-canonical Wnt-signalling have been shown to maintain the eye field border <ref name=’’16413771’><pubmed>16413771</pubmed></ref>.

The cells of the eye field express eye field transcription factors, some of which include Rx1/Rax, Pax6, Lhx2, Six3 and Otx2. Six3, Pax6, Otx2 and Rx1 specify retinal lineage and regulate progenitor cell movement to guide them to their correct locations <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>. Six3 also partly mediates Wnt-signalling repression, allowing for the development of the optic vesicles from the eye field <ref name=’’23684892 ’’><pubmed>23684892 </pubmed></ref>. Lhx2 maintains optic lineage in eye progenitor cells and suppresses the potential for differentiation towards different fates <ref name=’’23595746’’><pubmed>23595746</pubmed></ref>.

===Eye field division and progression to optic cup===

TGF-β, FGF and Shh family factors secreted by the axial mesoderm underlying the eye field initiate its splitting into two bilateral, symmetric eye primordia <ref name=’’23684892 ’’><pubmed>23684892 </pubmed></ref>. These factors also regulate the expression of transcription factors Pax2, Pax6, Vax1 and Vax2, thereby establishing the boundaries and patterning the proxiodistal and ventronasal axes of the optic vesicles <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>.

Despite the close relationship between cellular proliferation and morphogenesis, optic vesicle evagination does not appear to be mainly driven by proliferation <ref name=’’23684892 ’’><pubmed>23684892 </pubmed></ref>. Alternatively, it has been shown that retinoic acid has critical importance in optic vesicle evagination to form the optic cup <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>. Rx3 activity has also been observed to have involvement in optic vesicle evagination <ref name=’’23684892 ’’><pubmed>23684892 </pubmed></ref>.

===From optic cup to developed eye===

Lens placode maturation and lens development is dependent on Pax6 expression and regulation. During placode formation bone morphogenetic protein and fibroblast growth factor signalling regulate Pax6. Within the presumptive lens ectoderm, Pax6 is regulated by Six3 and Meis. However, within the presumptive epithelium Pax6 is a regulating factor, regulating the expression of Sox2 and eventually Six3 once the lens placode is formed <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>.

Meanwhile, in the primordial retina retinal progenitor cells become retinal ganglion cells through the expression of the basic helix-loop-helix transcription factor ath5 (which is regulated by Hh and Fgf signalling. The amacrine, horizontal and bipolar cells of the retina are generated by a variety of transcription factors, some of which include Pax6, Six3 and Foxn4 <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>. Crx and Otx2 positive cells progress towards photoreceptor fates and are further developed into rods and cones based on specific transcription factor expression (TRβ2 and RxRγ expression is required for cones, where as Nrl, Nr2e3 and Ascl1 expression is required for rods) <ref name=’’20648062’’><pubmed>20648062</pubmed></ref>. The transcription factors required for the development of the retinal pigment epithelium include Mitf, Otx1/Otx2 and Pax6. TGF-β, FGF, BMP and Hh signalling from the surrounding mesenchyme have also been shown to help induce retinal pigment epithelium fate in progenitor cells <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>.

Within the choroid, the expression and regulation of many different factors and signalling pathways is required for the development of proper arterial-venous connections, allowing for the functional circulation of nutrients and oxygen throughout the eye. VEGF, bFGF, PDGF and PEDF (from the retinal pigment epithelium) drive the development and maturation of choroidal blood vessels. Vascular patterning is regulated by the interactions between VEGF and Delta-like 4 factors. Additionally, Notch signalling has been shown to have importance in the formation of capillary beds <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>.

===Eye formation in the absence of the retina===

The gene Rx is a key component in the formation of retinal structures. Studies have shown that mice lacking Rx function do not form optic sulci or optic vesicles and do not have retina-specific gene expression. There has been made studies in human, medaka, zebrafish and Xenopus which suggest that Rx genes are required for the formation of the vertebrate retina. It is also shown that in Rx-deficient mouse embryos the mature lens does not develop. This indicates that retinal cells are necessary for lens formation, and if the mouse is lacking Rx gene, then it will not display any retina-specific gene expression <ref name="PMC3104407"/>.

It is thought that signaling from the optic vesicle is important to activate the lens-specific gene and the formation of the lens placode. If there are no retinal cells generated, then the morphogenesis of the optic cup does not take place and the lens will not form. The study also showed that elimination of β-catenin expression in the head surface ectoderm in Rx-deficient embryos would develop a lens-like structure even though there were no optic vesicle/cup. Elimination of β-catenin lead to upregulation of Pax6, which is a gene that has a key role in lens formation. This indicates that the optic vesicle/cup might not be required for lens formation. The lens developed smaller than in wild type embryos, which means that the optic cup/vesicle might have an effect on a determination of the size of the lens. It could be that the developing optic vesicle/cup shields the developing lens placode from signals for other tissues that could disturb the lens formation <ref name="PMC3104407"/>.

It is not fully understood if the formation of the auxiliary eye structures is dependent on the development of the eyeball and its components, the retina and the lens. A study made my Eric C. Swindell and al. showed that auxiliary eye structures form even in the absence of retinal morphogenesis and retina-specific gene expression. This indicates that there are two separate developmental processes involved in the formation of the eye and its associated structures. In the absence of the retina and the lens, we still see specific gene expression in the surface ectoderm initiating the formation of auxiliary eye structures like eyelids and lacrimal glands <ref name="PMC3104407"/>.

==Current research==

===Iris epithelium cells as a potential source for regenerative medicine for retinal pigment epithelium degeneration===

The retinal pigment epithelium (RPE) is a monolayer of neural-crest-derived cells and is located between the photoreceptors and the choroid. There are many disorders that involve dysfunctional RPE and leads to retinal degenerative diseases. There is no treatment for these diseases, therefore, one of the most promising future therapy for RPE related disorders is to replace the cells of the dysfunctional RPE <ref name="PMC5565104><pubmed>PMC5565104</pubmed></ref>..

Studies have focused on the development and use of induced pluripotent stem cells (iPSC) for cell replacement therapy. It is possible to differentiate iPSC in vitro towards RPE cells and use them for experimental transplantation studies in animal models. But an alternative strategy for a retinal replacement is based on transdifferentiation (direct conversion) and involves transforming an adult somatic cell into another adult somatic cell. Use of overexpression of cell-lineage specific genes can convert one cell into another cell type and skip the pluripotent state. Iris epithelium (IE) cells might be able to be transdifferentiated into the RPE since both RPE and IE are neuro-epithelia and has a common embryological origin - they both derive from neuroectoderm of the developing optic cup <ref name="PMC5565104"/>.

A study made by Anna Bennis et al. <ref name="PMC5565104"/>. has shown that the canonical pathways for the most highly expressed genes of the IE and the RPE were very similar. Wnt signaling pathways has shown to be active in the IE but not in the RPE. The Wnt signaling pathway consists of a group of signal transduction pathways that has an influence on cell fate determination and cell proliferation during embryonic development. Activation of Wnt SP makes it possible to reprogram somatic cells (also retinal neurons) into iPSC and is important for the differentiation of pluripotent stem cells to RPE cells. The high expression of Wnt SP genes in the iE suggests that the IE has a multipotent character during life and therefore could be transformed into RPE cells used for RPE replacement <ref name="PMC5565104"/>.

===Developing Retinal Ganglion Cells from Pluripotent Cells===

A 2016 paper <ref>Ohlemacher, S. K., Sridhar, A., Xiao, Y., Hochstetler, A. E., Sarfarazi, M., Cummins, T. R. and Meyer, J. S. (2016), Stepwise Differentiation of Retinal Ganglion Cells from Human Pluripotent Stem Cells Enables Analysis of Glaucomatous Neurodegeneration. Stem Cells, 34: 1553–1562. doi:10.1002/stem.2356</ref> addressed the difficulty of culturing retinal ganglion cells (RGC) from pluripotent cells (both embryonic and enducded) due to a lack of known specific markers to communicate the cell to develop into a RGC. This study found a method of developing RGC through a stepwise approach involving retinal progentior cells. The RGC cells created showed no functional difference that normal RGC cells. Applications of this discovery have included helping to treat patients with congenital glaucoma abnormalities

===UNSW Optometry and Vision Science Current Projects===

Additionally, UNSW has a number of current research projects currently being undertaken <ref>https://www.optometry.unsw.edu.au/research/current-research</ref>

A few interesting topics include:

- Biochemical changes in the tear film in relationship to the corneal structural changes in diabetes so as to be able to predict nerve damage earlier

- The use of video games and virtual reality (visual electrophysiology) to help treat some congenital anomalies such as lazy eye

- How retinal circuitry operates with regards to neurotransmitter release, receptor location and receptor function, allowing the development of a retinal roadmap which can be applied to retinal diseases

==Animal Models==
The zebrafish species is used to investigate ocular development, function and disease due to having the same morphology as other vertebrates including humans. The advantages of zebrafish include: they are able to quickly reach their sexual maturity, they behaviour can be observed quite early on because of their rapid development and most importantly, their embryos are translucent. Zebrafish is also active during the day therefore their retina contains a large number of diverse cone subtypes in additions to rods. <ref name="Zebrafish"> Glass, A. S. & Dahm, R. (2003). The Zebrafish as a Model Organism for Eye Development. ''Opthalmic Research, 36''(1), 4-24. doi: 10.1159/000076105</ref>

[[File:Chokh.png|250px|thumb|left| '''Figure 11.''' Wild type zebrafish vs chokh/rx3 knockout. Morphological differences with the absence of eyes in the knockout.]]
Through studying zebrafish, it was found that that a mutation in ''chokh/rx3'' gene results in the absence of eyes during the earliest stages of development due to failure of the retinal progenitor cells. <ref name="chokh">Loosli, F., Staub, W., Finger-Baier, K. C., Ober, E. A., Verkade, H., Wittbrodt, J. & Baier, H. (2003). Loss of eyes in zebrafish caused by mutation of chokh/rx3. ''EMBO Reports, 4''(9), 894-899. doi: 10.1038/sj.embor.embor919 </ref>. Optical vesicle is turned inside out and the neuronal differentiation is blocked. In this study, they have found that the DNA-binding homeodomain and the the entire C-terminal portion led to a nonsense mutation that resulted to complete loss of function in the eye. It was concluded that the gene ''chokh/rx3'' is important for the developing optic primordia.

==Congenital Abnormalities==
Although quite rare, abnormalities can occur during the embryonic development that causes serious effects to the features of the eyes, its function as well as the further normal development after birth. These abnormalities can occur unilaterally or bilaterally and it is also common for most reported cases to have more than one type of eye abnormalities at a time. Thus, the estimated prevalence statistics listed in the table can overlap.

{| class="wikitable"
! style="background:#f4a941" | Congenital Anomalies
! style="background:#f4a941" | Description
! style="background:#f4a941" | Epidemiology
|-
| Anopthalmia || The absence of the eyes.
| rowspan="2" | Prevalence: Anophthalmia-Microphthalmia Syndrome was estimated to be 5.3 per 100 000 cases <ref name="Anophthalmia">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: [[http://www.orpha.net/consor/cgi-bin/index.php]] </ref>
Cause: SOX2 gene mutation <ref name="SOX2 Gene"> Mauri, L., Franzoni, A., Scarcello, M.,
Sala, S., Garavelli, L. Modugno, A., ... Penco, S. (2015). SOX2, OTX2 and PAX6 analysis in subjects with anophthalmia and microphthalmia. ''European Journal of Medical Genetics, 58'', 66-70. doi: 10.1016/j.ejmg.2014.12.005 </ref>
|-
| Microphtalmia || Abnormal reduction in size of the eyeballs.
|-
| Keratoglobus || Structural abnormalities in the formation of the cornea - unknown cause - fixable through surgery<ref name="PMID23807384"><pubmed>23807384</pubmed></ref>
| Prevalence: understood to be a rare condition<ref name="PMID23807384"><pubmed>23807384</pubmed></ref>
|-
| Ptosis ('Lazy Eye')|| Structural abnormalities in the eyelid, can be congenital - specifically the failure of innervation of the oculomotor nerve for levator palpebrae superioris <ref name="PMID8759493"><pubmed>8759493</pubmed></ref> - fixable through surgery
| Prevalence: a relatively well known abnormality
|-
| Aphakia || Te absense of a lens in the eye, causing a loss of accommodation and hence far-sightedness. People with aphakia have relatively small pupils which are unable to dilate as much <ref name="PMID28913511"><pubmed>28913511</pubmed></ref>
| Prevalence: a rare congenital abnormality
|-
| Coloboma || A condition where parts of the eye is missing and failed to develop normally.
| Prevalence: Occular coloboma was estimated to be 8.0 per 100 000 cases <ref name="Anophthalmia">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: [[http://www.orpha.net/consor/cgi-bin/index.php]] </ref>
|-
| Aniridia || Complete or partial absence of the iris.
| Prevalence: Estimated to be 1.5 per 100 000 cases <ref name="Anophthalmia">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: [[http://www.orpha.net/consor/cgi-bin/index.php]] </ref>
|-
| Optic Nerve Hypoplasia || A condition where the optic nerves are underdeveloped.
| Prevalence: Reported to be the most common abnormality <ref name="The Optic Nerve Hypoplasia">Ryabets-Lienhard, A., Stewart, C., Borchert, M., & Geffner, M. E. (2016). The Optic Nerve Hypoplasia Spectrum - Review of the Literature and Clinical Guidelines. ''Advances in Pediatrics, 63'', 127-146. doi: 10.1016/j.yapd.2016.04.009 </ref>
*10.9 per 100 000 in United Kingdom
*17.3 per 100 000 cases in Sweden.
*6.3% of cases was reported in New Zealand
|-
|}

<gallery>

Anophthalmia.jpeg|'''Figure 8.''' Anopthalmia
Microphthalmia-500px.jpg| '''Figure 9.''' Microphthalmia
Opac_figure_7.jpg| '''Figure 10.''' Iris Coloboma
Opac figure 10.jpg| '''Figure 11.''' Partial Aniridia
</gallery>

==Future questions==
===Will it be possible to have eye transplants in the future?===
Lots of research has been done in making a whole-eye transplantation successful in order to finally cure blindness. Blindness is a worldwide problem and is currently untreatable due to the fact that retinal ganglion cells and the optic nerves do not regenerate. This can result from diseases including macular degeneration and end of stage glaucoma. The first successful eye transplantation was led by Stone and Cole in 1943<ref name="Return of Vision"> Stone, L. S. & Cole, C. H. (1943). Grafted Eyes of Young and Old Adult Salamanders (Amblystoma Punctatum) Showing Return of Vision. ''Yale Journal of Biology and Medicine, 15''(5), 735-754.2. PMCID: PMC2601300</ref> investigating 104 samples of the salamander species, ''Amblystoma Punctatum'', and one of its eyes were either implanted back into the same animal or it was completely transplanted to a new host. It was reported that circulation in the iris was re-established, retina was able to regenerate, a new optic nerve was connected to the brain through the optic chiasma and ocular movements were regained. Vision was reestablished by the second month. In a more recent study, in 2015, Li et al.<ref name="Structural Integrity"> Li, Y., Komatsu, C., Wang, B., Miller, M., Wang, H., van der Merwe, Y., Ho, L., Kostereva, N., Zhang, W., Xiao, B., Davidson, E., Solari, M., Steketee, M. B., Guo, S., Kagemann, L., Wollstein, G., Schuman, J., Chan, K., Gorantla, V. S., Washington, K. M. (2015). Abstract 112: Evaluation of Viability, Structural Integrity and Functional Outcome after Whole Eye Transplantation. ''Plastic & Reconstructive Surgery, 135''(5), 82. "PMC2601300"</ref> investigated the feasibility of eye transplantation by observing the surviving 15 rat models out of the original 22. They were able to confirm the integrity and functional return of vision after whole-eye surgeries with the aid of advance techniques that are available today. The Ear and Eye Foundation of Pittsburgh<ref>'''Ear and Eye Foundation of Pittsburgh''': https://eyeandear.org/our-research/ophthalmology/the-whole-eye-transplant-project</ref> is an organization that is currently running a project with lead researchers to discover a way for the optic nerves to regenerate and to cure blindness by 2020.

===Will the bionic eye pass clinical trials in the next few years?===
[[File:BionicEye.jpg|250px|thumb|left| '''Figure 12.''' Bionic Eye Diagram]]

The bionic eye is an external visual device that has been in the making for the last several years. It hopes to bring back full vision through the aid of a pair of glasses with a camera attached to it, which then transmits high-frequency radio signals to the microchip implanted in the users' eye. These signals are converted into electrical impulses by the electrodes implanted in the chip, which then stimulates the retinal cells and passes through the optic nerve. Electrical impulses travels to the vision processing centres in the brain and these are then interpreted as an image. At the moment, users must learn to understand light flashes and visual patterns and convert them into images they can interpret. Current prototypes require the users to have a previously working eyes, which means their optic nerves must still be relatively healthy and their visual cortex must be developed. Patients who have suffered from retinitis pigmentosa and age-related macular degeneration would benefit this technology. Bionic Vision Australia<ref>'''Bionic Vision Australia''': http://bionicvision.org.au/about/research_plan</ref> is one of the leading organisations that are aiming to treat blindness and are set to perform clinical trials on two of the devices of the bionic eye implants soon. Their objectives are to develop strategies that can improve the affected visual pathway to the brain by stimulating the remaining working retinal cells and also develop safe surgical procedures.

==Glossary==

{| class="pretty table"
|-bgcolor = "DDCEF2"
|'''Term'''
|'''Definition'''
|-bgcolor="FAF5FF"
|'''Age-related macular degeneration'''||An eye disease with its onset usually after age 60 that can progressively destroy the macula, the central portion of the retina, impairing central vision.
|-
|'''Aqueous humour'''||A transparent fluid similar to plasma with low protein concentrations secreted by the ciliary epithelium.
|-
|'''Choroid'''||The pigmented vascular layer of the eye located between the retina and sclera.
|-
|'''Choroid fissure'''||A ventral groove formed by the invagination of the optic cup located at the bottom of the optic vesicle through which blood vessels enter the eye.
|-
|'''Ciliary body'''||The connection between the iris and choroid consisting of the ciliary muscle, ciliary processes and the ciliary ring. Alters the shape of the lens and ciliary epithelium in order to focus on an image.
|-
|'''Cornea'''||The transparent anterior part of the external coat of the eye covering the iris and pupil and continuous with the sclera.
|-
|'''Ectoderm||The outermost primary germ cell layer in the early embryo.
|-
|'''Endoderm||The innermost primary germ cell layer in the early embryo.
|-
|'''Ectodermal placode'''||A neurogenic placode consisting of an area of thickened epithelium in the embryonic head ectoderm layer that gives rise to neurons and other structures of the sensory system.
|-
|'''Extraocular muscles'''||Muscles controlling eye movement.
|-
|'''Fovea'''||A small depression in the retina where visual acuity is the highest.
|-
|'''Hyaloid vasculature'''||The temporary circulatory system in fetal eyes which spontaneously degenerate when the retinal blood vessels begin to develop.
|-
|'''Intraocular pressure'''||Fluid pressure inside the eye created through continued renewal of fluids.
|-
|'''Iris'''||The coloured muscular ring surrounding the pupil which manipulates the diameter and size of the pupil and controls the amount of light entering the eye.
|-
|'''Lens'''||The transparent biconvex structure posterior to the iris with the main function of focusing light onto the retina in order to form clear images of objects at various distances.
|-
|'''Lens pit'''||A pit-like depression in the fetal head where the lens develops.
|-
|'''Lens placode'''||The placode developing in the ectoderm overlying the optic vesicle, eventually becoming the lens of the eye.
|-
|'''Lens vesicle'''||The ectodermal invagination in the embryo formed opposite the optic cup and gives rise to the lens.
|-
|'''Lumina'''||the central cavity of a tubular structure.
|-
|'''Macula'''||An oval-shaped pigmented area where there is the largest density of cone cells and is involved in producing the sharpness of central vision.
|-
|'''Mesenchyme'''||Loosely organised embryonic connective tissue originating from the mesoderm.
|-
|'''Neural crest'''||A temporary group of embryonic ectodermal cells.
|-
|'''Neural retina'''||Refers to three layers of neural cells within the retina (photoreceptor cells, bipolar cells and ganglion cells).
|-
|'''Neural tube'''||A hollow tubular structure as a result of neural plate folding which later develops into the brain and spinal cord.
|-
|'''Neuroepithelium'''||Epithelium consisting of specialised cells which detect sensory triggers for reception of external stimuli.
|-
|'''Optic cup'''||A structure of the diencephalon formed after optic vesicle folding. This structure gives rise to the retina.
|-
|'''Optic groove'''||Two small grooves on each side of the developing forebrain in the neural folds. Also chiasmatic groove.
|-
|'''Optic nerve'''||Cranial nerve II which transmits impulses to the brain from visual information detected by the photoreceptive retina.
|-
|'''Optic stalk'''||Pair of slender embryonic structures that give rise to the optic nerve.
|-
|'''Optic vesicle'''||An evagination of each lateral all of the embryonic vertebrate forebrain from which the nervous structures of the eye develop.
|-
|'''Pupil'''||The central opening in the iris, allowing and regulating the entry of light into the eye.
|-
|'''Retina'''||The sensory membrane that forms the inner lining of the eye containing rods and cones with the main function of photoreception. Nerve impulses in response to visual information are transmitted to the brain via the optic nerve.
|-
|'''Retinitis Pigmentosa'''||A chronic hereditary eye disease characterized by breakdown and loss of cells in the retina leading to progressive visual loss.
|-
|'''Sclera'''||The dense, white, fibrous membrane that, along with the cornea, forms the external protective covering of the eye
|-
|'''Tear film'''||A layer of tears which spreads over the eye, ultimately maintaining the health of the ocular surface by making the external surface smooth and clear.

|}

{{Glossary}}

==References==

<references/>

==External links==

<pubmed>26956898</pubmed>

2017 Group Project 4

2017-10-26T01:24:37Z

Z3416557:

{{ANAT2341Project2017header}}

=Eye Development=

==Introduction==

The eye is a complex sensory structure which allows a variety of species to intake and process visual information from the world around us. Most structures forming the human eye are developed between the embryonic weeks 3 through 10, deriving primarily from ectoderm, neural crest cells and mesenchyme.

This project page will start with a description of the functional anatomy of the adult eye, continue with a description and timeline of the embryonic formation and signaling pathways of important structures of the human eye and animal models and finish with an examination of congenital abnormalities, current research and pending questions for the near future.

We hope that this page provides you with an enjoyable, comprehensive introduction to the embryology of the eye (we have aimed to keep it a concise 'reachable' page!)

==Anatomy of the Adult Eye==

To discuss the key anatomical components of the eye, we will break down the eye in parts<ref>Chen, J., 2011. Handbook of Visual Display Technology. Springer Berlin Heidelberg. Chapter 2.1</ref>:

'''Supporting Structures (Orbit, Extraoccular Muscles, Lacrimal Gland, Eyelid)'''
[[File:22292144 10208413540209536 722417340 o.jpg|250px|thumb|right| '''Figure 1.''' Layers of the Eyeball]]
The orbit consists of a framework of bones and connective tissue which provide structural support and protection to the sensitive human eye. 7 bones contribute to the orbit of the eye: frontal, lacrimal, sphenoid, zygomatic, ethmoid, maxillary, palatine. Several openings exist in the orbital structure, 2 key fissures are the superior orbital fissure and inferior orbital fissure and the posterior optic canal. These openings allow cranial nerves passageway.

A set of 6 extra-ocular muscles allow for a strong voluntary control of the movement of the eye. These muscles include the superior rectus, inferior rectus, lateral rectus, medial rectus, inferior oblique, superior oblique muscles. These muscles are some of the smallest in the human body and are able to produce fast, controlled motion to focus on an object of interest.

The eyelid is the anterior covering of the eye, consisting of a thin fold of skin. It is controlled by the levitator palpebrae superioris muscle. Supero-lateral to the eyelid is the lacrimal gland, which secretes a film of tear, an important component to keeping the anterior surface of the eye moist. The eyelid assists in this process by opening and closing, or blinking, which spreads the tear film across the surface of the eye. Debris caught in the tear film is excreted through the lacrimal duct which is located on the infero-medial surface of the eyelid.
[[File:22251179_10208414266827701_870733039_o.jpg|250px|thumb|right| '''Figure 2.''' Anterior Part of the Eye]]

'''Layers of the Eyeball (Sclera, Choroid, Retina)'''

The superficial layer of the eyeball is the sclera, a thick fibrous layer which thickens as it extends posteriorly. The sclera is visible as the white part of our eye. Its function is to provide structural stability to the eye and serves as attachment site for extra-ocular muscle insertions. Deep to the sclera is the choroid, a vascular network which provides nourishment to the layers of the eyeball and plays a large role in the growth of the eye. Deep to the choroid is the retina, a network of nerve fibres which transmit visual information. The retina contains 2 types of photoreceptors which convert visible light into nerve impulses (rods and cones). Rods work best in low light environments while cones work best in high light enthronements and detect colour and sharp detail.<ref>Curcio CA, Hendrickson AE. Organization and development of the primate photoreceptor mosaic. Prog Ret Ret. 1991;10:89–120.</ref>: The retina does not extend to the anterior part of the eyeball, unlike the sclera and choroid layers.

'''Anterior structure (Lens, Cornea, Pupil, Iris, Ciliary Body, Conjunctiva, Anterior Chamber)'''

The most anterior component of the eyeball is the cornea, which is a multilayered avascular transparent structure. Its major function is to refract incoming light to assist image formation on the retina (contributes about 75% of total refraction). Continuous with the cornea superiorly and inferiorly is the conjunctiva. Deep to the cornea is the iris, the pigmented ring of the eye. The iris consists of 2 muscles which act to enhance and diminish the size of the pupil (the aperture surrounded by the iris) allowing light to enter the eye. Deep to the pupil and iris is the lens, which is a transparent structure which contributes the other 25% of the eye's refractive power. The lens changes shape through accommodation (focusing) controlled by the ciliary body muscles, changing the position of images to form them on the retina. The ciliary body is the anterior extension of the choroid. Between the anterior surface of the lens and posterior surface of the cornea lies the anterior chamber. This chamber is filled with aqueous humour supplied by the ciliary body, which provides nutrients to ocular structures and maintains intra-ocular pressure.
[[File:22251314_10208414283908128_862494115_o.jpg|250px|thumb|right| '''Figure 3.''' Posterior Part of the Eye]]

'''Posterior structure (Optic Nerve, Optic Disc, Macula, Fovea, Posterior Chamber)'''

In the posterior section of the retina is the macula, a central spot in which a high concentration of cone photoreceptors are found. The direct centre of the macula is called the fovea which contains solely cone photoreceptors. The fovea is the only part of the eye which can conduct 'perfect' 20/20 vision. It has a high workload and hence a strong vascular supporting structure<ref><pubmed>6462623</pubmed></ref>:. The most posterior part of the eye is the optic nerve (along with the central retinal artery and central retinal vein), which is responsible for transporting nerve impulses to the cerebral cortex for processing. The opening of the optic nerve is called the optic disc, which contains no photoreceptors and is a blind spot of the eye. Between the posterior surface of the lens, the retina and the optic disc is the posterior chamber. The posterior chamber contains a vitreous humour, a jelly like substance with a high viscosity.

==Embryonic Contributions==

Eye development is a complex process. It involves the formation of the retina and the lens, which we together call the eyeball. It also involves the formation of auxiliary eye structures which are the eyelid, lacrimal gland, and cornea. The retina is formed from the neuroectoderm, the lens from the surface ectoderm and the auxiliary tissues are formed from the head surface ectoderm, neural crest cells and the head mesoderm <ref name="PMC3104407><pubmed>PMC3104407</pubmed></ref>.

[[File:Stage14 sem2cl.jpg|300px|thumb|right| '''Figure 4.''' Stage 14]]

{| class="wikitable"
! style="background:#f4a941" | Embryonic contributions
! style="background:#f4a941" | Eye component
|-
| Neuroectoderm of the forebrain || Retina, Posterior layers of the iris, The optic nerve
|-
| Surface ectoderm of the head || The lens of the eye, The corneal epithelium
|-
| Mesoderm between the neuroectoderm and the surface ectoderm || The fibrous and vascular coats of the eye
|-
| Neural crest cells || Choroid, Sclera, Corneal endothelium
|}

==Timeline of embryonic development==

{| class="wikitable"
! style="background:#f4a941" | WEEK
! style="background:#f4a941" | DEVELOPMENT
|-
| 3-4 || Eye fields, Optic vesicles
|-
| 5-6 || Optic Cup, Lens Vesicle, Choroid Fissure, Hyaloid Artery
|-
| 7-8 || Cornea, Anterior Chamber, Pupillary Membrane, Lens, Retina
|-
| 8-10 || Eyelids
|-
| 9-15 || Iris, Ciliary Body
|}

==Carnegie Stages==

Carnegie Stages are a system of 23 stages used to describe developmental events of the vertebrate embryo. At stage 10 we see early signs related to eye development. The table below is an made of knowledge from Anthony A. Person's article <ref><pubmed>7364662</pubmed></ref>.

{| class="pretty table"
|-bgcolor = "DDCEF2"
|'''Stage'''
|'''Events'''
|-bgcolor="FAF5FF"
|'''Stage 10 (22 days)'''
|The optic primordium has developed. Two small grooves develop on each side of the developing forebrain in the neural folds - this is the optic grooves. The optic placode has begun to develop, which is seen by a small thickening of the surface ectoderm lateral to the hindbrain.
|-
|'''Stage 11 (24 days)'''
|Optic vesicle begins to form from the optic groove.

[[File:Stage11 histology-optic pit.jpg|300px|'''Figure 1.''' Stage 11]]
|-bgcolor="FAF5FF"
|'''Stage 12 (26 days)'''
|The optic vesicles have extended from the forbrain to the surface ectoderm. The optic vesicle now lies close to the surface ectoderm.
|-
|'''Stage 13 (28 days)'''
| The optic vesicle interacts with the surface ectoderm and will induce this ectoderm to form the lens placode, which is the precursor of the lens. Optic evagination differentiation makes it possible to identiy optic parts of retina, future pigmented layer of retina and optic stalk.

[[File:Stage_13_image_060.jpg|300px|'''Figure 2.''' Stage 13]]
|-bgcolor="FAF5FF"
|'''Stage 14 (32 days)'''
| The lens placode is indented by the lens pit and is cup-shaped.
|-
| '''Stage 15 (33 days)'''
| The lens pit will close and form a circle that separates from the surface ectoderm and becomes the lens vesicle. The lens vesicle and optic cub lie close to the surface ectoderm, which creates a slight elevation in the region of the eye.
|-bgcolor="FAF5FF"
| '''Stage 16 (37 days )'''
| The lens body has grown and now has a D-shaped lens cavity. First indication of the development of the eyelids visible as eyelid grooves above and below the eye.
|-
| '''Stage 17 - 19'''
| Retinal pigment is visible and the retinal fissure is almost closed. The eyes are still laterally placed but starts to take a more anterior position. The lower eyelid fold develops first and then the eyelid fold above the eye.
|-bgcolor="FAF5FF"
| '''Stage 18 (44 days)'''
| Mesenchyme invades the region between the lens epithelium and the surface ectoderm. The eyes have shifted to a more anterior position. The groove above and below the eyes are deeper but have not joined yet.
|-
| '''Stage 19 - 22'''
| The eyelid folds develop into the eyelids and the upper and the lower eyelids now meet at the outer canthus, which is the corner of the eye.

[[File:Stage 22 image 208.jpg|300px|'''Figure 3.''' Stage 22]]
|-bgcolor="FAF5FF"
| '''Stage 20 (51 days)'''
| The lens cavity is lost. The upper and lower lids meet laterally and medially. The eyelids now partly cover the eye. Lens suture begins to form.
|-
| '''Stage 23 (57 days)'''
| End of embryonic period. The face begins to look human. Eyelids closure is complete.
|-
|-bgcolor="FAF5FF"
|-
|}

==Development of the eye components==

===Introduction===

<html5media width=“480" height="360">https://www.youtube.com/embed/ghHDFWlfpoQ</html5media>

[[File:DevelopmentEye-PMC43029243.jpg|400px|thumb|right|'''Figure 5.''' Stages of lens formation in mouse embryos]]

The eye starts to develop at 22 days. The optic grooves (sulci) appears in the neural folds at the cranial end of the embryo. When the neural fold fuse to form the forebrain, the optic grooves will form '''optic vesicles'''. The optic vesicles are continuous cavities from the cavity of the forebrain and project from the wall of the forebrain and into the mesenchyme. The optic vesicle extends from the diencephalon and will come in contact with the surface ectoderm of the head. This induces the formation of a lens placode <ref name="Larsen'sHumanEmbryology">Schoenwolf, G.C., Bleyl, S.B., Brauer, P.R., Francis-West, P.H. & Philippa H. (2015). Larsen's human embryology (5th ed.). New York; Edinburgh: Churchill Livingstone.</ref>.

The surface ectoderm near the optic vesicles will thicken and form the '''lens placodes'''. The lens placodes will sink into the surface ectoderm and form '''lens pits'''. The edges of the lens pits will travel towards each other and fuse to form round '''lens vesicles''', which will later lose connection with the surface ectoderm. The optic vesicles do also keep developing - they will form double-walled '''optic cups''' which are connected to the brain by the '''optic stalk'''. The two layers of the optic cup will differentiate in different directions. The cells of the outer layer will produce melanin pigment and later become the '''pigmented retina'''. The cells of the inner layer of the optic cup will proliferate fast and develop glia, ganglion cells, interneurons and light-sensitive photoreceptor neurons. These cells are in the '''neural retina'''. The ganglion cells of the retina are neurons that send signals to the brain. The axons of the ganglion cells of the neural retina will grow in the wall of the optic stalk. The cavity in the optic nerve will start disappearing, and instead, the axons of the ganglion cells will form the '''optic nerve'''. The optic stalk is now the optic nerve <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>

The optic cups will fold inwards around the lens while the lens vesicles have grown inwards so they have fully lost their connection with the surface ectoderm, which locates them in the cavities of the optic cups. The retinal fissures (linear grooves) will develop and cover the ventral surface of the optic cups and down to the optic stalk. The retinal fissures contain vascular mesenchyme and hyaloid blood vessels will develop here. The hyaloid artery supplies the structures in the eye with blood and the hyaloid vein will return the blood from these structures <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

'''Formation of the optic vesicle'''

It is a specific area of the neural ectoderm that will become the optic vesicle - this happens because of a group of transcription factors - Six3, Pax6, and Rx1. These transcription factors are expressed in the most anterior tip of the neural plate. This area will split into bilateral regions and form the optic vesicles. The Pax6 protein has shown to be especially important for the development of the lens and retina. This protein is important for photoreceptive cells in all phyla. Pax 6 is also present in the murine forebrain, hindbrain, and nasal placodes, but the eyes are most sensitive its absence <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

The sonic hedgehog gene is important for the separation of the single eye field into two fields. If this gene is inhibited, the eye field will not split which will result in cyclopia, a single eye in the center of the face <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

===Retina===

[[File:Bailey463.jpg|400px|thumb|right|'''Figure 6.''' Diagram of developing lens and optic cup]]

The retina is the essential component of the eye with the primary function of photoreception <ref><pubmed>7084144</pubmed></ref>. Formation of the retina begins with the specification of retinal cells in the anterior neuroectoderm. First morphological sign of eye development is the formation of two lateral grooves in the anterior neuroectoderm, which is called the optic sulci. The cells of the optic sulci will evaginate and form the optic vesicle. The distal portion of the optic vesicle will form the retina and the proximal will form the optic stalk <ref><pubmed>18675797 </pubmed></ref>. The retina develops from the walls of the optic cup, these walls develop into the two layers of the retina. The thin, outer layer of the optic cup will become the pigment layer of the retina and the thick, inner layer of the optic cup will differentiate into the neural retina. Forkhead transcription factors are regulating the proliferation and differentiation of the retinal precursor cells. During the embryonic and early fetal periods, the two layers of the retina are separated which makes an intraretinal space. The intraretinal space is derived from the cavity of the optic cup. The two layers of the retina will fuse and the intraretinal space will gradually disappear <ref name="Larsen'sHumanEmbryology">Schoenwolf, G.C., Bleyl, S.B., Brauer, P.R., Francis-West, P.H. & Philippa H. (2015). Larsen's human embryology (5th ed.). New York; Edinburgh: Churchill Livingstone.</ref>.

When the lens is developing the inner layer of the optic cup starts to proliferate and forms a thick neuroepithelium which will later differentiate into the neural retina. The neural retina contains photoreceptors and the cell bodies of neurons and is the light-sensitive region of the retina. The axons of the ganglion cells in the neural retina grow in the wall of the optic stalk and will form the optic nerve <ref name="Larsen'sHumanEmbryology">Schoenwolf, G.C., Bleyl, S.B., Brauer, P.R., Francis-West, P.H. & Philippa H. (2015). Larsen's human embryology (5th ed.). New York; Edinburgh: Churchill Livingstone.</ref>.

===Lens===

Human lens induction occurs at around 28 days and is completed around day 56. The surface ectoderm will thicken near the optic vesicle and create the lens placode and later form the lens vesicle <ref><pubmed>20171212 </pubmed></ref>. Lens cells come from ectoderm and differentiate into either lens fibers or the lens epithelium. The anterior monolayer of epithelial cells of the lens will create the lens epithelium, which makes the sheet of cuboidal epithelium covering the anterior surface of the lens. The posterior lens vesicle cells will produce the linear primary fibre cells aligned parallel to the optic axis. These fibres will create the lens mass and form the embryonic lens nucleus. The lens epithelial cells will keep proliferating and produce new cells which generate a secondary lens fiber cells. This rows of cell will form the outer shells and keep the lens growing throughout life. This makes the eye lens unique - it will have an addition of new cells inside the surrounding capsule all the time <ref><pubmed>25406393</pubmed></ref>.

===Ciliary Body===

The ciliary body is a muscular and secretory tissue and is located directly behind the lens. The ciliary body forms part of the anterior segment of the eye and is an important regulator of eye physiology and the vision. The ciliary body produces the aqueous fluid which fills the eyes and nourishes the lens and cornea - this aqueous fluid function to keep the eye in a pressurized and inflated state, which is important the vision.The ciliary body also synthesizes collagenIX and tenasin-C <ref><pubmed>17275804</pubmed></ref>.

The ciliary body extends from the iris root (anteriorly) to the ora serrata (posteriorly). It consist of ciliary muscles and ciliary processes. Each ciliary process (fold) is covered by a double-layered secretory epithelium; the outer pigmented and the inner unpigmented (closes to the lens). The epithelial layers of the ciliary body comes from the retina of the optic cup. We see two different ciliary body epithelium: the inner non-pigmented ciliary epithelium which is connected with the neural retina and the outer pigmented ciliary epithelium which is connected with the retinal pigmented epithelium. The epithelium of the iris is the further anterior extension. The epithelial layers are associated with a stroma containing the ciliary muscle. The ciliary muscle is complex, but can be divided into three portions; anterior, posterior and internal <ref><pubmed>12127103</pubmed></ref>.

In the chick eye development, we see the mesenchyme grow together on the margin of the optic cup and will form the stroma of the ciliary body and the iris, which is located more anteriorly. It is unknown how if the lens has a role in inducing the secretory ciliary body epithelium and the muscular iris epithelium <ref><pubmed>17275804</pubmed></ref>.

===Iris===

The iris is the circular, pigmented muscular portion of the eye with a central aperture that is the pupil. The main function of this round muscle is to manipulate pupil diameter as an adjustment to various conditions and to control the amount of light entering the eye <ref name=’’21413392’’><pubmed>21413392</pubmed></ref>. This is influenced by dilator pupillae (radial) and sphincter pupillae (constricting) muscles. Iris pigmentation is dependent on the abundance and distribution of certain types of melanin in the posterior epithelium of the iris (eumelanin and pheomelanin) <ref name=’’21413392’’/>.

The Iris develops at the end of the third month of development. The iris is a thin layer and derives from the anterior rim of the optic cup <ref><pubmed>22219630</pubmed></ref>. The iris is formed by the pigment-containing internal and external layers of the optic cup and by a layer of vascularised connective tissue which also contains the pupillary muscles. Internal layers of the optic cup form the non-pigmented iris parts whereas the external layers of the optic cup develop into the pigmented epithelial structures. <ref name=’’18168498’’><pubmed>18168498</pubmed></ref>. Iris stroma develops as a result of neural crest cell migration – within this stroma, the dilator and constrictor muscles develop from the neuroectoderm of the optic cup. In the anterior of the eye, the optic epithelium is non-neural and matures as ciliary body and iris epithelia <ref name=’’18168498’’/>.

===Cornea===

The cornea is the unique, transparent and avascular component located at the most anterior section of the eye. It is composed of five layers stemming from the 3 main layers of epithelium, stroma and endothelium:

* Corneal epithelium (most anteriorly) – consisting of multiple layers of cells which rest on a basement membrane.
* Bowman’s membrane – a clear, acellular homogenous layer. This layer is a modified portion of the stroma and has no regenerative capacity as a response to damage <ref name=''7084144''><pubmed>7084144</pubmed></ref>.
* Corneal stroma – largest portion of the retina consisting of collagenous tissue.
* Descemet’s membrane – a homogenous, elastic true basement layer with a regenerative capacity.
* Corneal endothelium – a single layer of cuboidal cells responsible for the maintenance of the dehydrative nature of corneal tissue. <ref name=''7084144''/>.

Corneal development involves interactions between ectoderm-derived tissues. More specifically, the corneal epithelium arises from interactions between the cranial ectoderm and optic vesicles derived from the neural ectoderm <ref name=''26310148''><pubmed>26310148</ref></pubmed>. The neural tube and the adjacent ectoderm give rise to the neural crest cells which are multipotent with a migratory capacity. These cells contribute to the formation of corneal epithelium and the stromal cells. Innervation of the cornea stroma and epithelium is derived from both the neural crest and the ectodermal placode <ref name=''26310148''/>. The endothelium is comprised of differentiated neural crest cells which contribute to the later formation of Descemet’s membrane <ref><pubmed>6511224</pubmed></ref>.

===Aqueous Chambers===

There are two aqueous chambers of the eye: anterior and poster. These chambers are filled with a plasma-like fluid called aqueous humour and is produced by the ciliary body and trabecular meshwork in 3 main stages: diffusion, ultrafiltration and active secretion <ref><pubmed>6763801</pubmed></ref>. The main function of this fluid is to maintain the intraocular pressure as well as provide structural integrity to the round shape of the eyeball. This structure also has a role in the immune response and provides nutrition to the avascular tissue (e.g., the cornea and lens). <ref><pubmed>21293732</pubmed></ref>.

The anterior chamber is defined as the developed space posterior to the cornea (between the cornea and the iris) and develops at the stage of differentiation of the mesodermal portion of the iris <ref name=’’18168498’’/>. The space defining the posterior chamber develops as the mesenchyme between the lens and the peripheral iris.

===Choroid and Sclera===

The choroid and sclera are both surround the eye and are located adjacent to each other (the choroid lines the inner portion of the sclera). The sclera is the outer, fibrous white layer of the eye which functions as a supportive wall of the eye ball and is continuous with the cornea <ref name=''7084144''/> . The heavy vasculature of the choroid provides a major supply of oxygen and nourishment to the retina <ref><pubmed>20044062</pubmed></ref>.
They are derived from interactions between the neural crest and mesoderm-derived mesenchyme. The sclera forms as a result of condensation of the mesenchyme outside the optic cup <ref><pubmed>1628748</pubmed></ref>.
The choroid arises from the mesenchyme surrounding the optic vesicle and the cranial neural crest cells. The first vasculature structures appear in the choroid during week 15 in the form of arterioles and venules; veins and arteries become distinguishable by week 22 <ref name=’’2199235’’><pubmed>2199235</pubmed></ref>.

===Extraocular muscles===

The extraocular muscles are responsible for eye movement within the eye orbit – a critical aspect of sight and communication. 6 main muscles contribute to eye movement. These include: superior rectus, inferior rectus, lateral rectus, medial rectus, superior oblique and inferior oblique.

The development of these muscles is dependent on interactions between the eye, its muscles and the neural crest. <ref name=''21482859''><pubmed>21482859</pubmed></ref>.
Somites supplied by cranial nerve III forms 5 of the 6 extraocular muscles which form an interlocking tendinous ring made of fibrous connective tissue. The 5 muscles include the lateral, medial, superior and inferior rectus, and the superior oblique muscle. This common tendinous ring is known as the annulus of Zinn and surrounds the entry of the optic nerve. The remaining sixth muscle is the inferior oblique muscle and is separate from the aforementioned tendinous ring due to its distinct point of origin. <ref name=''21482859''/>.

===Eyelids===

The eyelids are upper and lower folds of skin functioning as a barrier protecting the anterior surface of the eye from direct local injury. Eyelids also regulate light exposure, distribute precorneal tear film over the corneal surface when blinking and are involved in functions involving tear flow <ref><pubmed>1993591</pubmed></ref>.
No sign of eyelid fold development is evident at week 5 however at this stage the lens pit begins to invaginate from the surface ectoderm <ref name=’’27124372’’><pubmed>27124372</pubmed></ref>. Week 6 initiates the timeline of eyelid development as small depressions emerge in the surface ectoderm both above and below the developing eye – these rapidly deepen to form the folds of the eyelids <ref name=‘’7364662’’><pubmed>7364662</pubmed></ref>. The lower eyelid fold develops first and, by the end of week 6, the lower fold is more distinct than the upper eyelid fold <ref><pubmed>21416630</pubmed></ref>. Week 7 marks the point at which both the upper and lower folds are distinctly developed and during this stage, the upper lid assumes its more dominant role <ref name=’’27124372’’/>. The eyelid is not fully closed - there is a gap between the folds and the cornea is slightly visible – they eventually undergo fusion in week 8 <ref name=’’27124372’’/>.

===Lacrimal Glands===

The lacrimal glands are exocrine glands located in the upper lateral region of each eye orbit which secrete the aqueous potion of the tear film. This film is continuously secreted and functions to clean and protect the external surface of the eye, keeping the environment constantly moist and preventing possible injury from dust and other particles <ref><pubmed>17001201</ref>.
Lacrimal gland morphogenesis is identified in three stages.

* The first is the presumptive glandular stage. This stage involves the thickening of the conjunctival superior fornix epithelium and the condensing of the surrounding mesenchyme <ref name=’’14635806’’><pubmed>14635806</pubmed></ref>.

* The second is the bud stage. This stage is considered the initial sign of glandular formation due to the development of nodular structures and lumina within epithelia buds <ref name=’’14635806’’/>.

* The third is the glandular maturity stage (week 9-16). In this stage, the lacrimal gland begins to morphologically mirror the adult gland <ref name=’’14635806’’/>.

==Signalling pathways and transcription factors involved throughout eye development==

===Eye field development===

Many signalling pathways and transcription factors are involved in the development of the eye field (which forms in addition to the telencephalon and diencephalon as part of division of the anterior neural plate). Eye progenitor cells are guided into the eye field region by fibroblast growth factor, bone morphogenetic protein and Wnt-signalling pathways <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>. Additionally, interactions between canonical and non-canonical Wnt-signalling have been shown to maintain the eye field border <ref name=’’16413771’><pubmed>16413771</pubmed></ref>.

The cells of the eye field express eye field transcription factors, some of which include Rx1/Rax, Pax6, Lhx2, Six3 and Otx2. Six3, Pax6, Otx2 and Rx1 specify retinal lineage and regulate progenitor cell movement to guide them to their correct locations <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>. Six3 also partly mediates Wnt-signalling repression, allowing for the development of the optic vesicles from the eye field <ref name=’’23684892 ’’><pubmed>23684892 </pubmed></ref>. Lhx2 maintains optic lineage in eye progenitor cells and suppresses the potential for differentiation towards different fates <ref name=’’23595746’’><pubmed>23595746</pubmed></ref>.

===Eye field division and progression to optic cup===

TGF-β, FGF and Shh family factors secreted by the axial mesoderm underlying the eye field initiate its splitting into two bilateral, symmetric eye primordia <ref name=’’23684892 ’’><pubmed>23684892 </pubmed></ref>. These factors also regulate the expression of transcription factors Pax2, Pax6, Vax1 and Vax2, thereby establishing the boundaries and patterning the proxiodistal and ventronasal axes of the optic vesicles <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>.

Despite the close relationship between cellular proliferation and morphogenesis, optic vesicle evagination does not appear to be mainly driven by proliferation <ref name=’’23684892 ’’><pubmed>23684892 </pubmed></ref>. Alternatively, it has been shown that retinoic acid has critical importance in optic vesicle evagination to form the optic cup <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>. Rx3 activity has also been observed to have involvement in optic vesicle evagination <ref name=’’23684892 ’’><pubmed>23684892 </pubmed></ref>.

===From optic cup to developed eye===

Lens placode maturation and lens development is dependent on Pax6 expression and regulation. During placode formation bone morphogenetic protein and fibroblast growth factor signalling regulate Pax6. Within the presumptive lens ectoderm, Pax6 is regulated by Six3 and Meis. However, within the presumptive epithelium Pax6 is a regulating factor, regulating the expression of Sox2 and eventually Six3 once the lens placode is formed <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>.

Meanwhile, in the primordial retina retinal progenitor cells become retinal ganglion cells through the expression of the basic helix-loop-helix transcription factor ath5 (which is regulated by Hh and Fgf signalling. The amacrine, horizontal and bipolar cells of the retina are generated by a variety of transcription factors, some of which include Pax6, Six3 and Foxn4 <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>. Crx and Otx2 positive cells progress towards photoreceptor fates and are further developed into rods and cones based on specific transcription factor expression (TRβ2 and RxRγ expression is required for cones, where as Nrl, Nr2e3 and Ascl1 expression is required for rods) <ref name=’’20648062’’><pubmed>20648062</pubmed></ref>. The transcription factors required for the development of the retinal pigment epithelium include Mitf, Otx1/Otx2 and Pax6. TGF-β, FGF, BMP and Hh signalling from the surrounding mesenchyme have also been shown to help induce retinal pigment epithelium fate in progenitor cells <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>.

Within the choroid, the expression and regulation of many different factors and signalling pathways is required for the development of proper arterial-venous connections, allowing for the functional circulation of nutrients and oxygen throughout the eye. VEGF, bFGF, PDGF and PEDF (from the retinal pigment epithelium) drive the development and maturation of choroidal blood vessels. Vascular patterning is regulated by the interactions between VEGF and Delta-like 4 factors. Additionally, Notch signalling has been shown to have importance in the formation of capillary beds <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>.

===Eye formation in the absence of the retina===

The gene Rx is a key component in the formation of retinal structures. Studies have shown that mice lacking Rx function do not form optic sulci or optic vesicles and do not have retina-specific gene expression. There has been made studies in human, medaka, zebrafish and Xenopus which suggest that Rx genes are required for the formation of the vertebrate retina. It is also shown that in Rx-deficient mouse embryos the mature lens does not develop. This indicates that retinal cells are necessary for lens formation, and if the mouse is lacking Rx gene, then it will not display any retina-specific gene expression <ref name="PMC3104407"/>.

It is thought that signaling from the optic vesicle is important to activate the lens-specific gene and the formation of the lens placode. If there are no retinal cells generated, then the morphogenesis of the optic cup does not take place and the lens will not form. The study also showed that elimination of β-catenin expression in the head surface ectoderm in Rx-deficient embryos would develop a lens-like structure even though there were no optic vesicle/cup. Elimination of β-catenin lead to upregulation of Pax6, which is a gene that has a key role in lens formation. This indicates that the optic vesicle/cup might not be required for lens formation. The lens developed smaller than in wild type embryos, which means that the optic cup/vesicle might have an effect on a determination of the size of the lens. It could be that the developing optic vesicle/cup shields the developing lens placode from signals for other tissues that could disturb the lens formation <ref name="PMC3104407"/>.

It is not fully understood if the formation of the auxiliary eye structures is dependent on the development of the eyeball and its components, the retina and the lens. A study made my Eric C. Swindell and al. showed that auxiliary eye structures form even in the absence of retinal morphogenesis and retina-specific gene expression. This indicates that there are two separate developmental processes involved in the formation of the eye and its associated structures. In the absence of the retina and the lens, we still see specific gene expression in the surface ectoderm initiating the formation of auxiliary eye structures like eyelids and lacrimal glands <ref name="PMC3104407"/>.

==Current research==

===Iris epithelium cells as a potential source for regenerative medicine for retinal pigment epithelium degeneration===

The retinal pigment epithelium (RPE) is a monolayer of neural-crest-derived cells and is located between the photoreceptors and the choroid. There are many disorders that involve dysfunctional RPE and leads to retinal degenerative diseases. There is no treatment for these diseases, therefore, one of the most promising future therapy for RPE related disorders is to replace the cells of the dysfunctional RPE <ref name="PMC5565104><pubmed>PMC5565104</pubmed></ref>..

Studies have focused on the development and use of induced pluripotent stem cells (iPSC) for cell replacement therapy. It is possible to differentiate iPSC in vitro towards RPE cells and use them for experimental transplantation studies in animal models. But an alternative strategy for a retinal replacement is based on transdifferentiation (direct conversion) and involves transforming an adult somatic cell into another adult somatic cell. Use of overexpression of cell-lineage specific genes can convert one cell into another cell type and skip the pluripotent state. Iris epithelium (IE) cells might be able to be transdifferentiated into the RPE since both RPE and IE are neuro-epithelia and has a common embryological origin - they both derive from neuroectoderm of the developing optic cup <ref name="PMC5565104"/>.

A study made by Anna Bennis et al. <ref name="PMC5565104"/>. has shown that the canonical pathways for the most highly expressed genes of the IE and the RPE were very similar. Wnt signaling pathways has shown to be active in the IE but not in the RPE. The Wnt signaling pathway consists of a group of signal transduction pathways that has an influence on cell fate determination and cell proliferation during embryonic development. Activation of Wnt SP makes it possible to reprogram somatic cells (also retinal neurons) into iPSC and is important for the differentiation of pluripotent stem cells to RPE cells. The high expression of Wnt SP genes in the iE suggests that the IE has a multipotent character during life and therefore could be transformed into RPE cells used for RPE replacement <ref name="PMC5565104"/>.

===Developing Retinal Ganglion Cells from Pluripotent Cells===

A 2016 paper <ref>Ohlemacher, S. K., Sridhar, A., Xiao, Y., Hochstetler, A. E., Sarfarazi, M., Cummins, T. R. and Meyer, J. S. (2016), Stepwise Differentiation of Retinal Ganglion Cells from Human Pluripotent Stem Cells Enables Analysis of Glaucomatous Neurodegeneration. Stem Cells, 34: 1553–1562. doi:10.1002/stem.2356<ref/> addressed the difficulty of culturing retinal ganglion cells (RCG) from pluripotent cells (both embryonic and enducded) due to a lack of known specific markers to communicate the cell to develop into a RCG. This study found a method of dveloping RCG through a stepwise approach involving retinal progentior cells. The RCG cells created showed no functional difference that normal RCG cells. Applications of this discovery have included helping to treat patients with congential glaucoma abnormalities
===UNSW Optometry and Vision Science Current Projects===

Additionally, UNSW has a number of current research projects currently being undertaken <ref>https://www.optometry.unsw.edu.au/research/current-research</ref>

A few interesting topics include:

- Biochemical changes in the tear film in relationship to the corneal structural changes in diabetes so as to be able to predict nerve damage earlier

- The use of video games and virtual reality (visual electrophysiology) to help treat some congenital anomalies such as lazy eye

- How retinal circuitry operates with regards to neurotransmitter release, receptor location and receptor function, allowing the development of a retinal roadmap which can be applied to retinal diseases

==Animal Models==
The zebrafish species is used to investigate ocular development, function and disease due to having the same morphology as other vertebrates including humans. The advantages of zebrafish include: they are able to quickly reach their sexual maturity, they behaviour can be observed quite early on because of their rapid development and most importantly, their embryos are translucent. Zebrafish is also active during the day therefore their retina contains a large number of diverse cone subtypes in additions to rods. <ref name="Zebrafish"> Glass, A. S. & Dahm, R. (2003). The Zebrafish as a Model Organism for Eye Development. ''Opthalmic Research, 36''(1), 4-24. doi: 10.1159/000076105</ref>

[[File:Chokh.png|250px|thumb|left| '''Figure 11.''' Wild type zebrafish vs chokh/rx3 knockout. Morphological differences with the absence of eyes in the knockout.]]
Through studying zebrafish, it was found that that a mutation in ''chokh/rx3'' gene results in the absence of eyes during the earliest stages of development due to failure of the retinal progenitor cells. <ref name="chokh">Loosli, F., Staub, W., Finger-Baier, K. C., Ober, E. A., Verkade, H., Wittbrodt, J. & Baier, H. (2003). Loss of eyes in zebrafish caused by mutation of chokh/rx3. ''EMBO Reports, 4''(9), 894-899. doi: 10.1038/sj.embor.embor919 </ref>. Optical vesicle is turned inside out and the neuronal differentiation is blocked. In this study, they have found that the DNA-binding homeodomain and the the entire C-terminal portion led to a nonsense mutation that resulted to complete loss of function in the eye. It was concluded that the gene ''chokh/rx3'' is important for the developing optic primordia.

==Congenital Abnormalities==
Although quite rare, abnormalities can occur during the embryonic development that causes serious effects to the features of the eyes, its function as well as the further normal development after birth. These abnormalities can occur unilaterally or bilaterally and it is also common for most reported cases to have more than one type of eye abnormalities at a time. Thus, the estimated prevalence statistics listed in the table can overlap.

{| class="wikitable"
! style="background:#f4a941" | Congenital Anomalies
! style="background:#f4a941" | Description
! style="background:#f4a941" | Epidemiology
|-
| Anopthalmia || The absence of the eyes.
| rowspan="2" | Prevalence: Anophthalmia-Microphthalmia Syndrome was estimated to be 5.3 per 100 000 cases <ref name="Anophthalmia">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: [[http://www.orpha.net/consor/cgi-bin/index.php]] </ref>
Cause: SOX2 gene mutation <ref name="SOX2 Gene"> Mauri, L., Franzoni, A., Scarcello, M.,
Sala, S., Garavelli, L. Modugno, A., ... Penco, S. (2015). SOX2, OTX2 and PAX6 analysis in subjects with anophthalmia and microphthalmia. ''European Journal of Medical Genetics, 58'', 66-70. doi: 10.1016/j.ejmg.2014.12.005 </ref>
|-
| Microphtalmia || Abnormal reduction in size of the eyeballs.
|-
| Keratoglobus || Structural abnormalities in the formation of the cornea - unknown cause - fixable through surgery<ref name="PMID23807384"><pubmed>23807384</pubmed></ref>
| Prevalence: understood to be a rare condition<ref name="PMID23807384"><pubmed>23807384</pubmed></ref>
|-
| Ptosis ('Lazy Eye')|| Structural abnormalities in the eyelid, can be congenital - specifically the failure of innervation of the oculomotor nerve for levator palpebrae superioris <ref name="PMID8759493"><pubmed>8759493</pubmed></ref> - fixable through surgery
| Prevalence: a relatively well known abnormality
|-
| Aphakia || Te absense of a lens in the eye, causing a loss of accommodation and hence far-sightedness. People with aphakia have relatively small pupils which are unable to dilate as much <ref name="PMID28913511"><pubmed>28913511</pubmed></ref>
| Prevalence: a rare congenital abnormality
|-
| Coloboma || A condition where parts of the eye is missing and failed to develop normally.
| Prevalence: Occular coloboma was estimated to be 8.0 per 100 000 cases <ref name="Anophthalmia">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: [[http://www.orpha.net/consor/cgi-bin/index.php]] </ref>
|-
| Aniridia || Complete or partial absence of the iris.
| Prevalence: Estimated to be 1.5 per 100 000 cases <ref name="Anophthalmia">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: [[http://www.orpha.net/consor/cgi-bin/index.php]] </ref>
|-
| Optic Nerve Hypoplasia || A condition where the optic nerves are underdeveloped.
| Prevalence: Reported to be the most common abnormality <ref name="The Optic Nerve Hypoplasia">Ryabets-Lienhard, A., Stewart, C., Borchert, M., & Geffner, M. E. (2016). The Optic Nerve Hypoplasia Spectrum - Review of the Literature and Clinical Guidelines. ''Advances in Pediatrics, 63'', 127-146. doi: 10.1016/j.yapd.2016.04.009 </ref>
*10.9 per 100 000 in United Kingdom
*17.3 per 100 000 cases in Sweden.
*6.3% of cases was reported in New Zealand
|-
|}

<gallery>

Anophthalmia.jpeg|'''Figure 8.''' Anopthalmia
Microphthalmia-500px.jpg| '''Figure 9.''' Microphthalmia
Opac_figure_7.jpg| '''Figure 10.''' Iris Coloboma
Opac figure 10.jpg| '''Figure 11.''' Partial Aniridia
</gallery>

==Future questions==
===Will it be possible to have eye transplants in the future?===
Lots of research has been done in making a whole-eye transplantation successful in order to finally cure blindness. Blindness is a worldwide problem and is currently untreatable due to the fact that retinal ganglion cells and the optic nerves do not regenerate. This can result from diseases including macular degeneration and end of stage glaucoma. The first successful eye transplantation was led by Stone and Cole in 1943<ref name="Return of Vision"> Stone, L. S. & Cole, C. H. (1943). Grafted Eyes of Young and Old Adult Salamanders (Amblystoma Punctatum) Showing Return of Vision. ''Yale Journal of Biology and Medicine, 15''(5), 735-754.2. PMCID: PMC2601300</ref> investigating 104 samples of the salamander species, ''Amblystoma Punctatum'', and one of its eyes were either implanted back into the same animal or it was completely transplanted to a new host. It was reported that circulation in the iris was re-established, retina was able to regenerate, a new optic nerve was connected to the brain through the optic chiasma and ocular movements were regained. Vision was reestablished by the second month. In a more recent study, in 2015, Li et al.<ref name="Structural Integrity"> Li, Y., Komatsu, C., Wang, B., Miller, M., Wang, H., van der Merwe, Y., Ho, L., Kostereva, N., Zhang, W., Xiao, B., Davidson, E., Solari, M., Steketee, M. B., Guo, S., Kagemann, L., Wollstein, G., Schuman, J., Chan, K., Gorantla, V. S., Washington, K. M. (2015). Abstract 112: Evaluation of Viability, Structural Integrity and Functional Outcome after Whole Eye Transplantation. ''Plastic & Reconstructive Surgery, 135''(5), 82. "PMC2601300"</ref> investigated the feasibility of eye transplantation by observing the surviving 15 rat models out of the original 22. They were able to confirm the integrity and functional return of vision after whole-eye surgeries with the aid of advance techniques that are available today. The Ear and Eye Foundation of Pittsburgh<ref>'''Ear and Eye Foundation of Pittsburgh''': https://eyeandear.org/our-research/ophthalmology/the-whole-eye-transplant-project</ref> is an organization that is currently running a project with lead researchers to discover a way for the optic nerves to regenerate and to cure blindness by 2020.

===Will the bionic eye pass clinical trials in the next few years?===
[[File:BionicEye.jpg|250px|thumb|left| '''Figure 12.''' Bionic Eye Diagram]]

The bionic eye is an external visual device that has been in the making for the last several years. It hopes to bring back full vision through the aid of a pair of glasses with a camera attached to it, which then transmits high-frequency radio signals to the microchip implanted in the users' eye. These signals are converted into electrical impulses by the electrodes implanted in the chip, which then stimulates the retinal cells and passes through the optic nerve. Electrical impulses travels to the vision processing centres in the brain and these are then interpreted as an image. At the moment, users must learn to understand light flashes and visual patterns and convert them into images they can interpret. Current prototypes require the users to have a previously working eyes, which means their optic nerves must still be relatively healthy and their visual cortex must be developed. Patients who have suffered from retinitis pigmentosa and age-related macular degeneration would benefit this technology. Bionic Vision Australia<ref>'''Bionic Vision Australia''': http://bionicvision.org.au/about/research_plan</ref> is one of the leading organisations that are aiming to treat blindness and are set to perform clinical trials on two of the devices of the bionic eye implants soon. Their objectives are to develop strategies that can improve the affected visual pathway to the brain by stimulating the remaining working retinal cells and also develop safe surgical procedures.

==Glossary==

{| class="pretty table"
|-bgcolor = "DDCEF2"
|'''Term'''
|'''Definition'''
|-bgcolor="FAF5FF"
|'''Age-related macular degeneration'''||An eye disease with its onset usually after age 60 that can progressively destroy the macula, the central portion of the retina, impairing central vision.
|-
|'''Aqueous humour'''||A transparent fluid similar to plasma with low protein concentrations secreted by the ciliary epithelium.
|-
|'''Choroid'''||The pigmented vascular layer of the eye located between the retina and sclera.
|-
|'''Choroid fissure'''||A ventral groove formed by the invagination of the optic cup located at the bottom of the optic vesicle through which blood vessels enter the eye.
|-
|'''Ciliary body'''||The connection between the iris and choroid consisting of the ciliary muscle, ciliary processes and the ciliary ring. Alters the shape of the lens and ciliary epithelium in order to focus on an image.
|-
|'''Cornea'''||The transparent anterior part of the external coat of the eye covering the iris and pupil and continuous with the sclera.
|-
|'''Ectoderm||The outermost primary germ cell layer in the early embryo.
|-
|'''Endoderm||The innermost primary germ cell layer in the early embryo.
|-
|'''Ectodermal placode'''||A neurogenic placode consisting of an area of thickened epithelium in the embryonic head ectoderm layer that gives rise to neurons and other structures of the sensory system.
|-
|'''Extraocular muscles'''||Muscles controlling eye movement.
|-
|'''Fovea'''||A small depression in the retina where visual acuity is the highest.
|-
|'''Hyaloid vasculature'''||The temporary circulatory system in fetal eyes which spontaneously degenerate when the retinal blood vessels begin to develop.
|-
|'''Intraocular pressure'''||Fluid pressure inside the eye created through continued renewal of fluids.
|-
|'''Iris'''||The coloured muscular ring surrounding the pupil which manipulates the diameter and size of the pupil and controls the amount of light entering the eye.
|-
|'''Lens'''||The transparent biconvex structure posterior to the iris with the main function of focusing light onto the retina in order to form clear images of objects at various distances.
|-
|'''Lens pit'''||A pit-like depression in the fetal head where the lens develops.
|-
|'''Lens placode'''||The placode developing in the ectoderm overlying the optic vesicle, eventually becoming the lens of the eye.
|-
|'''Lens vesicle'''||The ectodermal invagination in the embryo formed opposite the optic cup and gives rise to the lens.
|-
|'''Lumina'''||the central cavity of a tubular structure.
|-
|'''Macula'''||An oval-shaped pigmented area where there is the largest density of cone cells and is involved in producing the sharpness of central vision.
|-
|'''Mesenchyme'''||Loosely organised embryonic connective tissue originating from the mesoderm.
|-
|'''Neural crest'''||A temporary group of embryonic ectodermal cells.
|-
|'''Neural retina'''||Refers to three layers of neural cells within the retina (photoreceptor cells, bipolar cells and ganglion cells).
|-
|'''Neural tube'''||A hollow tubular structure as a result of neural plate folding which later develops into the brain and spinal cord.
|-
|'''Neuroepithelium'''||Epithelium consisting of specialised cells which detect sensory triggers for reception of external stimuli.
|-
|'''Optic cup'''||A structure of the diencephalon formed after optic vesicle folding. This structure gives rise to the retina.
|-
|'''Optic groove'''||Two small grooves on each side of the developing forebrain in the neural folds. Also chiasmatic groove.
|-
|'''Optic nerve'''||Cranial nerve II which transmits impulses to the brain from visual information detected by the photoreceptive retina.
|-
|'''Optic stalk'''||Pair of slender embryonic structures that give rise to the optic nerve.
|-
|'''Optic vesicle'''||An evagination of each lateral all of the embryonic vertebrate forebrain from which the nervous structures of the eye develop.
|-
|'''Pupil'''||The central opening in the iris, allowing and regulating the entry of light into the eye.
|-
|'''Retina'''||The sensory membrane that forms the inner lining of the eye containing rods and cones with the main function of photoreception. Nerve impulses in response to visual information are transmitted to the brain via the optic nerve.
|-
|'''Retinitis Pigmentosa'''||A chronic hereditary eye disease characterized by breakdown and loss of cells in the retina leading to progressive visual loss.
|-
|'''Sclera'''||The dense, white, fibrous membrane that, along with the cornea, forms the external protective covering of the eye
|-
|'''Tear film'''||A layer of tears which spreads over the eye, ultimately maintaining the health of the ocular surface by making the external surface smooth and clear.

|}

{{Glossary}}

==References==

<references/>

==External links==

<pubmed>26956898</pubmed>

2017 Group Project 4

2017-10-26T01:16:50Z

Z3416557:

{{ANAT2341Project2017header}}

=Eye Development=

==Introduction==

The eye is a complex sensory structure which allows a variety of species to intake and process visual information from the world around us. Most structures forming the human eye are developed between the embryonic weeks 3 through 10, deriving primarily from ectoderm, neural crest cells and mesenchyme.

This project page will start with a description of the functional anatomy of the adult eye, continue with a description and timeline of the embryonic formation and signaling pathways of important structures of the human eye and animal models and finish with an examination of congenital abnormalities, current research and pending questions for the near future.

We hope that this page provides you with an enjoyable, comprehensive introduction to the embryology of the eye (we have aimed to keep it a concise 'reachable' page!)

==Anatomy of the Adult Eye==

To discuss the key anatomical components of the eye, we will break down the eye in parts<ref>Chen, J., 2011. Handbook of Visual Display Technology. Springer Berlin Heidelberg. Chapter 2.1</ref>:

'''Supporting Structures (Orbit, Extraoccular Muscles, Lacrimal Gland, Eyelid)'''
[[File:22292144 10208413540209536 722417340 o.jpg|250px|thumb|right| '''Figure 1.''' Layers of the Eyeball]]
The orbit consists of a framework of bones and connective tissue which provide structural support and protection to the sensitive human eye. 7 bones contribute to the orbit of the eye: frontal, lacrimal, sphenoid, zygomatic, ethmoid, maxillary, palatine. Several openings exist in the orbital structure, 2 key fissures are the superior orbital fissure and inferior orbital fissure and the posterior optic canal. These openings allow cranial nerves passageway.

A set of 6 extra-ocular muscles allow for a strong voluntary control of the movement of the eye. These muscles include the superior rectus, inferior rectus, lateral rectus, medial rectus, inferior oblique, superior oblique muscles. These muscles are some of the smallest in the human body and are able to produce fast, controlled motion to focus on an object of interest.

The eyelid is the anterior covering of the eye, consisting of a thin fold of skin. It is controlled by the levitator palpebrae superioris muscle. Supero-lateral to the eyelid is the lacrimal gland, which secretes a film of tear, an important component to keeping the anterior surface of the eye moist. The eyelid assists in this process by opening and closing, or blinking, which spreads the tear film across the surface of the eye. Debris caught in the tear film is excreted through the lacrimal duct which is located on the infero-medial surface of the eyelid.
[[File:22251179_10208414266827701_870733039_o.jpg|250px|thumb|right| '''Figure 2.''' Anterior Part of the Eye]]

'''Layers of the Eyeball (Sclera, Choroid, Retina)'''

The superficial layer of the eyeball is the sclera, a thick fibrous layer which thickens as it extends posteriorly. The sclera is visible as the white part of our eye. Its function is to provide structural stability to the eye and serves as attachment site for extra-ocular muscle insertions. Deep to the sclera is the choroid, a vascular network which provides nourishment to the layers of the eyeball and plays a large role in the growth of the eye. Deep to the choroid is the retina, a network of nerve fibres which transmit visual information. The retina contains 2 types of photoreceptors which convert visible light into nerve impulses (rods and cones). Rods work best in low light environments while cones work best in high light enthronements and detect colour and sharp detail.<ref>Curcio CA, Hendrickson AE. Organization and development of the primate photoreceptor mosaic. Prog Ret Ret. 1991;10:89–120.</ref>: The retina does not extend to the anterior part of the eyeball, unlike the sclera and choroid layers.

'''Anterior structure (Lens, Cornea, Pupil, Iris, Ciliary Body, Conjunctiva, Anterior Chamber)'''

The most anterior component of the eyeball is the cornea, which is a multilayered avascular transparent structure. Its major function is to refract incoming light to assist image formation on the retina (contributes about 75% of total refraction). Continuous with the cornea superiorly and inferiorly is the conjunctiva. Deep to the cornea is the iris, the pigmented ring of the eye. The iris consists of 2 muscles which act to enhance and diminish the size of the pupil (the aperture surrounded by the iris) allowing light to enter the eye. Deep to the pupil and iris is the lens, which is a transparent structure which contributes the other 25% of the eye's refractive power. The lens changes shape through accommodation (focusing) controlled by the ciliary body muscles, changing the position of images to form them on the retina. The ciliary body is the anterior extension of the choroid. Between the anterior surface of the lens and posterior surface of the cornea lies the anterior chamber. This chamber is filled with aqueous humour supplied by the ciliary body, which provides nutrients to ocular structures and maintains intra-ocular pressure.
[[File:22251314_10208414283908128_862494115_o.jpg|250px|thumb|right| '''Figure 3.''' Posterior Part of the Eye]]

'''Posterior structure (Optic Nerve, Optic Disc, Macula, Fovea, Posterior Chamber)'''

In the posterior section of the retina is the macula, a central spot in which a high concentration of cone photoreceptors are found. The direct centre of the macula is called the fovea which contains solely cone photoreceptors. The fovea is the only part of the eye which can conduct 'perfect' 20/20 vision. It has a high workload and hence a strong vascular supporting structure<ref><pubmed>6462623</pubmed></ref>:. The most posterior part of the eye is the optic nerve (along with the central retinal artery and central retinal vein), which is responsible for transporting nerve impulses to the cerebral cortex for processing. The opening of the optic nerve is called the optic disc, which contains no photoreceptors and is a blind spot of the eye. Between the posterior surface of the lens, the retina and the optic disc is the posterior chamber. The posterior chamber contains a vitreous humour, a jelly like substance with a high viscosity.

==Embryonic Contributions==

Eye development is a complex process. It involves the formation of the retina and the lens, which we together call the eyeball. It also involves the formation of auxiliary eye structures which are the eyelid, lacrimal gland, and cornea. The retina is formed from the neuroectoderm, the lens from the surface ectoderm and the auxiliary tissues are formed from the head surface ectoderm, neural crest cells and the head mesoderm <ref name="PMC3104407><pubmed>PMC3104407</pubmed></ref>.

[[File:Stage14 sem2cl.jpg|300px|thumb|right| '''Figure 4.''' Stage 14]]

{| class="wikitable"
! style="background:#f4a941" | Embryonic contributions
! style="background:#f4a941" | Eye component
|-
| Neuroectoderm of the forebrain || Retina, Posterior layers of the iris, The optic nerve
|-
| Surface ectoderm of the head || The lens of the eye, The corneal epithelium
|-
| Mesoderm between the neuroectoderm and the surface ectoderm || The fibrous and vascular coats of the eye
|-
| Neural crest cells || Choroid, Sclera, Corneal endothelium
|}

==Timeline of embryonic development==

{| class="wikitable"
! style="background:#f4a941" | WEEK
! style="background:#f4a941" | DEVELOPMENT
|-
| 3-4 || Eye fields, Optic vesicles
|-
| 5-6 || Optic Cup, Lens Vesicle, Choroid Fissure, Hyaloid Artery
|-
| 7-8 || Cornea, Anterior Chamber, Pupillary Membrane, Lens, Retina
|-
| 8-10 || Eyelids
|-
| 9-15 || Iris, Ciliary Body
|}

==Carnegie Stages==

Carnegie Stages are a system of 23 stages used to describe developmental events of the vertebrate embryo. At stage 10 we see early signs related to eye development. The table below is an made of knowledge from Anthony A. Person's article <ref><pubmed>7364662</pubmed></ref>.

{| class="pretty table"
|-bgcolor = "DDCEF2"
|'''Stage'''
|'''Events'''
|-bgcolor="FAF5FF"
|'''Stage 10 (22 days)'''
|The optic primordium has developed. Two small grooves develop on each side of the developing forebrain in the neural folds - this is the optic grooves. The optic placode has begun to develop, which is seen by a small thickening of the surface ectoderm lateral to the hindbrain.
|-
|'''Stage 11 (24 days)'''
|Optic vesicle begins to form from the optic groove.

[[File:Stage11 histology-optic pit.jpg|300px|'''Figure 1.''' Stage 11]]
|-bgcolor="FAF5FF"
|'''Stage 12 (26 days)'''
|The optic vesicles have extended from the forbrain to the surface ectoderm. The optic vesicle now lies close to the surface ectoderm.
|-
|'''Stage 13 (28 days)'''
| The optic vesicle interacts with the surface ectoderm and will induce this ectoderm to form the lens placode, which is the precursor of the lens. Optic evagination differentiation makes it possible to identiy optic parts of retina, future pigmented layer of retina and optic stalk.

[[File:Stage_13_image_060.jpg|300px|'''Figure 2.''' Stage 13]]
|-bgcolor="FAF5FF"
|'''Stage 14 (32 days)'''
| The lens placode is indented by the lens pit and is cup-shaped.
|-
| '''Stage 15 (33 days)'''
| The lens pit will close and form a circle that separates from the surface ectoderm and becomes the lens vesicle. The lens vesicle and optic cub lie close to the surface ectoderm, which creates a slight elevation in the region of the eye.
|-bgcolor="FAF5FF"
| '''Stage 16 (37 days )'''
| The lens body has grown and now has a D-shaped lens cavity. First indication of the development of the eyelids visible as eyelid grooves above and below the eye.
|-
| '''Stage 17 - 19'''
| Retinal pigment is visible and the retinal fissure is almost closed. The eyes are still laterally placed but starts to take a more anterior position. The lower eyelid fold develops first and then the eyelid fold above the eye.
|-bgcolor="FAF5FF"
| '''Stage 18 (44 days)'''
| Mesenchyme invades the region between the lens epithelium and the surface ectoderm. The eyes have shifted to a more anterior position. The groove above and below the eyes are deeper but have not joined yet.
|-
| '''Stage 19 - 22'''
| The eyelid folds develop into the eyelids and the upper and the lower eyelids now meet at the outer canthus, which is the corner of the eye.

[[File:Stage 22 image 208.jpg|300px|'''Figure 3.''' Stage 22]]
|-bgcolor="FAF5FF"
| '''Stage 20 (51 days)'''
| The lens cavity is lost. The upper and lower lids meet laterally and medially. The eyelids now partly cover the eye. Lens suture begins to form.
|-
| '''Stage 23 (57 days)'''
| End of embryonic period. The face begins to look human. Eyelids closure is complete.
|-
|-bgcolor="FAF5FF"
|-
|}

==Development of the eye components==

===Introduction===

<html5media width=“480" height="360">https://www.youtube.com/embed/ghHDFWlfpoQ</html5media>

[[File:DevelopmentEye-PMC43029243.jpg|400px|thumb|right|'''Figure 5.''' Stages of lens formation in mouse embryos]]

The eye starts to develop at 22 days. The optic grooves (sulci) appears in the neural folds at the cranial end of the embryo. When the neural fold fuse to form the forebrain, the optic grooves will form '''optic vesicles'''. The optic vesicles are continuous cavities from the cavity of the forebrain and project from the wall of the forebrain and into the mesenchyme. The optic vesicle extends from the diencephalon and will come in contact with the surface ectoderm of the head. This induces the formation of a lens placode <ref name="Larsen'sHumanEmbryology">Schoenwolf, G.C., Bleyl, S.B., Brauer, P.R., Francis-West, P.H. & Philippa H. (2015). Larsen's human embryology (5th ed.). New York; Edinburgh: Churchill Livingstone.</ref>.

The surface ectoderm near the optic vesicles will thicken and form the '''lens placodes'''. The lens placodes will sink into the surface ectoderm and form '''lens pits'''. The edges of the lens pits will travel towards each other and fuse to form round '''lens vesicles''', which will later lose connection with the surface ectoderm. The optic vesicles do also keep developing - they will form double-walled '''optic cups''' which are connected to the brain by the '''optic stalk'''. The two layers of the optic cup will differentiate in different directions. The cells of the outer layer will produce melanin pigment and later become the '''pigmented retina'''. The cells of the inner layer of the optic cup will proliferate fast and develop glia, ganglion cells, interneurons and light-sensitive photoreceptor neurons. These cells are in the '''neural retina'''. The ganglion cells of the retina are neurons that send signals to the brain. The axons of the ganglion cells of the neural retina will grow in the wall of the optic stalk. The cavity in the optic nerve will start disappearing, and instead, the axons of the ganglion cells will form the '''optic nerve'''. The optic stalk is now the optic nerve <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>

The optic cups will fold inwards around the lens while the lens vesicles have grown inwards so they have fully lost their connection with the surface ectoderm, which locates them in the cavities of the optic cups. The retinal fissures (linear grooves) will develop and cover the ventral surface of the optic cups and down to the optic stalk. The retinal fissures contain vascular mesenchyme and hyaloid blood vessels will develop here. The hyaloid artery supplies the structures in the eye with blood and the hyaloid vein will return the blood from these structures <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

'''Formation of the optic vesicle'''

It is a specific area of the neural ectoderm that will become the optic vesicle - this happens because of a group of transcription factors - Six3, Pax6, and Rx1. These transcription factors are expressed in the most anterior tip of the neural plate. This area will split into bilateral regions and form the optic vesicles. The Pax6 protein has shown to be especially important for the development of the lens and retina. This protein is important for photoreceptive cells in all phyla. Pax 6 is also present in the murine forebrain, hindbrain, and nasal placodes, but the eyes are most sensitive its absence <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

The sonic hedgehog gene is important for the separation of the single eye field into two fields. If this gene is inhibited, the eye field will not split which will result in cyclopia, a single eye in the center of the face <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

===Retina===

[[File:Bailey463.jpg|400px|thumb|right|'''Figure 6.''' Diagram of developing lens and optic cup]]

The retina is the essential component of the eye with the primary function of photoreception <ref><pubmed>7084144</pubmed></ref>. Formation of the retina begins with the specification of retinal cells in the anterior neuroectoderm. First morphological sign of eye development is the formation of two lateral grooves in the anterior neuroectoderm, which is called the optic sulci. The cells of the optic sulci will evaginate and form the optic vesicle. The distal portion of the optic vesicle will form the retina and the proximal will form the optic stalk <ref><pubmed>18675797 </pubmed></ref>. The retina develops from the walls of the optic cup, these walls develop into the two layers of the retina. The thin, outer layer of the optic cup will become the pigment layer of the retina and the thick, inner layer of the optic cup will differentiate into the neural retina. Forkhead transcription factors are regulating the proliferation and differentiation of the retinal precursor cells. During the embryonic and early fetal periods, the two layers of the retina are separated which makes an intraretinal space. The intraretinal space is derived from the cavity of the optic cup. The two layers of the retina will fuse and the intraretinal space will gradually disappear <ref name="Larsen'sHumanEmbryology">Schoenwolf, G.C., Bleyl, S.B., Brauer, P.R., Francis-West, P.H. & Philippa H. (2015). Larsen's human embryology (5th ed.). New York; Edinburgh: Churchill Livingstone.</ref>.

When the lens is developing the inner layer of the optic cup starts to proliferate and forms a thick neuroepithelium which will later differentiate into the neural retina. The neural retina contains photoreceptors and the cell bodies of neurons and is the light-sensitive region of the retina. The axons of the ganglion cells in the neural retina grow in the wall of the optic stalk and will form the optic nerve <ref name="Larsen'sHumanEmbryology">Schoenwolf, G.C., Bleyl, S.B., Brauer, P.R., Francis-West, P.H. & Philippa H. (2015). Larsen's human embryology (5th ed.). New York; Edinburgh: Churchill Livingstone.</ref>.

===Lens===

Human lens induction occurs at around 28 days and is completed around day 56. The surface ectoderm will thicken near the optic vesicle and create the lens placode and later form the lens vesicle <ref><pubmed>20171212 </pubmed></ref>. Lens cells come from ectoderm and differentiate into either lens fibers or the lens epithelium. The anterior monolayer of epithelial cells of the lens will create the lens epithelium, which makes the sheet of cuboidal epithelium covering the anterior surface of the lens. The posterior lens vesicle cells will produce the linear primary fibre cells aligned parallel to the optic axis. These fibres will create the lens mass and form the embryonic lens nucleus. The lens epithelial cells will keep proliferating and produce new cells which generate a secondary lens fiber cells. This rows of cell will form the outer shells and keep the lens growing throughout life. This makes the eye lens unique - it will have an addition of new cells inside the surrounding capsule all the time <ref><pubmed>25406393</pubmed></ref>.

===Ciliary Body===

The ciliary body is a muscular and secretory tissue and is located directly behind the lens. The ciliary body forms part of the anterior segment of the eye and is an important regulator of eye physiology and the vision. The ciliary body produces the aqueous fluid which fills the eyes and nourishes the lens and cornea - this aqueous fluid function to keep the eye in a pressurized and inflated state, which is important the vision.The ciliary body also synthesizes collagenIX and tenasin-C <ref><pubmed>17275804</pubmed></ref>.

The ciliary body extends from the iris root (anteriorly) to the ora serrata (posteriorly). It consist of ciliary muscles and ciliary processes. Each ciliary process (fold) is covered by a double-layered secretory epithelium; the outer pigmented and the inner unpigmented (closes to the lens). The epithelial layers of the ciliary body comes from the retina of the optic cup. We see two different ciliary body epithelium: the inner non-pigmented ciliary epithelium which is connected with the neural retina and the outer pigmented ciliary epithelium which is connected with the retinal pigmented epithelium. The epithelium of the iris is the further anterior extension. The epithelial layers are associated with a stroma containing the ciliary muscle. The ciliary muscle is complex, but can be divided into three portions; anterior, posterior and internal <ref><pubmed>12127103</pubmed></ref>.

In the chick eye development, we see the mesenchyme grow together on the margin of the optic cup and will form the stroma of the ciliary body and the iris, which is located more anteriorly. It is unknown how if the lens has a role in inducing the secretory ciliary body epithelium and the muscular iris epithelium <ref><pubmed>17275804</pubmed></ref>.

===Iris===

The iris is the circular, pigmented muscular portion of the eye with a central aperture that is the pupil. The main function of this round muscle is to manipulate pupil diameter as an adjustment to various conditions and to control the amount of light entering the eye <ref name=’’21413392’’><pubmed>21413392</pubmed></ref>. This is influenced by dilator pupillae (radial) and sphincter pupillae (constricting) muscles. Iris pigmentation is dependent on the abundance and distribution of certain types of melanin in the posterior epithelium of the iris (eumelanin and pheomelanin) <ref name=’’21413392’’/>.

The Iris develops at the end of the third month of development. The iris is a thin layer and derives from the anterior rim of the optic cup <ref><pubmed>22219630</pubmed></ref>. The iris is formed by the pigment-containing internal and external layers of the optic cup and by a layer of vascularised connective tissue which also contains the pupillary muscles. Internal layers of the optic cup form the non-pigmented iris parts whereas the external layers of the optic cup develop into the pigmented epithelial structures. <ref name=’’18168498’’><pubmed>18168498</pubmed></ref>. Iris stroma develops as a result of neural crest cell migration – within this stroma, the dilator and constrictor muscles develop from the neuroectoderm of the optic cup. In the anterior of the eye, the optic epithelium is non-neural and matures as ciliary body and iris epithelia <ref name=’’18168498’’/>.

===Cornea===

The cornea is the unique, transparent and avascular component located at the most anterior section of the eye. It is composed of five layers stemming from the 3 main layers of epithelium, stroma and endothelium:

* Corneal epithelium (most anteriorly) – consisting of multiple layers of cells which rest on a basement membrane.
* Bowman’s membrane – a clear, acellular homogenous layer. This layer is a modified portion of the stroma and has no regenerative capacity as a response to damage <ref name=''7084144''><pubmed>7084144</pubmed></ref>.
* Corneal stroma – largest portion of the retina consisting of collagenous tissue.
* Descemet’s membrane – a homogenous, elastic true basement layer with a regenerative capacity.
* Corneal endothelium – a single layer of cuboidal cells responsible for the maintenance of the dehydrative nature of corneal tissue. <ref name=''7084144''/>.

Corneal development involves interactions between ectoderm-derived tissues. More specifically, the corneal epithelium arises from interactions between the cranial ectoderm and optic vesicles derived from the neural ectoderm <ref name=''26310148''><pubmed>26310148</ref></pubmed>. The neural tube and the adjacent ectoderm give rise to the neural crest cells which are multipotent with a migratory capacity. These cells contribute to the formation of corneal epithelium and the stromal cells. Innervation of the cornea stroma and epithelium is derived from both the neural crest and the ectodermal placode <ref name=''26310148''/>. The endothelium is comprised of differentiated neural crest cells which contribute to the later formation of Descemet’s membrane <ref><pubmed>6511224</pubmed></ref>.

===Aqueous Chambers===

There are two aqueous chambers of the eye: anterior and poster. These chambers are filled with a plasma-like fluid called aqueous humour and is produced by the ciliary body and trabecular meshwork in 3 main stages: diffusion, ultrafiltration and active secretion <ref><pubmed>6763801</pubmed></ref>. The main function of this fluid is to maintain the intraocular pressure as well as provide structural integrity to the round shape of the eyeball. This structure also has a role in the immune response and provides nutrition to the avascular tissue (e.g., the cornea and lens). <ref><pubmed>21293732</pubmed></ref>.

The anterior chamber is defined as the developed space posterior to the cornea (between the cornea and the iris) and develops at the stage of differentiation of the mesodermal portion of the iris <ref name=’’18168498’’/>. The space defining the posterior chamber develops as the mesenchyme between the lens and the peripheral iris.

===Choroid and Sclera===

The choroid and sclera are both surround the eye and are located adjacent to each other (the choroid lines the inner portion of the sclera). The sclera is the outer, fibrous white layer of the eye which functions as a supportive wall of the eye ball and is continuous with the cornea <ref name=''7084144''/> . The heavy vasculature of the choroid provides a major supply of oxygen and nourishment to the retina <ref><pubmed>20044062</pubmed></ref>.
They are derived from interactions between the neural crest and mesoderm-derived mesenchyme. The sclera forms as a result of condensation of the mesenchyme outside the optic cup <ref><pubmed>1628748</pubmed></ref>.
The choroid arises from the mesenchyme surrounding the optic vesicle and the cranial neural crest cells. The first vasculature structures appear in the choroid during week 15 in the form of arterioles and venules; veins and arteries become distinguishable by week 22 <ref name=’’2199235’’><pubmed>2199235</pubmed></ref>.

===Extraocular muscles===

The extraocular muscles are responsible for eye movement within the eye orbit – a critical aspect of sight and communication. 6 main muscles contribute to eye movement. These include: superior rectus, inferior rectus, lateral rectus, medial rectus, superior oblique and inferior oblique.

The development of these muscles is dependent on interactions between the eye, its muscles and the neural crest. <ref name=''21482859''><pubmed>21482859</pubmed></ref>.
Somites supplied by cranial nerve III forms 5 of the 6 extraocular muscles which form an interlocking tendinous ring made of fibrous connective tissue. The 5 muscles include the lateral, medial, superior and inferior rectus, and the superior oblique muscle. This common tendinous ring is known as the annulus of Zinn and surrounds the entry of the optic nerve. The remaining sixth muscle is the inferior oblique muscle and is separate from the aforementioned tendinous ring due to its distinct point of origin. <ref name=''21482859''/>.

===Eyelids===

The eyelids are upper and lower folds of skin functioning as a barrier protecting the anterior surface of the eye from direct local injury. Eyelids also regulate light exposure, distribute precorneal tear film over the corneal surface when blinking and are involved in functions involving tear flow <ref><pubmed>1993591</pubmed></ref>.
No sign of eyelid fold development is evident at week 5 however at this stage the lens pit begins to invaginate from the surface ectoderm <ref name=’’27124372’’><pubmed>27124372</pubmed></ref>. Week 6 initiates the timeline of eyelid development as small depressions emerge in the surface ectoderm both above and below the developing eye – these rapidly deepen to form the folds of the eyelids <ref name=‘’7364662’’><pubmed>7364662</pubmed></ref>. The lower eyelid fold develops first and, by the end of week 6, the lower fold is more distinct than the upper eyelid fold <ref><pubmed>21416630</pubmed></ref>. Week 7 marks the point at which both the upper and lower folds are distinctly developed and during this stage, the upper lid assumes its more dominant role <ref name=’’27124372’’/>. The eyelid is not fully closed - there is a gap between the folds and the cornea is slightly visible – they eventually undergo fusion in week 8 <ref name=’’27124372’’/>.

===Lacrimal Glands===

The lacrimal glands are exocrine glands located in the upper lateral region of each eye orbit which secrete the aqueous potion of the tear film. This film is continuously secreted and functions to clean and protect the external surface of the eye, keeping the environment constantly moist and preventing possible injury from dust and other particles <ref><pubmed>17001201</ref>.
Lacrimal gland morphogenesis is identified in three stages.

* The first is the presumptive glandular stage. This stage involves the thickening of the conjunctival superior fornix epithelium and the condensing of the surrounding mesenchyme <ref name=’’14635806’’><pubmed>14635806</pubmed></ref>.

* The second is the bud stage. This stage is considered the initial sign of glandular formation due to the development of nodular structures and lumina within epithelia buds <ref name=’’14635806’’/>.

* The third is the glandular maturity stage (week 9-16). In this stage, the lacrimal gland begins to morphologically mirror the adult gland <ref name=’’14635806’’/>.

==Signalling pathways and transcription factors involved throughout eye development==

===Eye field development===

Many signalling pathways and transcription factors are involved in the development of the eye field (which forms in addition to the telencephalon and diencephalon as part of division of the anterior neural plate). Eye progenitor cells are guided into the eye field region by fibroblast growth factor, bone morphogenetic protein and Wnt-signalling pathways <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>. Additionally, interactions between canonical and non-canonical Wnt-signalling have been shown to maintain the eye field border <ref name=’’16413771’><pubmed>16413771</pubmed></ref>.

The cells of the eye field express eye field transcription factors, some of which include Rx1/Rax, Pax6, Lhx2, Six3 and Otx2. Six3, Pax6, Otx2 and Rx1 specify retinal lineage and regulate progenitor cell movement to guide them to their correct locations <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>. Six3 also partly mediates Wnt-signalling repression, allowing for the development of the optic vesicles from the eye field <ref name=’’23684892 ’’><pubmed>23684892 </pubmed></ref>. Lhx2 maintains optic lineage in eye progenitor cells and suppresses the potential for differentiation towards different fates <ref name=’’23595746’’><pubmed>23595746</pubmed></ref>.

===Eye field division and progression to optic cup===

TGF-β, FGF and Shh family factors secreted by the axial mesoderm underlying the eye field initiate its splitting into two bilateral, symmetric eye primordia <ref name=’’23684892 ’’><pubmed>23684892 </pubmed></ref>. These factors also regulate the expression of transcription factors Pax2, Pax6, Vax1 and Vax2, thereby establishing the boundaries and patterning the proxiodistal and ventronasal axes of the optic vesicles <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>.

Despite the close relationship between cellular proliferation and morphogenesis, optic vesicle evagination does not appear to be mainly driven by proliferation <ref name=’’23684892 ’’><pubmed>23684892 </pubmed></ref>. Alternatively, it has been shown that retinoic acid has critical importance in optic vesicle evagination to form the optic cup <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>. Rx3 activity has also been observed to have involvement in optic vesicle evagination <ref name=’’23684892 ’’><pubmed>23684892 </pubmed></ref>.

===From optic cup to developed eye===

Lens placode maturation and lens development is dependent on Pax6 expression and regulation. During placode formation bone morphogenetic protein and fibroblast growth factor signalling regulate Pax6. Within the presumptive lens ectoderm, Pax6 is regulated by Six3 and Meis. However, within the presumptive epithelium Pax6 is a regulating factor, regulating the expression of Sox2 and eventually Six3 once the lens placode is formed <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>.

Meanwhile, in the primordial retina retinal progenitor cells become retinal ganglion cells through the expression of the basic helix-loop-helix transcription factor ath5 (which is regulated by Hh and Fgf signalling. The amacrine, horizontal and bipolar cells of the retina are generated by a variety of transcription factors, some of which include Pax6, Six3 and Foxn4 <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>. Crx and Otx2 positive cells progress towards photoreceptor fates and are further developed into rods and cones based on specific transcription factor expression (TRβ2 and RxRγ expression is required for cones, where as Nrl, Nr2e3 and Ascl1 expression is required for rods) <ref name=’’20648062’’><pubmed>20648062</pubmed></ref>. The transcription factors required for the development of the retinal pigment epithelium include Mitf, Otx1/Otx2 and Pax6. TGF-β, FGF, BMP and Hh signalling from the surrounding mesenchyme have also been shown to help induce retinal pigment epithelium fate in progenitor cells <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>.

Within the choroid, the expression and regulation of many different factors and signalling pathways is required for the development of proper arterial-venous connections, allowing for the functional circulation of nutrients and oxygen throughout the eye. VEGF, bFGF, PDGF and PEDF (from the retinal pigment epithelium) drive the development and maturation of choroidal blood vessels. Vascular patterning is regulated by the interactions between VEGF and Delta-like 4 factors. Additionally, Notch signalling has been shown to have importance in the formation of capillary beds <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>.

===Eye formation in the absence of the retina===

The gene Rx is a key component in the formation of retinal structures. Studies have shown that mice lacking Rx function do not form optic sulci or optic vesicles and do not have retina-specific gene expression. There has been made studies in human, medaka, zebrafish and Xenopus which suggest that Rx genes are required for the formation of the vertebrate retina. It is also shown that in Rx-deficient mouse embryos the mature lens does not develop. This indicates that retinal cells are necessary for lens formation, and if the mouse is lacking Rx gene, then it will not display any retina-specific gene expression <ref name="PMC3104407"/>.

It is thought that signaling from the optic vesicle is important to activate the lens-specific gene and the formation of the lens placode. If there are no retinal cells generated, then the morphogenesis of the optic cup does not take place and the lens will not form. The study also showed that elimination of β-catenin expression in the head surface ectoderm in Rx-deficient embryos would develop a lens-like structure even though there were no optic vesicle/cup. Elimination of β-catenin lead to upregulation of Pax6, which is a gene that has a key role in lens formation. This indicates that the optic vesicle/cup might not be required for lens formation. The lens developed smaller than in wild type embryos, which means that the optic cup/vesicle might have an effect on a determination of the size of the lens. It could be that the developing optic vesicle/cup shields the developing lens placode from signals for other tissues that could disturb the lens formation <ref name="PMC3104407"/>.

It is not fully understood if the formation of the auxiliary eye structures is dependent on the development of the eyeball and its components, the retina and the lens. A study made my Eric C. Swindell and al. showed that auxiliary eye structures form even in the absence of retinal morphogenesis and retina-specific gene expression. This indicates that there are two separate developmental processes involved in the formation of the eye and its associated structures. In the absence of the retina and the lens, we still see specific gene expression in the surface ectoderm initiating the formation of auxiliary eye structures like eyelids and lacrimal glands <ref name="PMC3104407"/>.

==Current research==

===Iris epithelium cells as a potential source for regenerative medicine for retinal pigment epithelium degeneration===

The retinal pigment epithelium (RPE) is a monolayer of neural-crest-derived cells and is located between the photoreceptors and the choroid. There are many disorders that involve dysfunctional RPE and leads to retinal degenerative diseases. There is no treatment for these diseases, therefore, one of the most promising future therapy for RPE related disorders is to replace the cells of the dysfunctional RPE <ref name="PMC5565104><pubmed>PMC5565104</pubmed></ref>..

Studies have focused on the development and use of induced pluripotent stem cells (iPSC) for cell replacement therapy. It is possible to differentiate iPSC in vitro towards RPE cells and use them for experimental transplantation studies in animal models. But an alternative strategy for a retinal replacement is based on transdifferentiation (direct conversion) and involves transforming an adult somatic cell into another adult somatic cell. Use of overexpression of cell-lineage specific genes can convert one cell into another cell type and skip the pluripotent state. Iris epithelium (IE) cells might be able to be transdifferentiated into the RPE since both RPE and IE are neuro-epithelia and has a common embryological origin - they both derive from neuroectoderm of the developing optic cup <ref name="PMC5565104"/>.

A study made by Anna Bennis et al. <ref name="PMC5565104"/>. has shown that the canonical pathways for the most highly expressed genes of the IE and the RPE were very similar. Wnt signaling pathways has shown to be active in the IE but not in the RPE. The Wnt signaling pathway consists of a group of signal transduction pathways that has an influence on cell fate determination and cell proliferation during embryonic development. Activation of Wnt SP makes it possible to reprogram somatic cells (also retinal neurons) into iPSC and is important for the differentiation of pluripotent stem cells to RPE cells. The high expression of Wnt SP genes in the iE suggests that the IE has a multipotent character during life and therefore could be transformed into RPE cells used for RPE replacement <ref name="PMC5565104"/>.

===UNSW Optometry and Vision Science Current Projects===

Additionally, UNSW has a number of current research projects currently being undertaken <ref>https://www.optometry.unsw.edu.au/research/current-research</ref>

A few interesting topics include:
- Biochemical changes in the tear film in relationship to the corneal structural changes in diabetes so as to be able to predict nerve damage earlier
- The use of video games and virtual reality (visual electrophysiology) to help treat some congenital anomalies such as lazy eye
- How retinal circuitry operates with regards to neurotransmitter release, receptor location and receptor function, allowing the development of a retinal roadmap which can be applied to retinal diseases

==Animal Models==
The zebrafish species is used to investigate ocular development, function and disease due to having the same morphology as other vertebrates including humans. The advantages of zebrafish include: they are able to quickly reach their sexual maturity, they behaviour can be observed quite early on because of their rapid development and most importantly, their embryos are translucent. Zebrafish is also active during the day therefore their retina contains a large number of diverse cone subtypes in additions to rods. <ref name="Zebrafish"> Glass, A. S. & Dahm, R. (2003). The Zebrafish as a Model Organism for Eye Development. ''Opthalmic Research, 36''(1), 4-24. doi: 10.1159/000076105</ref>

[[File:Chokh.png|250px|thumb|left| '''Figure 11.''' Wild type zebrafish vs chokh/rx3 knockout. Morphological differences with the absence of eyes in the knockout.]]
Through studying zebrafish, it was found that that a mutation in ''chokh/rx3'' gene results in the absence of eyes during the earliest stages of development due to failure of the retinal progenitor cells. <ref name="chokh">Loosli, F., Staub, W., Finger-Baier, K. C., Ober, E. A., Verkade, H., Wittbrodt, J. & Baier, H. (2003). Loss of eyes in zebrafish caused by mutation of chokh/rx3. ''EMBO Reports, 4''(9), 894-899. doi: 10.1038/sj.embor.embor919 </ref>. Optical vesicle is turned inside out and the neuronal differentiation is blocked. In this study, they have found that the DNA-binding homeodomain and the the entire C-terminal portion led to a nonsense mutation that resulted to complete loss of function in the eye. It was concluded that the gene ''chokh/rx3'' is important for the developing optic primordia.

==Congenital Abnormalities==
Although quite rare, abnormalities can occur during the embryonic development that causes serious effects to the features of the eyes, its function as well as the further normal development after birth. These abnormalities can occur unilaterally or bilaterally and it is also common for most reported cases to have more than one type of eye abnormalities at a time. Thus, the estimated prevalence statistics listed in the table can overlap.

{| class="wikitable"
! style="background:#f4a941" | Congenital Anomalies
! style="background:#f4a941" | Description
! style="background:#f4a941" | Epidemiology
|-
| Anopthalmia || The absence of the eyes.
| rowspan="2" | Prevalence: Anophthalmia-Microphthalmia Syndrome was estimated to be 5.3 per 100 000 cases <ref name="Anophthalmia">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: [[http://www.orpha.net/consor/cgi-bin/index.php]] </ref>
Cause: SOX2 gene mutation <ref name="SOX2 Gene"> Mauri, L., Franzoni, A., Scarcello, M.,
Sala, S., Garavelli, L. Modugno, A., ... Penco, S. (2015). SOX2, OTX2 and PAX6 analysis in subjects with anophthalmia and microphthalmia. ''European Journal of Medical Genetics, 58'', 66-70. doi: 10.1016/j.ejmg.2014.12.005 </ref>
|-
| Microphtalmia || Abnormal reduction in size of the eyeballs.
|-
| Keratoglobus || Structural abnormalities in the formation of the cornea - unknown cause - fixable through surgery<ref name="PMID23807384"><pubmed>23807384</pubmed></ref>
| Prevalence: understood to be a rare condition<ref name="PMID23807384"><pubmed>23807384</pubmed></ref>
|-
| Ptosis ('Lazy Eye')|| Structural abnormalities in the eyelid, can be congenital - specifically the failure of innervation of the oculomotor nerve for levator palpebrae superioris <ref name="PMID8759493"><pubmed>8759493</pubmed></ref> - fixable through surgery
| Prevalence: a relatively well known abnormality
|-
| Aphakia || Te absense of a lens in the eye, causing a loss of accommodation and hence far-sightedness. People with aphakia have relatively small pupils which are unable to dilate as much <ref name="PMID28913511"><pubmed>28913511</pubmed></ref>
| Prevalence: a rare congenital abnormality
|-
| Coloboma || A condition where parts of the eye is missing and failed to develop normally.
| Prevalence: Occular coloboma was estimated to be 8.0 per 100 000 cases <ref name="Anophthalmia">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: [[http://www.orpha.net/consor/cgi-bin/index.php]] </ref>
|-
| Aniridia || Complete or partial absence of the iris.
| Prevalence: Estimated to be 1.5 per 100 000 cases <ref name="Anophthalmia">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: [[http://www.orpha.net/consor/cgi-bin/index.php]] </ref>
|-
| Optic Nerve Hypoplasia || A condition where the optic nerves are underdeveloped.
| Prevalence: Reported to be the most common abnormality <ref name="The Optic Nerve Hypoplasia">Ryabets-Lienhard, A., Stewart, C., Borchert, M., & Geffner, M. E. (2016). The Optic Nerve Hypoplasia Spectrum - Review of the Literature and Clinical Guidelines. ''Advances in Pediatrics, 63'', 127-146. doi: 10.1016/j.yapd.2016.04.009 </ref>
*10.9 per 100 000 in United Kingdom
*17.3 per 100 000 cases in Sweden.
*6.3% of cases was reported in New Zealand
|-
|}

<gallery>

Anophthalmia.jpeg|'''Figure 8.''' Anopthalmia
Microphthalmia-500px.jpg| '''Figure 9.''' Microphthalmia
Opac_figure_7.jpg| '''Figure 10.''' Iris Coloboma
Opac figure 10.jpg| '''Figure 11.''' Partial Aniridia
</gallery>

==Future questions==
===Will it be possible to have eye transplants in the future?===
Lots of research has been done in making a whole-eye transplantation successful in order to finally cure blindness. Blindness is a worldwide problem and is currently untreatable due to the fact that retinal ganglion cells and the optic nerves do not regenerate. This can result from diseases including macular degeneration and end of stage glaucoma. The first successful eye transplantation was led by Stone and Cole in 1943<ref name="Return of Vision"> Stone, L. S. & Cole, C. H. (1943). Grafted Eyes of Young and Old Adult Salamanders (Amblystoma Punctatum) Showing Return of Vision. ''Yale Journal of Biology and Medicine, 15''(5), 735-754.2. PMCID: PMC2601300</ref> investigating 104 samples of the salamander species, ''Amblystoma Punctatum'', and one of its eyes were either implanted back into the same animal or it was completely transplanted to a new host. It was reported that circulation in the iris was re-established, retina was able to regenerate, a new optic nerve was connected to the brain through the optic chiasma and ocular movements were regained. Vision was reestablished by the second month. In a more recent study, in 2015, Li et al.<ref name="Structural Integrity"> Li, Y., Komatsu, C., Wang, B., Miller, M., Wang, H., van der Merwe, Y., Ho, L., Kostereva, N., Zhang, W., Xiao, B., Davidson, E., Solari, M., Steketee, M. B., Guo, S., Kagemann, L., Wollstein, G., Schuman, J., Chan, K., Gorantla, V. S., Washington, K. M. (2015). Abstract 112: Evaluation of Viability, Structural Integrity and Functional Outcome after Whole Eye Transplantation. ''Plastic & Reconstructive Surgery, 135''(5), 82. "PMC2601300"</ref> investigated the feasibility of eye transplantation by observing the surviving 15 rat models out of the original 22. They were able to confirm the integrity and functional return of vision after whole-eye surgeries with the aid of advance techniques that are available today. The Ear and Eye Foundation of Pittsburgh<ref>'''Ear and Eye Foundation of Pittsburgh''': https://eyeandear.org/our-research/ophthalmology/the-whole-eye-transplant-project</ref> is an organization that is currently running a project with lead researchers to discover a way for the optic nerves to regenerate and to cure blindness by 2020.

===Will the bionic eye pass clinical trials in the next few years?===
[[File:BionicEye.jpg|250px|thumb|left| '''Figure 12.''' Bionic Eye Diagram]]

The bionic eye is an external visual device that has been in the making for the last several years. It hopes to bring back full vision through the aid of a pair of glasses with a camera attached to it, which then transmits high-frequency radio signals to the microchip implanted in the users' eye. These signals are converted into electrical impulses by the electrodes implanted in the chip, which then stimulates the retinal cells and passes through the optic nerve. Electrical impulses travels to the vision processing centres in the brain and these are then interpreted as an image. At the moment, users must learn to understand light flashes and visual patterns and convert them into images they can interpret. Current prototypes require the users to have a previously working eyes, which means their optic nerves must still be relatively healthy and their visual cortex must be developed. Patients who have suffered from retinitis pigmentosa and age-related macular degeneration would benefit this technology. Bionic Vision Australia<ref>'''Bionic Vision Australia''': http://bionicvision.org.au/about/research_plan</ref> is one of the leading organisations that are aiming to treat blindness and are set to perform clinical trials on two of the devices of the bionic eye implants soon. Their objectives are to develop strategies that can improve the affected visual pathway to the brain by stimulating the remaining working retinal cells and also develop safe surgical procedures.

==Glossary==

{| class="pretty table"
|-bgcolor = "DDCEF2"
|'''Term'''
|'''Definition'''
|-bgcolor="FAF5FF"
|'''Age-related macular degeneration'''||An eye disease with its onset usually after age 60 that can progressively destroy the macula, the central portion of the retina, impairing central vision.
|-
|'''Aqueous humour'''||A transparent fluid similar to plasma with low protein concentrations secreted by the ciliary epithelium.
|-
|'''Choroid'''||The pigmented vascular layer of the eye located between the retina and sclera.
|-
|'''Choroid fissure'''||A ventral groove formed by the invagination of the optic cup located at the bottom of the optic vesicle through which blood vessels enter the eye.
|-
|'''Ciliary body'''||The connection between the iris and choroid consisting of the ciliary muscle, ciliary processes and the ciliary ring. Alters the shape of the lens and ciliary epithelium in order to focus on an image.
|-
|'''Cornea'''||The transparent anterior part of the external coat of the eye covering the iris and pupil and continuous with the sclera.
|-
|'''Ectoderm||The outermost primary germ cell layer in the early embryo.
|-
|'''Endoderm||The innermost primary germ cell layer in the early embryo.
|-
|'''Ectodermal placode'''||A neurogenic placode consisting of an area of thickened epithelium in the embryonic head ectoderm layer that gives rise to neurons and other structures of the sensory system.
|-
|'''Extraocular muscles'''||Muscles controlling eye movement.
|-
|'''Fovea'''||A small depression in the retina where visual acuity is the highest.
|-
|'''Hyaloid vasculature'''||The temporary circulatory system in fetal eyes which spontaneously degenerate when the retinal blood vessels begin to develop.
|-
|'''Intraocular pressure'''||Fluid pressure inside the eye created through continued renewal of fluids.
|-
|'''Iris'''||The coloured muscular ring surrounding the pupil which manipulates the diameter and size of the pupil and controls the amount of light entering the eye.
|-
|'''Lens'''||The transparent biconvex structure posterior to the iris with the main function of focusing light onto the retina in order to form clear images of objects at various distances.
|-
|'''Lens pit'''||A pit-like depression in the fetal head where the lens develops.
|-
|'''Lens placode'''||The placode developing in the ectoderm overlying the optic vesicle, eventually becoming the lens of the eye.
|-
|'''Lens vesicle'''||The ectodermal invagination in the embryo formed opposite the optic cup and gives rise to the lens.
|-
|'''Lumina'''||the central cavity of a tubular structure.
|-
|'''Macula'''||An oval-shaped pigmented area where there is the largest density of cone cells and is involved in producing the sharpness of central vision.
|-
|'''Mesenchyme'''||Loosely organised embryonic connective tissue originating from the mesoderm.
|-
|'''Neural crest'''||A temporary group of embryonic ectodermal cells.
|-
|'''Neural retina'''||Refers to three layers of neural cells within the retina (photoreceptor cells, bipolar cells and ganglion cells).
|-
|'''Neural tube'''||A hollow tubular structure as a result of neural plate folding which later develops into the brain and spinal cord.
|-
|'''Neuroepithelium'''||Epithelium consisting of specialised cells which detect sensory triggers for reception of external stimuli.
|-
|'''Optic cup'''||A structure of the diencephalon formed after optic vesicle folding. This structure gives rise to the retina.
|-
|'''Optic groove'''||Two small grooves on each side of the developing forebrain in the neural folds. Also chiasmatic groove.
|-
|'''Optic nerve'''||Cranial nerve II which transmits impulses to the brain from visual information detected by the photoreceptive retina.
|-
|'''Optic stalk'''||Pair of slender embryonic structures that give rise to the optic nerve.
|-
|'''Optic vesicle'''||An evagination of each lateral all of the embryonic vertebrate forebrain from which the nervous structures of the eye develop.
|-
|'''Pupil'''||The central opening in the iris, allowing and regulating the entry of light into the eye.
|-
|'''Retina'''||The sensory membrane that forms the inner lining of the eye containing rods and cones with the main function of photoreception. Nerve impulses in response to visual information are transmitted to the brain via the optic nerve.
|-
|'''Retinitis Pigmentosa'''||A chronic hereditary eye disease characterized by breakdown and loss of cells in the retina leading to progressive visual loss.
|-
|'''Sclera'''||The dense, white, fibrous membrane that, along with the cornea, forms the external protective covering of the eye
|-
|'''Tear film'''||A layer of tears which spreads over the eye, ultimately maintaining the health of the ocular surface by making the external surface smooth and clear.

|}

{{Glossary}}

==References==

<references/>

==External links==

<pubmed>26956898</pubmed>

2017 Group Project 4

2017-10-26T00:54:44Z

Z3416557:

{{ANAT2341Project2017header}}

=Eye Development=

==Introduction==

The eye is a complex sensory structure which allows a variety of species to intake and process visual information from the world around us. Most structures forming the human eye are developed between the embryonic weeks 3 through 10, deriving primarily from ectoderm, neural crest cells and mesenchyme.

This project page will start with a description of the functional anatomy of the adult eye, continue with a description and timeline of the embryonic formation and signaling pathways of important structures of the human eye and animal models and finish with an examination of congenital abnormalities, current research and pending questions for the near future.

We hope that this page provides you with an enjoyable, comprehensive introduction to the embryology of the eye (we have aimed to keep it a concise 'reachable' page!)

==Anatomy of the Adult Eye==

To discuss the key anatomical components of the eye, we will break down the eye in parts<ref>Chen, J., 2011. Handbook of Visual Display Technology. Springer Berlin Heidelberg. Chapter 2.1</ref>:

'''Supporting Structures (Orbit, Extraoccular Muscles, Lacrimal Gland, Eyelid)'''
[[File:22292144 10208413540209536 722417340 o.jpg|250px|thumb|right| '''Figure 1.''' Layers of the Eyeball]]
The orbit consists of a framework of bones and connective tissue which provide structural support and protection to the sensitive human eye. 7 bones contribute to the orbit of the eye: frontal, lacrimal, sphenoid, zygomatic, ethmoid, maxillary, palatine. Several openings exist in the orbital structure, 2 key fissures are the superior orbital fissure and inferior orbital fissure and the posterior optic canal. These openings allow cranial nerves passageway.

A set of 6 extraocular muscles allow for a strong voluntary control of the movement of the eye. These muscles include superior recuts, inferior rectus, lateral rectus, medial rectus, inferior oblique, superior oblique muscles. These muscles are some of the smallest in the human body and are designed to produce fast, controlled motion to focus on an object of interest.

The eyelid is the anterior covering of the eye, consisting of a thin fold of skin. It is controlled by the levitator palpabrae superioris muscle. Superio-laterally to the eyelid is the lacrimal gland, which serves to create a film of tear, an important component to keeping the anterior surface of the eye moist. The eyelid assists in this process by opening and closing, or blinking, which spreads the tear film across the surface of the eye. Debris caught in the tear film is excreted through the lacrimal duct which is located on the infero-medial surface of the eyelid.
[[File:22251179_10208414266827701_870733039_o.jpg|250px|thumb|right| '''Figure 2.''' Anterior Part of the Eye]]

'''Layers of the Eyeball (Sclera, Choroid, Retina)'''

The superficial layer of the eyeball is the sclera, a thick fibrous layer which becomes thicker as it extends posteriorly. The sclera is visible as the white part of our eye. It's function is to provide structural stability to the eye and serves as attachment for some extraocular insertions. Deep to the sclera is the choroid, a vascular network which provides nourishment to the layers of the eyeball and plays a large role in the growth of the eye. Deep to the choroid is the retina, a network of nerve fibers which transmit visual information. The retina contains 2 types of photoreceptors which convert visible light into nerve impulses. Rods work best in low light environments while cones work best in high light enthronements and detect colour and sharp detail.<ref>Curcio CA, Hendrickson AE. Organization and development of the primate photoreceptor mosaic. Prog Ret Ret. 1991;10:89–120.</ref>: The retina does not extend to the anterior part of the eyeball, unlike the sclera and choroid layers.

'''Anterior structure (Lens, Cornea, Pupil, Iris, Ciliary Body, Conjunctiva, Anterior Chamber)'''

The most anterior component of the eyeball is the cornea, which is a multilayered avascular transparent structure who's major function is to the refract light to assist image formation (contributes about 75% of total refraction). Continuous with cornea superiorly and inferiorly is the conjunctiva. Deep to the cornera is the iris, or the coloured ring visible in the eye. The iris consists of 2 muscles which act to enhance and diminish the size of the pupil, a hole in the middle of the iris allowing light to enter the eye. Deep to the pupil and iris is the lens, which is a transparent structure which contributes the other 25% of the eye's refractive power. The lens changes shape through accomodation controlled by the ciliary body muscles. The ciliary body is the anterior extension of the choroid. The function of the lens is to focus images by changing refractive power based on the position and depth of focal objects. In between the anterior surface of the lens and posterior surface of the cornea is the anterior chamber. This chamber is filled with aqueous humor supplied by the ciliary body, who's function is to provide nutrients to ocular structures and maintain intraocular pressure.
[[File:22251314_10208414283908128_862494115_o.jpg|250px|thumb|right| '''Figure 3.''' Posterior Part of the Eye]]

'''Posterior structure (Optic Nerve, Optic Disc, Macula, Fovea, Posterior Chamber)'''

In the posterior section of the retina is the macula, a central spot in which a high concentration of cone photoreceptors are found. The direct centre of the macula is called the fovea which contains solely cone photoreceptors. The fovea is the only part of the eye which can conduct 'perfect' 20/20 vision. It has a high workload and hence a strong vascular supporting structure<ref><pubmed>6462623</pubmed></ref>:. The most posterior part of the eye is the optic nerve (along with the central retinal artery and central retinal vein), which is responsible for transporting nerve impulses to the cerebral cortex for processing. The opening of the optic nerve is called the optic disc, which contains no photoreceptors and is a blind spot of the eye. Between the posterior surface of the lens, the retina and the optic disc is the posterior chamber. The posterior chamber contains a vitreous humour, a jelly like substance with a high viscosity.

==Embryonic Contributions==

Eye development is a complex process. It involves the formation of the retina and the lens, which we together call the eyeball. It also involves the formation of auxiliary eye structures which are the eyelid, lacrimal gland, and cornea. The retina is formed from the neuroectoderm, the lens from the surface ectoderm and the auxiliary tissues are formed from the head surface ectoderm, neural crest cells and the head mesoderm <ref name="PMC3104407><pubmed>PMC3104407</pubmed></ref>.

[[File:Stage14 sem2cl.jpg|300px|thumb|right| '''Figure 4.''' Stage 14]]

{| class="wikitable"
! style="background:#f4a941" | Embryonic contributions
! style="background:#f4a941" | Eye component
|-
| Neuroectoderm of the forebrain || Retina, Posterior layers of the iris, The optic nerve
|-
| Surface ectoderm of the head || The lens of the eye, The corneal epithelium
|-
| Mesoderm between the neuroectoderm and the surface ectoderm || The fibrous and vascular coats of the eye
|-
| Neural crest cells || Choroid, Sclera, Corneal endothelium
|}

==Timeline of embryonic development==

{| class="wikitable"
! style="background:#f4a941" | WEEK
! style="background:#f4a941" | DEVELOPMENT
|-
| 3-4 || Eye fields, Optic vesicles
|-
| 5-6 || Optic Cup, Lens Vesicle, Choroid Fissure, Hyaloid Artery
|-
| 7-8 || Cornea, Anterior Chamber, Pupillary Membrane, Lens, Retina
|-
| 8-10 || Eyelids
|-
| 9-15 || Iris, Ciliary Body
|}

==Carnegie Stages==

Carnegie Stages are a system of 23 stages used to describe developmental events of the vertebrate embryo. At stage 10 we see early signs related to eye development. The table below is an made of knowledge from Anthony A. Person's article <ref><pubmed>7364662</pubmed></ref>.

{| class="pretty table"
|-bgcolor = "DDCEF2"
|'''Stage'''
|'''Events'''
|-bgcolor="FAF5FF"
|'''Stage 10 (22 days)'''
|The optic primordium has developed. Two small grooves develop on each side of the developing forebrain in the neural folds - this is the optic grooves. The optic placode has begun to develop, which is seen by a small thickening of the surface ectoderm lateral to the hindbrain.
|-
|'''Stage 11 (24 days)'''
|Optic vesicle begins to form from the optic groove.

[[File:Stage11 histology-optic pit.jpg|300px|'''Figure 1.''' Stage 11]]
|-bgcolor="FAF5FF"
|'''Stage 12 (26 days)'''
|The optic vesicles have extended from the forbrain to the surface ectoderm. The optic vesicle now lies close to the surface ectoderm.
|-
|'''Stage 13 (28 days)'''
| The optic vesicle interacts with the surface ectoderm and will induce this ectoderm to form the lens placode, which is the precursor of the lens. Optic evagination differentiation makes it possible to identiy optic parts of retina, future pigmented layer of retina and optic stalk.

[[File:Stage_13_image_060.jpg|300px|'''Figure 2.''' Stage 13]]
|-bgcolor="FAF5FF"
|'''Stage 14 (32 days)'''
| The lens placode is indented by the lens pit and is cup-shaped.
|-
| '''Stage 15 (33 days)'''
| The lens pit will close and form a circle that separates from the surface ectoderm and becomes the lens vesicle. The lens vesicle and optic cub lie close to the surface ectoderm, which creates a slight elevation in the region of the eye.
|-bgcolor="FAF5FF"
| '''Stage 16 (37 days )'''
| The lens body has grown and now has a D-shaped lens cavity. First indication of the development of the eyelids visible as eyelid grooves above and below the eye.
|-
| '''Stage 17 - 19'''
| Retinal pigment is visible and the retinal fissure is almost closed. The eyes are still laterally placed but starts to take a more anterior position. The lower eyelid fold develops first and then the eyelid fold above the eye.
|-bgcolor="FAF5FF"
| '''Stage 18 (44 days)'''
| Mesenchyme invades the region between the lens epithelium and the surface ectoderm. The eyes have shifted to a more anterior position. The groove above and below the eyes are deeper but have not joined yet.
|-
| '''Stage 19 - 22'''
| The eyelid folds develop into the eyelids and the upper and the lower eyelids now meet at the outer canthus, which is the corner of the eye.

[[File:Stage 22 image 208.jpg|300px|'''Figure 3.''' Stage 22]]
|-bgcolor="FAF5FF"
| '''Stage 20 (51 days)'''
| The lens cavity is lost. The upper and lower lids meet laterally and medially. The eyelids now partly cover the eye. Lens suture begins to form.
|-
| '''Stage 23 (57 days)'''
| End of embryonic period. The face begins to look human. Eyelids closure is complete.
|-
|-bgcolor="FAF5FF"
|-
|}

==Development of the eye components==

===Introduction===

<html5media width=“480" height="360">https://www.youtube.com/embed/ghHDFWlfpoQ</html5media>

[[File:DevelopmentEye-PMC43029243.jpg|400px|thumb|right|'''Figure 5.''' Stages of lens formation in mouse embryos]]

The eye starts to develop at 22 days. The optic grooves (sulci) appears in the neural folds at the cranial end of the embryo. When the neural fold fuse to form the forebrain, the optic grooves will form '''optic vesicles'''. The optic vesicles are continuous cavities from the cavity of the forebrain and project from the wall of the forebrain and into the mesenchyme. The optic vesicle extends from the diencephalon and will come in contact with the surface ectoderm of the head. This induces the formation of a lens placode.

The surface ectoderm near the optic vesicles will thicken and form the '''lens placodes'''. The lens placodes will sink into the surface ectoderm and form '''lens pits'''. The edges of the lens pits will travel towards each other and fuse to form round '''lens vesicles''', which will later lose connection with the surface ectoderm. The optic vesicles do also keep developing - they will form double-walled '''optic cups''' which are connected to the brain by the '''optic stalk'''. The two layers of the optic cup will differentiate in different directions. The cells of the outer layer will produce melanin pigment and later become the '''pigmented retina'''. The cells of the inner layer of the optic cup will proliferate fast and develop glia, ganglion cells, interneurons and light-sensitive photoreceptor neurons. These cells are in the '''neural retina'''. The ganglion cells of the retina are neurons that send signals to the brain. The axons of the ganglion cells of the neural retina will grow in the wall of the optic stalk. The cavity in the optic nerve will start disappearing, and instead, the axons of the ganglion cells will form the '''optic nerve'''. The optic stalk is now the optic nerve <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>

The optic cups will fold inwards around the lens while the lens vesicles have grown inwards so they have fully lost their connection with the surface ectoderm, which locates them in the cavities of the optic cups. The retinal fissures (linear grooves) will develop and cover the ventral surface of the optic cups and down to the optic stalk. The retinal fissures contain vascular mesenchyme and hyaloid blood vessels will develop here. The hyaloid artery supplies the structures in the eye with blood and the hyaloid vein will return the blood from these structures <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

'''Formation of the optic vesicle'''

It is a specific area of the neural ectoderm that will become the optic vesicle - this happens because of a group of transcription factors - Six3, Pax6, and Rx1. These transcription factors are expressed in the most anterior tip of the neural plate. This area will split into bilateral regions and form the optic vesicles. The Pax6 protein has shown to be especially important for the development of the lens and retina. This protein is important for photoreceptive cells in all phyla. Pax 6 is also present in the murine forebrain, hindbrain, and nasal placodes, but the eyes are most sensitive its absence <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

The sonic hedgehog gene is important for the separation of the single eye field into two fields. If this gene is inhibited, the eye field will not split which will result in cyclopia, a single eye in the center of the face <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

===Retina===

[[File:Bailey463.jpg|400px|thumb|right|'''Figure 6.''' Diagram of developing lens and optic cup]]

The retina is the essential component of the eye with the primary function of photoreception <ref><pubmed>7084144</pubmed></ref>. Formation of the retina begins with the specification of retinal cells in the anterior neuroectoderm. First morphological sign of eye development is the formation of two lateral grooves in the anterior neuroectoderm, which is called the optic sulci. The cells of the optic sulci will evaginate and form the optic vesicle. The distal portion of the optic vesicle will form the retina and the proximal will form the optic stalk <ref><pubmed>18675797 </pubmed></ref>. The retina develops from the walls of the optic cup, these walls develop into the two layers of the retina. The thin, outer layer of the optic cup will become the pigment layer of the retina and the thick, inner layer of the optic cup will differentiate into the neural retina. Forkhead transcription factors are regulating the proliferation and differentiation of the retinal precursor cells. During the embryonic and early fetal periods, the two layers of the retina are separated which makes an intraretinal space. The intraretinal space is derived from the cavity of the optic cup. The two layers of the retina will fuse and the intraretinal space will gradually disappear <ref name="Larsen'sHumanEmbryology">Schoenwolf, G.C., Bleyl, S.B., Brauer, P.R., Francis-West, P.H. & Philippa H. (2015). Larsen's human embryology (5th ed.). New York; Edinburgh: Churchill Livingstone.</ref>.

When the lens is developing the inner layer of the optic cup starts to proliferate and forms a thick neuroepithelium which will later differentiate into the neural retina. The neural retina contains photoreceptors and the cell bodies of neurons and is the light-sensitive region of the retina. The axons of the ganglion cells in the neural retina grow in the wall of the optic stalk and will form the optic nerve <ref name="Larsen'sHumanEmbryology">Schoenwolf, G.C., Bleyl, S.B., Brauer, P.R., Francis-West, P.H. & Philippa H. (2015). Larsen's human embryology (5th ed.). New York; Edinburgh: Churchill Livingstone.</ref>.

===Lens===

Human lens induction occurs at around 28 days and is completed around day 56. The surface ectoderm will thicken near the optic vesicle and create the lens placode and later form the lens vesicle <ref><pubmed>20171212 </pubmed></ref>. Lens cells come from ectoderm and differentiate into either lens fibers or the lens epithelium. The anterior monolayer of epithelial cells of the lens will create the lens epithelium, which makes the sheet of cuboidal epithelium covering the anterior surface of the lens. The posterior lens vesicle cells will produce the linear primary fibre cells aligned parallel to the optic axis. These fibres will create the lens mass and form the embryonic lens nucleus. The lens epithelial cells will keep proliferating and produce new cells which generate a secondary lens fiber cells. This rows of cell will form the outer shells and keep the lens growing throughout life. This makes the eye lens unique - it will have an addition of new cells inside the surrounding capsule all the time <ref><pubmed>25406393</pubmed></ref>.

===Ciliary Body===

The ciliary body is a muscular and secretory tissue and is located directly behind the lens. The ciliary body forms part of the anterior segment of the eye and is an important regulator of eye physiology and the vision. The ciliary body produces the aqueous fluid which fills the eyes and nourishes the lens and cornea - this aqueous fluid function to keep the eye in a pressurized and inflated state, which is important the vision.The ciliary body also synthesizes collagenIX and tenasin-C <ref><pubmed>17275804</pubmed></ref>.

The ciliary body extends from the iris root (anteriorly) to the ora serrata (posteriorly). It consist of ciliary muscles and ciliary processes. Each ciliary process (fold) is covered by a double-layered secretory epithelium; the outer pigmented and the inner unpigmented (closes to the lens). The epithelial layers of the ciliary body comes from the retina of the optic cup. We see two different ciliary body epithelium: the inner non-pigmented ciliary epithelium which is connected with the neural retina and the outer pigmented ciliary epithelium which is connected with the retinal pigmented epithelium. The epithelium of the iris is the further anterior extension. The epithelial layers are associated with a stroma containing the ciliary muscle. The ciliary muscle is complex, but can be divided into three portions; anterior, posterior and internal <ref><pubmed>12127103</pubmed></ref>.

In the chick eye development, we see the mesenchyme grow together on the margin of the optic cup and will form the stroma of the ciliary body and the iris, which is located more anteriorly. It is unknown how if the lens has a role in inducing the secretory ciliary body epithelium and the muscular iris epithelium <ref><pubmed>17275804</pubmed></ref>.

===Iris===

The iris is the circular, pigmented muscular portion of the eye with a central aperture that is the pupil. The main function of this round muscle is to manipulate pupil diameter as an adjustment to various conditions and to control the amount of light entering the eye <ref name=’’21413392’’><pubmed>21413392</pubmed></ref>. This is influenced by dilator pupillae (radial) and sphincter pupillae (constricting) muscles. Iris pigmentation is dependent on the abundance and distribution of certain types of melanin in the posterior epithelium of the iris (eumelanin and pheomelanin) <ref name=’’21413392’’/>.

The Iris develops at the end of the third month of development. The iris is a thin layer and derives from the anterior rim of the optic cup <ref><pubmed>22219630</pubmed></ref>. The iris is formed by the pigment-containing internal and external layers of the optic cup and by a layer of vascularised connective tissue which also contains the pupillary muscles. Internal layers of the optic cup form the non-pigmented iris parts whereas the external layers of the optic cup develop into the pigmented epithelial structures. <ref name=’’18168498’’><pubmed>18168498</pubmed></ref>. Iris stroma develops as a result of neural crest cell migration – within this stroma, the dilator and constrictor muscles develop from the neuroectoderm of the optic cup. In the anterior of the eye, the optic epithelium is non-neural and matures as ciliary body and iris epithelia <ref name=’’18168498’’/>.

===Cornea===

The cornea is the unique, transparent and avascular component located at the most anterior section of the eye. It is composed of five layers stemming from the 3 main layers of epithelium, stroma and endothelium:

* Corneal epithelium (most anteriorly) – consisting of multiple layers of cells which rest on a basement membrane.
* Bowman’s membrane – a clear, acellular homogenous layer. This layer is a modified portion of the stroma and has no regenerative capacity as a response to damage <ref name=''7084144''><pubmed>7084144</pubmed></ref>.
* Corneal stroma – largest portion of the retina consisting of collagenous tissue.
* Descemet’s membrane – a homogenous, elastic true basement layer with a regenerative capacity.
* Corneal endothelium – a single layer of cuboidal cells responsible for the maintenance of the dehydrative nature of corneal tissue. <ref name=''7084144''/>.

Corneal development involves interactions between ectoderm-derived tissues. More specifically, the corneal epithelium arises from interactions between the cranial ectoderm and optic vesicles derived from the neural ectoderm <ref name=''26310148''><pubmed>26310148</ref></pubmed>. The neural tube and the adjacent ectoderm give rise to the neural crest cells which are multipotent with a migratory capacity. These cells contribute to the formation of corneal epithelium and the stromal cells. Innervation of the cornea stroma and epithelium is derived from both the neural crest and the ectodermal placode <ref name=''26310148''/>. The endothelium is comprised of differentiated neural crest cells which contribute to the later formation of Descemet’s membrane <ref><pubmed>6511224</pubmed></ref>.

===Aqueous Chambers===

There are two aqueous chambers of the eye: anterior and poster. These chambers are filled with a plasma-like fluid called aqueous humour and is produced by the ciliary body and trabecular meshwork in 3 main stages: diffusion, ultrafiltration and active secretion <ref><pubmed>6763801</pubmed></ref>. The main function of this fluid is to maintain the intraocular pressure as well as provide structural integrity to the round shape of the eyeball. This structure also has a role in the immune response and provides nutrition to the avascular tissue (e.g., the cornea and lens). <ref><pubmed>21293732</pubmed></ref>.

The anterior chamber is defined as the developed space posterior to the cornea (between the cornea and the iris) and develops at the stage of differentiation of the mesodermal portion of the iris <ref name=’’18168498’’/>. The space defining the posterior chamber develops as the mesenchyme between the lens and the peripheral iris.

===Choroid and Sclera===

The choroid and sclera are both surround the eye and are located adjacent to each other (the choroid lines the inner portion of the sclera). The sclera is the outer, fibrous white layer of the eye which functions as a supportive wall of the eye ball and is continuous with the cornea <ref name=''7084144''/> . The heavy vasculature of the choroid provides a major supply of oxygen and nourishment to the retina <ref><pubmed>20044062</pubmed></ref>.
They are derived from interactions between the neural crest and mesoderm-derived mesenchyme. The sclera forms as a result of condensation of the mesenchyme outside the optic cup <ref><pubmed>1628748</pubmed></ref>.
The choroid arises from the mesenchyme surrounding the optic vesicle and the cranial neural crest cells. The first vasculature structures appear in the choroid during week 15 in the form of arterioles and venules; veins and arteries become distinguishable by week 22 <ref name=’’2199235’’><pubmed>2199235</pubmed></ref>.

===Extraocular muscles===

The extraocular muscles are responsible for eye movement within the eye orbit – a critical aspect of sight and communication. 6 main muscles contribute to eye movement. These include: superior rectus, inferior rectus, lateral rectus, medial rectus, superior oblique and inferior oblique.

The development of these muscles is dependent on interactions between the eye, its muscles and the neural crest. <ref name=''21482859''><pubmed>21482859</pubmed></ref>.
Somites supplied by cranial nerve III forms 5 of the 6 extraocular muscles which form an interlocking tendinous ring made of fibrous connective tissue. The 5 muscles include the lateral, medial, superior and inferior rectus, and the superior oblique muscle. This common tendinous ring is known as the annulus of Zinn and surrounds the entry of the optic nerve. The remaining sixth muscle is the inferior oblique muscle and is separate from the aforementioned tendinous ring due to its distinct point of origin. <ref name=''21482859''/>.

===Eyelids===

The eyelids are upper and lower folds of skin functioning as a barrier protecting the anterior surface of the eye from direct local injury. Eyelids also regulate light exposure, distribute precorneal tear film over the corneal surface when blinking and are involved in functions involving tear flow <ref><pubmed>1993591</pubmed></ref>.
No sign of eyelid fold development is evident at week 5 however at this stage the lens pit begins to invaginate from the surface ectoderm <ref name=’’27124372’’><pubmed>27124372</pubmed></ref>. Week 6 initiates the timeline of eyelid development as small depressions emerge in the surface ectoderm both above and below the developing eye – these rapidly deepen to form the folds of the eyelids <ref name=‘’7364662’’><pubmed>7364662</pubmed></ref>. The lower eyelid fold develops first and, by the end of week 6, the lower fold is more distinct than the upper eyelid fold <ref><pubmed>21416630</pubmed></ref>. Week 7 marks the point at which both the upper and lower folds are distinctly developed and during this stage, the upper lid assumes its more dominant role <ref name=’’27124372’’/>. The eyelid is not fully closed - there is a gap between the folds and the cornea is slightly visible – they eventually undergo fusion in week 8 <ref name=’’27124372’’/>.

===Lacrimal Glands===

The lacrimal glands are exocrine glands located in the upper lateral region of each eye orbit which secrete the aqueous potion of the tear film. This film is continuously secreted and functions to clean and protect the external surface of the eye, keeping the environment constantly moist and preventing possible injury from dust and other particles <ref><pubmed>17001201</ref>.
Lacrimal gland morphogenesis is identified in three stages.

* The first is the presumptive glandular stage. This stage involves the thickening of the conjunctival superior fornix epithelium and the condensing of the surrounding mesenchyme <ref name=’’14635806’’><pubmed>14635806</pubmed></ref>.

* The second is the bud stage. This stage is considered the initial sign of glandular formation due to the development of nodular structures and lumina within epithelia buds <ref name=’’14635806’’/>.

* The third is the glandular maturity stage (week 9-16). In this stage, the lacrimal gland begins to morphologically mirror the adult gland <ref name=’’14635806’’/>.

==Signalling pathways and transcription factors involved throughout eye development==

===Eye field development===

Many signalling pathways and transcription factors are involved in the development of the eye field (which forms in addition to the telencephalon and diencephalon as part of division of the anterior neural plate). Eye progenitor cells are guided into the eye field region by fibroblast growth factor, bone morphogenetic protein and Wnt-signalling pathways <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>. Additionally, interactions between canonical and non-canonical Wnt-signalling have been shown to maintain the eye field border <ref name=’’16413771’><pubmed>16413771</pubmed></ref>.

The cells of the eye field express eye field transcription factors, some of which include Rx1/Rax, Pax6, Lhx2, Six3 and Otx2. Six3, Pax6, Otx2 and Rx1 specify retinal lineage and regulate progenitor cell movement to guide them to their correct locations <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>. Six3 also partly mediates Wnt-signalling repression, allowing for the development of the optic vesicles from the eye field <ref name=’’23684892 ’’><pubmed>23684892 </pubmed></ref>. Lhx2 maintains optic lineage in eye progenitor cells and suppresses the potential for differentiation towards different fates <ref name=’’23595746’’><pubmed>23595746</pubmed></ref>.

===Eye field division and progression to optic cup===

TGF-β, FGF and Shh family factors secreted by the axial mesoderm underlying the eye field initiate its splitting into two bilateral, symmetric eye primordia <ref name=’’23684892 ’’><pubmed>23684892 </pubmed></ref>. These factors also regulate the expression of transcription factors Pax2, Pax6, Vax1 and Vax2, thereby establishing the boundaries and patterning the proxiodistal and ventronasal axes of the optic vesicles <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>.

Despite the close relationship between cellular proliferation and morphogenesis, optic vesicle evagination does not appear to be mainly driven by proliferation <ref name=’’23684892 ’’><pubmed>23684892 </pubmed></ref>. Alternatively, it has been shown that retinoic acid has critical importance in optic vesicle evagination to form the optic cup <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>. Rx3 activity has also been observed to have involvement in optic vesicle evagination <ref name=’’23684892 ’’><pubmed>23684892 </pubmed></ref>.

===From optic cup to developed eye===

Lens placode maturation and lens development is dependent on Pax6 expression and regulation. During placode formation bone morphogenetic protein and fibroblast growth factor signalling regulate Pax6. Within the presumptive lens ectoderm, Pax6 is regulated by Six3 and Meis. However, within the presumptive epithelium Pax6 is a regulating factor, regulating the expression of Sox2 and eventually Six3 once the lens placode is formed <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>.

Meanwhile, in the primordial retina retinal progenitor cells become retinal ganglion cells through the expression of the basic helix-loop-helix transcription factor ath5 (which is regulated by Hh and Fgf signalling. The amacrine, horizontal and bipolar cells of the retina are generated by a variety of transcription factors, some of which include Pax6, Six3 and Foxn4 <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>. Crx and Otx2 positive cells progress towards photoreceptor fates and are further developed into rods and cones based on specific transcription factor expression (TRβ2 and RxRγ expression is required for cones, where as Nrl, Nr2e3 and Ascl1 expression is required for rods) <ref name=’’20648062’’><pubmed>20648062</pubmed></ref>. The transcription factors required for the development of the retinal pigment epithelium include Mitf, Otx1/Otx2 and Pax6. TGF-β, FGF, BMP and Hh signalling from the surrounding mesenchyme have also been shown to help induce retinal pigment epithelium fate in progenitor cells <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>.

Within the choroid, the expression and regulation of many different factors and signalling pathways is required for the development of proper arterial-venous connections, allowing for the functional circulation of nutrients and oxygen throughout the eye. VEGF, bFGF, PDGF and PEDF (from the retinal pigment epithelium) drive the development and maturation of choroidal blood vessels. Vascular patterning is regulated by the interactions between VEGF and Delta-like 4 factors. Additionally, Notch signalling has been shown to have importance in the formation of capillary beds <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>.

===Eye formation in the absence of the retina===

The gene Rx is a key component in the formation of retinal structures. Studies have shown that mice lacking Rx function do not form optic sulci or optic vesicles and do not have retina-specific gene expression. There has been made studies in human, medaka, zebrafish and Xenopus which suggest that Rx genes are required for the formation of the vertebrate retina. It is also shown that in Rx-deficient mouse embryos the mature lens does not develop. This indicates that retinal cells are necessary for lens formation, and if the mouse is lacking Rx gene, then it will not display any retina-specific gene expression <ref name="PMC3104407"/>.

It is thought that signaling from the optic vesicle is important to activate the lens-specific gene and the formation of the lens placode. If there are no retinal cells generated, then the morphogenesis of the optic cup does not take place and the lens will not form. The study also showed that elimination of β-catenin expression in the head surface ectoderm in Rx-deficient embryos would develop a lens-like structure even though there were no optic vesicle/cup. Elimination of β-catenin lead to upregulation of Pax6, which is a gene that has a key role in lens formation. This indicates that the optic vesicle/cup might not be required for lens formation. The lens developed smaller than in wild type embryos, which means that the optic cup/vesicle might have an effect on a determination of the size of the lens. It could be that the developing optic vesicle/cup shields the developing lens placode from signals for other tissues that could disturb the lens formation <ref name="PMC3104407"/>.

It is not fully understood if the formation of the auxiliary eye structures is dependent on the development of the eyeball and its components, the retina and the lens. A study made my Eric C. Swindell and al. showed that auxiliary eye structures form even in the absence of retinal morphogenesis and retina-specific gene expression. This indicates that there are two separate developmental processes involved in the formation of the eye and its associated structures. In the absence of the retina and the lens, we still see specific gene expression in the surface ectoderm initiating the formation of auxiliary eye structures like eyelids and lacrimal glands <ref name="PMC3104407"/>.

==Current research==

===Iris epithelium cells as a potential source for regenerative medicine for retinal pigment epithelium degeneration===

The retinal pigment epithelium (RPE) is a monolayer of neural-crest-derived cells and is located between the photoreceptors and the choroid. There are many disorders that involve dysfunctional RPE and leads to retinal degenerative diseases. There is no treatment for these diseases, therefore, one of the most promising future therapy for RPE related disorders is to replace the cells of the dysfunctional RPE <ref name="PMC5565104><pubmed>PMC5565104</pubmed></ref>..

Studies have focused on the development and use of induced pluripotent stem cells (iPSC) for cell replacement therapy. It is possible to differentiate iPSC in vitro towards RPE cells and use them for experimental transplantation studies in animal models. But an alternative strategy for a retinal replacement is based on transdifferentiation (direct conversion) and involves transforming an adult somatic cell into another adult somatic cell. Use of overexpression of cell-lineage specific genes can convert one cell into another cell type and skip the pluripotent state. Iris epithelium (IE) cells might be able to be transdifferentiated into the RPE since both RPE and IE are neuro-epithelia and has a common embryological origin - they both derive from neuroectoderm of the developing optic cup <ref name="PMC5565104"/>.

A study made by Anna Bennis et al. <ref name="PMC5565104"/>. has shown that the canonical pathways for the most highly expressed genes of the IE and the RPE were very similar. Wnt signaling pathways has shown to be active in the IE but not in the RPE. The Wnt signaling pathway consists of a group of signal transduction pathways that has an influence on cell fate determination and cell proliferation during embryonic development. Activation of Wnt SP makes it possible to reprogram somatic cells (also retinal neurons) into iPSC and is important for the differentiation of pluripotent stem cells to RPE cells. The high expression of Wnt SP genes in the iE suggests that the IE has a multipotent character during life and therefore could be transformed into RPE cells used for RPE replacement <ref name="PMC5565104"/>.

==Animal Models==
The zebrafish species is used to investigate ocular development, function and disease due to having the same morphology as other vertebrates including humans. The advantages of zebrafish include: they are able to quickly reach their sexual maturity, they behaviour can be observed quite early on because of their rapid development and most importantly, their embryos are translucent. Zebrafish is also active during the day therefore their retina contains a large number of diverse cone subtypes in additions to rods. <ref name="Zebrafish"> Glass, A. S. & Dahm, R. (2003). The Zebrafish as a Model Organism for Eye Development. ''Opthalmic Research, 36''(1), 4-24. doi: 10.1159/000076105</ref>

[[File:Chokh.png|250px|thumb|left| '''Figure 11.''' Wild type zebrafish vs chokh/rx3 knockout. Morphological differences with the absence of eyes in the knockout.]]
Through studying zebrafish, it was found that that a mutation in ''chokh/rx3'' gene results in the absence of eyes during the earliest stages of development due to failure of the retinal progenitor cells. <ref name="chokh">Loosli, F., Staub, W., Finger-Baier, K. C., Ober, E. A., Verkade, H., Wittbrodt, J. & Baier, H. (2003). Loss of eyes in zebrafish caused by mutation of chokh/rx3. ''EMBO Reports, 4''(9), 894-899. doi: 10.1038/sj.embor.embor919 </ref>. Optical vesicle is turned inside out and the neuronal differentiation is blocked. In this study, they have found that the DNA-binding homeodomain and the the entire C-terminal portion led to a nonsense mutation that resulted to complete loss of function in the eye. It was concluded that the gene ''chokh/rx3'' is important for the developing optic primordia.

==Congenital Abnormalities==
Although quite rare, abnormalities can occur during the embryonic development that causes serious effects to the features of the eyes, its function as well as the further normal development after birth. These abnormalities can occur unilaterally or bilaterally and it is also common for most reported cases to have more than one type of eye abnormalities at a time. Thus, the estimated prevalence statistics listed in the table can overlap.

{| class="wikitable"
! style="background:#f4a941" | Congenital Anomalies
! style="background:#f4a941" | Description
! style="background:#f4a941" | Epidemiology
|-
| Anopthalmia || The absence of the eyes.
| rowspan="2" | Prevalence: Anophthalmia-Microphthalmia Syndrome was estimated to be 5.3 per 100 000 cases <ref name="Anophthalmia">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: [[http://www.orpha.net/consor/cgi-bin/index.php]] </ref>
Cause: SOX2 gene mutation <ref name="SOX2 Gene"> Mauri, L., Franzoni, A., Scarcello, M.,
Sala, S., Garavelli, L. Modugno, A., ... Penco, S. (2015). SOX2, OTX2 and PAX6 analysis in subjects with anophthalmia and microphthalmia. ''European Journal of Medical Genetics, 58'', 66-70. doi: 10.1016/j.ejmg.2014.12.005 </ref>
|-
| Microphtalmia || Abnormal reduction in size of the eyeballs.
|-
| Keratoglobus || Structural abnormalities in the formation of the cornea - unknown cause - fixable through surgery<ref name="PMID23807384"><pubmed>23807384</pubmed></ref>
| Prevalence: understood to be a rare condition<ref name="PMID23807384"><pubmed>23807384</pubmed></ref>
|-
| Ptosis ('Lazy Eye')|| Structural abnormalities in the eyelid, can be congenital - specifically the failure of innervation of the oculomotor nerve for levator palpebrae superioris <ref name="PMID8759493"><pubmed>8759493</pubmed></ref> - fixable through surgery
| Prevalence: a relatively well known abnormality
|-
| Aphakia || Te absense of a lens in the eye, causing a loss of accommodation and hence far-sightedness. People with aphakia have relatively small pupils which are unable to dilate as much <ref name="PMID28913511"><pubmed>28913511</pubmed></ref>
| Prevalence: a rare congenital abnormality
|-
| Coloboma || A condition where parts of the eye is missing and failed to develop normally.
| Prevalence: Occular coloboma was estimated to be 8.0 per 100 000 cases <ref name="Anophthalmia">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: [[http://www.orpha.net/consor/cgi-bin/index.php]] </ref>
|-
| Aniridia || Complete or partial absence of the iris.
| Prevalence: Estimated to be 1.5 per 100 000 cases <ref name="Anophthalmia">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: [[http://www.orpha.net/consor/cgi-bin/index.php]] </ref>
|-
| Optic Nerve Hypoplasia || A condition where the optic nerves are underdeveloped.
| Prevalence: Reported to be the most common abnormality <ref name="The Optic Nerve Hypoplasia">Ryabets-Lienhard, A., Stewart, C., Borchert, M., & Geffner, M. E. (2016). The Optic Nerve Hypoplasia Spectrum - Review of the Literature and Clinical Guidelines. ''Advances in Pediatrics, 63'', 127-146. doi: 10.1016/j.yapd.2016.04.009 </ref>
*10.9 per 100 000 in United Kingdom
*17.3 per 100 000 cases in Sweden.
*6.3% of cases was reported in New Zealand
|-
|}

<gallery>

Anophthalmia.jpeg|'''Figure 8.''' Anopthalmia
Microphthalmia-500px.jpg| '''Figure 9.''' Microphthalmia
Opac_figure_7.jpg| '''Figure 10.''' Iris Coloboma
Opac figure 10.jpg| '''Figure 11.''' Partial Aniridia
</gallery>

==Future questions==
===Will it be possible to have eye transplants in the future?===
Lots of research has been done in making a whole-eye transplantation successful in order to finally cure blindness. Blindness is a worldwide problem and is currently untreatable due to the fact that retinal ganglion cells and the optic nerves do not regenerate. This can result from diseases including macular degeneration and end of stage glaucoma. The first successful eye transplantation was led by Stone and Cole in 1943<ref name="Return of Vision"> Stone, L. S. & Cole, C. H. (1943). Grafted Eyes of Young and Old Adult Salamanders (Amblystoma Punctatum) Showing Return of Vision. ''Yale Journal of Biology and Medicine, 15''(5), 735-754.2. PMCID: PMC2601300</ref> investigating 104 samples of the salamander species, ''Amblystoma Punctatum'', and one of its eyes were either implanted back into the same animal or it was completely transplanted to a new host. It was reported that circulation in the iris was re-established, retina was able to regenerate, a new optic nerve was connected to the brain through the optic chiasma and ocular movements were regained. Vision was reestablished by the second month. In a more recent study, in 2015, Li et al.<ref name="Structural Integrity"> Li, Y., Komatsu, C., Wang, B., Miller, M., Wang, H., van der Merwe, Y., Ho, L., Kostereva, N., Zhang, W., Xiao, B., Davidson, E., Solari, M., Steketee, M. B., Guo, S., Kagemann, L., Wollstein, G., Schuman, J., Chan, K., Gorantla, V. S., Washington, K. M. (2015). Abstract 112: Evaluation of Viability, Structural Integrity and Functional Outcome after Whole Eye Transplantation. ''Plastic & Reconstructive Surgery, 135''(5), 82. "PMC2601300"</ref> investigated the feasibility of eye transplantation by observing the surviving 15 rat models out of the original 22. They were able to confirm the integrity and functional return of vision after whole-eye surgeries with the aid of advance techniques that are available today. The Ear and Eye Foundation of Pittsburgh<ref>'''Ear and Eye Foundation of Pittsburgh''': https://eyeandear.org/our-research/ophthalmology/the-whole-eye-transplant-project</ref> is an organization that is currently running a project with lead researchers to discover a way for the optic nerves to regenerate and to cure blindness by 2020.

===Will the bionic eye pass clinical trials in the next few years?===
[[File:BionicEye.jpg|250px|thumb|left| '''Figure 12.''' Bionic Eye Diagram]]

The bionic eye is an external visual device that has been in the making for the last several years. It hopes to bring back full vision through the aid of a pair of glasses with a camera attached to it, which then transmits high-frequency radio signals to the microchip implanted in the users' eye. These signals are converted into electrical impulses by the electrodes implanted in the chip, which then stimulates the retinal cells and passes through the optic nerve. Electrical impulses travels to the vision processing centres in the brain and these are then interpreted as an image. At the moment, users must learn to understand light flashes and visual patterns and convert them into images they can interpret. Current prototypes require the users to have a previously working eyes, which means their optic nerves must still be relatively healthy and their visual cortex must be developed. Patients who have suffered from retinitis pigmentosa and age-related macular degeneration would benefit this technology. Bionic Vision Australia<ref>'''Bionic Vision Australia''': http://bionicvision.org.au/about/research_plan</ref> is one of the leading organisations that are aiming to treat blindness and are set to perform clinical trials on two of the devices of the bionic eye implants soon. Their objectives are to develop strategies that can improve the affected visual pathway to the brain by stimulating the remaining working retinal cells and also develop safe surgical procedures.

==Glossary==

{| class="pretty table"
|-bgcolor = "DDCEF2"
|'''Term'''
|'''Definition'''
|-bgcolor="FAF5FF"
|'''Age-related macular degeneration'''||An eye disease with its onset usually after age 60 that can progressively destroy the macula, the central portion of the retina, impairing central vision.
|-
|'''Aqueous humour'''||A transparent fluid similar to plasma with low protein concentrations secreted by the ciliary epithelium.
|-
|'''Choroid'''||The pigmented vascular layer of the eye located between the retina and sclera.
|-
|'''Choroid fissure'''||A ventral groove formed by the invagination of the optic cup located at the bottom of the optic vesicle through which blood vessels enter the eye.
|-
|'''Ciliary body'''||The connection between the iris and choroid consisting of the ciliary muscle, ciliary processes and the ciliary ring. Alters the shape of the lens and ciliary epithelium in order to focus on an image.
|-
|'''Cornea'''||The transparent anterior part of the external coat of the eye covering the iris and pupil and continuous with the sclera.
|-
|'''Ectoderm||The outermost primary germ cell layer in the early embryo.
|-
|'''Endoderm||The innermost primary germ cell layer in the early embryo.
|-
|'''Ectodermal placode'''||A neurogenic placode consisting of an area of thickened epithelium in the embryonic head ectoderm layer that gives rise to neurons and other structures of the sensory system.
|-
|'''Extraocular muscles'''||Muscles controlling eye movement.
|-
|'''Fovea'''||A small depression in the retina where visual acuity is the highest.
|-
|'''Hyaloid vasculature'''||The temporary circulatory system in fetal eyes which spontaneously degenerate when the retinal blood vessels begin to develop.
|-
|'''Intraocular pressure'''||Fluid pressure inside the eye created through continued renewal of fluids.
|-
|'''Iris'''||The coloured muscular ring surrounding the pupil which manipulates the diameter and size of the pupil and controls the amount of light entering the eye.
|-
|'''Lens'''||The transparent biconvex structure posterior to the iris with the main function of focusing light onto the retina in order to form clear images of objects at various distances.
|-
|'''Lens pit'''||A pit-like depression in the fetal head where the lens develops.
|-
|'''Lens placode'''||The placode developing in the ectoderm overlying the optic vesicle, eventually becoming the lens of the eye.
|-
|'''Lens vesicle'''||The ectodermal invagination in the embryo formed opposite the optic cup and gives rise to the lens.
|-
|'''Lumina'''||the central cavity of a tubular structure.
|-
|'''Macula'''||An oval-shaped pigmented area where there is the largest density of cone cells and is involved in producing the sharpness of central vision.
|-
|'''Mesenchyme'''||Loosely organised embryonic connective tissue originating from the mesoderm.
|-
|'''Neural crest'''||A temporary group of embryonic ectodermal cells.
|-
|'''Neural retina'''||Refers to three layers of neural cells within the retina (photoreceptor cells, bipolar cells and ganglion cells).
|-
|'''Neural tube'''||A hollow tubular structure as a result of neural plate folding which later develops into the brain and spinal cord.
|-
|'''Neuroepithelium'''||Epithelium consisting of specialised cells which detect sensory triggers for reception of external stimuli.
|-
|'''Optic cup'''||A structure of the diencephalon formed after optic vesicle folding. This structure gives rise to the retina.
|-
|'''Optic groove'''||Two small grooves on each side of the developing forebrain in the neural folds. Also chiasmatic groove.
|-
|'''Optic nerve'''||Cranial nerve II which transmits impulses to the brain from visual information detected by the photoreceptive retina.
|-
|'''Optic stalk'''||Pair of slender embryonic structures that give rise to the optic nerve.
|-
|'''Optic vesicle'''||An evagination of each lateral all of the embryonic vertebrate forebrain from which the nervous structures of the eye develop.
|-
|'''Pupil'''||The central opening in the iris, allowing and regulating the entry of light into the eye.
|-
|'''Retina'''||The sensory membrane that forms the inner lining of the eye containing rods and cones with the main function of photoreception. Nerve impulses in response to visual information are transmitted to the brain via the optic nerve.
|-
|'''Retinitis Pigmentosa'''||A chronic hereditary eye disease characterized by breakdown and loss of cells in the retina leading to progressive visual loss.
|-
|'''Sclera'''||The dense, white, fibrous membrane that, along with the cornea, forms the external protective covering of the eye
|-
|'''Tear film'''||A layer of tears which spreads over the eye, ultimately maintaining the health of the ocular surface by making the external surface smooth and clear.

|}

{{Glossary}}

==References==

<references/>

==External links==

<pubmed>26956898</pubmed>

2017 Group Project 4

2017-10-26T00:45:55Z

Z3416557:

{{ANAT2341Project2017header}}

=Eye Development=

==Introduction==

The eye is a complex sensory structure which allows a variety of species to intake and process visual information from the world around us. Most structures forming the human eye are developed between the embryonic weeks 3 through 10, deriving primarily from ectoderm, neural crest cells and mesenchyme.

This project page will start with a description of the functional anatomy of the adult eye, continue with a description and timeline of the embryonic formation and signaling pathways of important structures of the human eye and animal models and finish with an examination of congenital abnormalities, current research and pending questions for the near future.

We hope that this page provides you with an enjoyable, comprehensive introduction to the embryology of the eye (we have aimed to keep it a 'reachable' page!)

==Anatomy of the Adult Eye==

To discuss the key anatomical components of the eye, we will break down the eye in parts<ref>Chen, J., 2011. Handbook of Visual Display Technology. Springer Berlin Heidelberg. Chapter 2.1</ref>:

'''Supporting Structures (Orbit, Extraoccular Muscles, Lacrimal Gland, Eyelid)'''
[[File:22292144 10208413540209536 722417340 o.jpg|250px|thumb|right| '''Figure 1.''' Layers of the Eyeball]]
The orbit consists of a framework of bones and connective tissue which provide structural support and protection to the sensitive human eye. 7 bones contribute to the orbit of the eye: frontal, lacrimal, sphenoid, zygomatic, ethmoid, maxillary, palatine. Several openings exist in the orbital structure, 2 key fissures are the superior orbital fissure and inferior orbital fissure and the posterior optic canal. These openings allow cranial nerves passageway.

A set of 6 extraoccular muscles allow for a strong voluntary control of the movement of the eye. These muscles include superior recuts, inferior rectus, lateral rectus, medial rectus, inferior oblique, superior oblique muscles. These muscles are some of the smallest in the human body and are designed to produce fast, controlled motion to focus on an object of interest.

The eyelid is the anterior covering of the eye, consisting of a thin fold of skin. It is controlled by the levitator palpabrae superioris muscle. Superio-laterally to the eyelid is the lacrimal gland, which serves to create a film of tear, an important component to keeping the anterior surface of the eye moist. The eyelid assists in this process by opening and closing, or blinking, which spreads the tear film across the surface of the eye. Debris caught in the tear film is excreted through the lacrimal duct which is located on the infero-medial surface of the eyelid.
[[File:22251179_10208414266827701_870733039_o.jpg|250px|thumb|right| '''Figure 2.''' Anterior Part of the Eye]]

'''Layers of the Eyeball (Sclera, Choroid, Retina)'''

The superficial layers of the eyeball is the sclera, a thick fibrous layer which becomes thicker as it extends posteriorly. The sclera is the visible as the white part of our eye. It's function is to provide structural stability to the eye and serves as attachment for some extraoccular insertions. Deep to the sclera is the choroid, a vascular network which provides nourishment to the layers of the eyeball and plays a large role in the growth of the eye. Deep to the choroid is the retina, a network of nerve fibers which transmit visual information. The retina contains 2 types of photoreceptors which convert visible light into nerve impulses. Rods work best in low light environments while cones work best in high light enthronements and detect colour and sharp detail.<ref>Curcio CA, Hendrickson AE. Organization and development of the primate photoreceptor mosaic. Prog Ret Ret. 1991;10:89–120.</ref>: The retina does not extend to the anterior part of the eyeball, unlike the sclera and choroid layers.

'''Anterior structure (Lens, Cornea, Pupil, Iris, Ciliary Body, Conjunctiva Anterior Chamber)'''

The most anterior component of the eyeball is the cornea, which is a multilayered avascular transparent structure who's major function to the refract light to assist image formation (contributes about 75% of total refraction). Continuous with cornea superiorly and inferiorly is the conjunctiva. Deep to the cornera is the iris, or the coloured ring visible in the eye. The iris consists of 2 muscles which act to enhance and diminish the size of the pupil, a hole in the middle of the iris allowing light to enter the eye. Deep to the pupil and iris is the lens, which is a transparent structure which contributes the other 25% of the eye's refractive power. The lens changes shape through accomodation controlled by the ciliary body muscles. The ciliary body is the anterior extension of the choroid. The function of the lens is to focus images by changing refractive power based on the position and depth of focal objects. In between the anterior surface of the lens and posterior surface of the cornea is the anterior chamber. This chamber is filled with aqueous humor supplied by the ciliary body, who's function is to provide nutrients to ocular structures and maintain intraocular pressure.
[[File:22251314_10208414283908128_862494115_o.jpg|250px|thumb|right| '''Figure 3.''' Posterior Part of the Eye]]

'''Posterior structure (Optic Nerve, Optic Disc, Macula, Fovea, Posterior Chamber)'''

In the posterior section of the retina is the macula, a central spot in which a high concentration of cone photoreceptors are found. The direct centre of the macula is called the fovea which contains solely cone photoreceptors. The fovea is only part of the eye which can conduct 'perfect' 20/20 vision. It has a high workload and hence a strong vascular supporting structure<ref><pubmed>6462623</pubmed></ref>:. The most posterior part of the eye is the optic nerve (along with the central retinal artery and central retinal vein), which is responsible for transporting nerve impulses to the cerebral cortex for processing. The opening of the optic nerve is called the optic disc, which contains no photoreceptors and is a blind spot of the eye. Between the posterior surface of the lens, the retina and the optic disc is the posterior chamber. The posterior chamber contains a vitreous humour, a jelly like substance with a high viscosity.

==Embryonic Contributions==

Eye development is a complex process. It involves the formation of the retina and the lens, which we together call the eyeball. It also involves the formation of auxiliary eye structures which are the eyelid, lacrimal gland, and cornea. The retina is formed from the neuroectoderm, the lens from the surface ectoderm and the auxiliary tissues are formed from the head surface ectoderm, neural crest cells and the head mesoderm <ref name="PMC3104407><pubmed>PMC3104407</pubmed></ref>.

[[File:Stage14 sem2cl.jpg|300px|thumb|right| '''Figure 4.''' Stage 14]]

{| class="wikitable"
! style="background:#f4a941" | Embryonic contributions
! style="background:#f4a941" | Eye component
|-
| Neuroectoderm of the forebrain || Retina, Posterior layers of the iris, The optic nerve
|-
| Surface ectoderm of the head || The lens of the eye, The corneal epithelium
|-
| Mesoderm between the neuroectoderm and the surface ectoderm || The fibrous and vascular coats of the eye
|-
| Neural crest cells || Choroid, Sclera, Corneal endothelium
|}

==Timeline of embryonic development==

{| class="wikitable"
! style="background:#f4a941" | WEEK
! style="background:#f4a941" | DEVELOPMENT
|-
| 3-4 || Eye fields, Optic vesicles
|-
| 5-6 || Optic Cup, Lens Vesicle, Choroid Fissure, Hyaloid Artery
|-
| 7-8 || Cornea, Anterior Chamber, Pupillary Membrane, Lens, Retina
|-
| 8-10 || Eyelids
|-
| 9-15 || Iris, Ciliary Body
|}

==Carnegie Stages==

Carnegie Stages are a system of 23 stages used to describe developmental events of the vertebrate embryo. At stage 10 we see early signs related to eye development. The table below is an made of knowledge from Anthony A. Person's article <ref><pubmed>7364662</pubmed></ref>.

{| class="pretty table"
|-bgcolor = "DDCEF2"
|'''Stage'''
|'''Events'''
|-bgcolor="FAF5FF"
|'''Stage 10 (22 days)'''
|The optic primordium has developed. Two small grooves develop on each side of the developing forebrain in the neural folds - this is the optic grooves. The optic placode has begun to develop, which is seen by a small thickening of the surface ectoderm lateral to the hindbrain.
|-
|'''Stage 11 (24 days)'''
|Optic vesicle begins to form from the optic groove.

[[File:Stage11 histology-optic pit.jpg|300px|'''Figure 1.''' Stage 11]]
|-bgcolor="FAF5FF"
|'''Stage 12 (26 days)'''
|The optic vesicles have extended from the forbrain to the surface ectoderm. The optic vesicle now lies close to the surface ectoderm.
|-
|'''Stage 13 (28 days)'''
| The optic vesicle interacts with the surface ectoderm and will induce this ectoderm to form the lens placode, which is the precursor of the lens. Optic evagination differentiation makes it possible to identiy optic parts of retina, future pigmented layer of retina and optic stalk.

[[File:Stage_13_image_060.jpg|300px|'''Figure 2.''' Stage 13]]
|-bgcolor="FAF5FF"
|'''Stage 14 (32 days)'''
| The lens placode is indented by the lens pit and is be cup-shaped.
|-
| '''Stage 15 (33 days)'''
| The lens pit will close and form a circle that separates from the surface ectoderm and becomes the lens vesicle. The lens vesicle and optic cub lie close to the surface ectoderm, which creates a slight elevation in the region of the eye.
|-bgcolor="FAF5FF"
| '''Stage 16 (37 days )'''
| The lens body has grown and now has a D-shaped lens cavity. First indication of the development of the eyelids visible as eyelid grooves above and below the eye.
|-
| '''Stage 17 - 19'''
| Retinal pigment is visible and the retinal fissure is almost closed. The eyes are still laterally placed but starts to take a more anterior position. The lower eyelid fold develops first and then the eyelid fold above the eye.
|-bgcolor="FAF5FF"
| '''Stage 18 (44 days)'''
| Mesenchyme invades the region between the lens epithelium and the surface ectoderm. The eyes have shifted to a more anterior position. The groove above and below the eyes are deeper but have not joined yet.
|-
| '''Stage 19 - 22'''
| The eyelid folds develop into the eyelids and the upper and the lower eyelids now meet at the outer canthus, which is the corner of the eye.

[[File:Stage 22 image 208.jpg|300px|'''Figure 3.''' Stage 22]]
|-bgcolor="FAF5FF"
| '''Stage 20 (51 days)'''
| The lens cavity is lost. The upper and lower lids meet laterally and medially. The eyelids now partly cover the eye. Lens suture begins to form.
|-
| '''Stage 23 (57 days)'''
| End of embryonic period. The face begins to look human. Eyelids closure is complete.
|-
|-bgcolor="FAF5FF"
|-
|}

==Development of the eye components==

===Introduction===

<html5media width=“480" height="360">https://www.youtube.com/embed/ghHDFWlfpoQ</html5media>

[[File:DevelopmentEye-PMC43029243.jpg|400px|thumb|right|'''Figure 5.''' Stages of lens formation in mouse embryos]]

The eye starts to develop at 22 days. The optic grooves (sulci) appears in the neural folds at the cranial end of the embryo. When the neural fold fuse to form the forebrain, the optic grooves will form '''optic vesicles'''. The optic vesicles are continuous cavities from the cavity of the forebrain and project from the wall of the forebrain and into the mesenchyme. The optic vesicle extends from the diencephalon and will come in contact with the surface ectoderm of the head. This induces the formation of a lens placode.

The surface ectoderm near the optic vesicles will thicken and form the '''lens placodes'''. The lens placodes will sink into the surface ectoderm and form '''lens pits'''. The edges of the lens pits will travel towards each other and fuse to form round '''lens vesicles''', which will later lose connection with the surface ectoderm. The optic vesicles do also keep developing - they will form double-walled '''optic cups''' which are connected to the brain by the '''optic stalk'''. The two layers of the optic cup will differentiate in different directions. The cells of the outer layer will produce melanin pigment and later become the '''pigmented retina'''. The cells of the inner layer of the optic cup will proliferate fast and develop glia, ganglion cells, interneurons and light-sensitive photoreceptor neurons. These cells are in the '''neural retina'''. The ganglion cells of the retina are neurons that send signals to the brain. The axons of the ganglion cells of the neural retina will grow in the wall of the optic stalk. The cavity in the optic nerve will start disappearing, and instead, the axons of the ganglion cells will form the '''optic nerve'''. The optic stalk is now the optic nerve <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>

The optic cups will fold inwards around the lens while the lens vesicles have grown inwards so they have fully lost their connection with the surface ectoderm, which locates them in the cavities of the optic cups. The retinal fissures (linear grooves) will develop and cover the ventral surface of the optic cups and down to the optic stalk. The retinal fissures contain vascular mesenchyme and hyaloid blood vessels will develop here. The hyaloid artery supplies the structures in the eye with blood and the hyaloid vein will return the blood from these structures <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

'''Formation of the optic vesicle'''

It is a specific area of the neural ectoderm that will become the optic vesicle - this happens because of a group of transcription factors - Six3, Pax6, and Rx1. These transcription factors are expressed in the most anterior tip of the neural plate. This area will split into bilateral regions and form the optic vesicles. The Pax6 protein has shown to be especially important for the development of the lens and retina. This protein is important for photoreceptive cells in all phyla. Pax 6 is also present in the murine forebrain, hindbrain, and nasal placodes, but the eyes are most sensitive its absence <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

The sonic hedgehog gene is important for the separation of the single eye field into two fields. If this gene is inhibited, the eye field will not split which will result in cyclopia, a single eye in the center of the face <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

===Retina===

[[File:Bailey463.jpg|400px|thumb|right|'''Figure 6.''' Diagram of developing lens and optic cup]]

The retina is the essential component of the eye with the primary function of photoreception <ref><pubmed>7084144</pubmed></ref>. Formation of the retina begins with the specification of retinal cells in the anterior neuroectoderm. First morphological sign of eye development is the formation of two lateral grooves in the anterior neuroectoderm, which is called the optic sulci. The cells of the optic sulci will evaginate and form the optic vesicle. The distal portion of the optic vesicle will form the retina and the proximal will form the optic stalk <ref><pubmed>18675797 </pubmed></ref>. The retina develops from the walls of the optic cup, these walls develop into the two layers of the retina. The thin, outer layer of the optic cup will become the pigment layer of the retina and the thick, inner layer of the optic cup will differentiate into the neural retina. Forkhead transcription factors are regulating the proliferation and differentiation of the retinal precursor cells. During the embryonic and early fetal periods, the two layers of the retina are separated which makes an intraretinal space. The intraretinal space is derived from the cavity of the optic cup. The two layers of the retina will fuse and the intraretinal space will gradually disappear <ref name="Larsen'sHumanEmbryology">Schoenwolf, G.C., Bleyl, S.B., Brauer, P.R., Francis-West, P.H. & Philippa H. (2015). Larsen's human embryology (5th ed.). New York; Edinburgh: Churchill Livingstone.</ref>.

When the lens is developing the inner layer of the optic cup starts to proliferate and forms a thick neuroepithelium which will later differentiate into the neural retina. The neural retina contains photoreceptors and the cell bodies of neurons and is the light-sensitive region of the retina. The axons of the ganglion cells in the neural retina grow in the wall of the optic stalk and will form the optic nerve <ref name="Larsen'sHumanEmbryology">Schoenwolf, G.C., Bleyl, S.B., Brauer, P.R., Francis-West, P.H. & Philippa H. (2015). Larsen's human embryology (5th ed.). New York; Edinburgh: Churchill Livingstone.</ref>.

===Lens===

Human lens induction occurs at around 28 days and is completed around day 56. The surface ectoderm will thicken near the optic vesicle and create the lens placode and later form the lens vesicle <ref><pubmed>20171212 </pubmed></ref>. Lens cells come from ectoderm and differentiate into either lens fibers or the lens epithelium. The anterior monolayer of epithelial cells of the lens will create the lens epithelium, which makes the sheet of cuboidal epithelium covering the anterior surface of the lens. The posterior lens vesicle cells will produce the linear primary fibre cells aligned parallel to the optic axis. These fibres will create the lens mass and form the embryonic lens nucleus. The lens epithelial cells will keep proliferating and produce new cells which generate a secondary lens fiber cells. This rows of cell will form the outer shells and keep the lens growing throughout life. This makes the eye lens unique - it will have an addition of new cells inside the surrounding capsule all the time <ref><pubmed>25406393</pubmed></ref>.

===Ciliary Body===

The ciliary body is a muscular and secretory tissue and is located directly behind the lens. The ciliary body forms part of the anterior segment of the eye and is an important regulator of eye physiology and the vision. The ciliary body produces the aqueous fluid which fills the eyes and nourishes the lens and cornea - this aqueous fluid function to keep the eye in a pressurized and inflated state, which is important the vision.The ciliary body also synthesizes collagenIX and tenasin-C <ref><pubmed>17275804</pubmed></ref>.

The ciliary body extends from the iris root (anteriorly) to the ora serrata (posteriorly). It consist of ciliary muscles and ciliary processes. Each ciliary process (fold) is covered by a double-layered secretory epithelium; the outer pigmented and the inner unpigmented (closes to the lens). The epithelial layers of the ciliary body comes from the retina of the optic cup. We see two different ciliary body epithelium: the inner non-pigmented ciliary epithelium which is connected with the neural retina and the outer pigmented ciliary epithelium which is connected with the retinal pigmented epithelium. The epithelium of the iris is the further anterior extension. The epithelial layers are associated with a stroma containing the ciliary muscle. The ciliary muscle is complex, but can be divided into three portions; anterior, posterior and internal <ref><pubmed>12127103</pubmed></ref>.

In the chick eye development, we see the mesenchyme grow together on the margin of the optic cup and will form the stroma of the ciliary body and the iris, which is located more anteriorly. It is unknown how if the lens has a role in inducing the secretory ciliary body epithelium and the muscular iris epithelium <ref><pubmed>17275804</pubmed></ref>.

===Iris===

The iris is the circular, pigmented muscular portion of the eye with a central aperture that is the pupil. The main function of this round muscle is to manipulate pupil diameter as an adjustment to various conditions and to control the amount of light entering the eye <ref name=’’21413392’’><pubmed>21413392</pubmed></ref>. This is influenced by dilator pupillae (radial) and sphincter pupillae (constricting) muscles. Iris pigmentation is dependent on the abundance and distribution of certain types of melanin in the posterior epithelium of the iris (eumelanin and pheomelanin) <ref name=’’21413392’’/>.

The Iris develops at the end of the third month of development. The iris is a thin layer and derives from the anterior rim of the optic cup <ref><pubmed>22219630</pubmed></ref>. The iris is formed by the pigment-containing internal and external layers of the optic cup and by a layer of vascularised connective tissue which also contains the pupillary muscles. Internal layers of the optic cup form the non-pigmented iris parts whereas the external layers of the optic cup develop into the pigmented epithelial structures. <ref name=’’18168498’’><pubmed>18168498</pubmed></ref>. Iris stroma develops as a result of neural crest cell migration – within this stroma, the dilator and constrictor muscles develop from the neuroectoderm of the optic cup. In the anterior of the eye, the optic epithelium is non-neural and matures as ciliary body and iris epithelia <ref name=’’18168498’’/>.

===Cornea===

The cornea is the unique, transparent and avascular component located at the most anterior section of the eye. It is composed of five layers stemming from the 3 main layers of epithelium, stroma and endothelium:

* Corneal epithelium (most anteriorly) – consisting of multiple layers of cells which rest on a basement membrane.
* Bowman’s membrane – a clear, acellular homogenous layer. This layer is a modified portion of the stroma and has no regenerative capacity as a response to damage <ref name=''7084144''><pubmed>7084144</pubmed></ref>.
* Corneal stroma – largest portion of the retina consisting of collagenous tissue.
* Descemet’s membrane – a homogenous, elastic true basement layer with a regenerative capacity.
* Corneal endothelium – a single layer of cuboidal cells responsible for the maintenance of the dehydrative nature of corneal tissue. <ref name=''7084144''/>.

Corneal development involves interactions between ectoderm-derived tissues. More specifically, the corneal epithelium arises from interactions between the cranial ectoderm and optic vesicles derived from the neural ectoderm <ref name=''26310148''><pubmed>26310148</ref></pubmed>. The neural tube and the adjacent ectoderm give rise to the neural crest cells which are multipotent with a migratory capacity. These cells contribute to the formation of corneal epithelium and the stromal cells. Innervation of the cornea stroma and epithelium is derived from both the neural crest and the ectodermal placode <ref name=''26310148''/>. The endothelium is comprised of differentiated neural crest cells which contribute to the later formation of Descemet’s membrane <ref><pubmed>6511224</pubmed></ref>.

===Aqueous Chambers===

There are two aqueous chambers of the eye: anterior and poster. These chambers are filled with a plasma-like fluid called aqueous humour and is produced by the ciliary body and trabecular meshwork in 3 main stages: diffusion, ultrafiltration and active secretion <ref><pubmed>6763801</pubmed></ref>. The main function of this fluid is to maintain the intraocular pressure as well as provide structural integrity to the round shape of the eyeball. This structure also has a role in the immune response and provides nutrition to the avascular tissue (e.g., the cornea and lens). <ref><pubmed>21293732</pubmed></ref>.

The anterior chamber is defined as the developed space posterior to the cornea (between the cornea and the iris) and develops at the stage of differentiation of the mesodermal portion of the iris <ref name=’’18168498’’/>. The space defining the posterior chamber develops as the mesenchyme between the lens and the peripheral iris.

===Choroid and Sclera===

The choroid and sclera are both surround the eye and are located adjacent to each other (the choroid lines the inner portion of the sclera). The sclera is the outer, fibrous white layer of the eye which functions as a supportive wall of the eye ball and is continuous with the cornea <ref name=''7084144''/> . The heavy vasculature of the choroid provides a major supply of oxygen and nourishment to the retina <ref><pubmed>20044062</pubmed></ref>.
They are derived from interactions between the neural crest and mesoderm-derived mesenchyme. The sclera forms as a result of condensation of the mesenchyme outside the optic cup <ref><pubmed>1628748</pubmed></ref>.
The choroid arises from the mesenchyme surrounding the optic vesicle and the cranial neural crest cells. The first vasculature structures appear in the choroid during week 15 in the form of arterioles and venules; veins and arteries become distinguishable by week 22 <ref name=’’2199235’’><pubmed>2199235</pubmed></ref>.

===Extraocular muscles===

The extraocular muscles are responsible for eye movement within the eye orbit – a critical aspect of sight and communication. 6 main muscles contribute to eye movement. These include: superior rectus, inferior rectus, lateral rectus, medial rectus, superior oblique and inferior oblique.

The development of these muscles is dependent on interactions between the eye, its muscles and the neural crest. <ref name=''21482859''><pubmed>21482859</pubmed></ref>.
Somites supplied by cranial nerve III forms 5 of the 6 extraocular muscles which form an interlocking tendinous ring made of fibrous connective tissue. The 5 muscles include the lateral, medial, superior and inferior rectus, and the superior oblique muscle. This common tendinous ring is known as the annulus of Zinn and surrounds the entry of the optic nerve. The remaining sixth muscle is the inferior oblique muscle and is separate from the aforementioned tendinous ring due to its distinct point of origin. <ref name=''21482859''/>.

===Eyelids===

The eyelids are upper and lower folds of skin functioning as a barrier protecting the anterior surface of the eye from direct local injury. Eyelids also regulate light exposure, distribute precorneal tear film over the corneal surface when blinking and are involved in functions involving tear flow <ref><pubmed>1993591</pubmed></ref>.
No sign of eyelid fold development is evident at week 5 however at this stage the lens pit begins to invaginate from the surface ectoderm <ref name=’’27124372’’><pubmed>27124372</pubmed></ref>. Week 6 initiates the timeline of eyelid development as small depressions emerge in the surface ectoderm both above and below the developing eye – these rapidly deepen to form the folds of the eyelids <ref name=‘’7364662’’><pubmed>7364662</pubmed></ref>. The lower eyelid fold develops first and, by the end of week 6, the lower fold is more distinct than the upper eyelid fold <ref><pubmed>21416630</pubmed></ref>. Week 7 marks the point at which both the upper and lower folds are distinctly developed and during this stage, the upper lid assumes its more dominant role <ref name=’’27124372’’/>. The eyelid is not fully closed - there is a gap between the folds and the cornea is slightly visible – they eventually undergo fusion in week 8 <ref name=’’27124372’’/>.

===Lacrimal Glands===

The lacrimal glands are exocrine glands located in the upper lateral region of each eye orbit which secrete the aqueous potion of the tear film. This film is continuously secreted and functions to clean and protect the external surface of the eye, keeping the environment constantly moist and preventing possible injury from dust and other particles <ref><pubmed>17001201</ref>.
Lacrimal gland morphogenesis is identified in three stages.

* The first is the presumptive glandular stage. This stage involves the thickening of the conjunctival superior fornix epithelium and the condensing of the surrounding mesenchyme <ref name=’’14635806’’><pubmed>14635806</pubmed></ref>.

* The second is the bud stage. This stage is considered the initial sign of glandular formation due to the development of nodular structures and lumina within epithelia buds <ref name=’’14635806’’/>.

* The third is the glandular maturity stage (week 9-16). In this stage, the lacrimal gland begins to morphologically mirror the adult gland <ref name=’’14635806’’/>.

==Signalling pathways and transcription factors involved throughout eye development==

===Eye field development===

Many signalling pathways and transcription factors are involved in the development of the eye field (which forms in addition to the telencephalon and diencephalon as part of division of the anterior neural plate). Eye progenitor cells are guided into the eye field region by fibroblast growth factor, bone morphogenetic protein and Wnt-signalling pathways <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>. Additionally, interactions between canonical and non-canonical Wnt-signalling have been shown to maintain the eye field border <ref name=’’16413771’><pubmed>16413771</pubmed></ref>.

The cells of the eye field express eye field transcription factors, some of which include Rx1/Rax, Pax6, Lhx2, Six3 and Otx2. Six3, Pax6, Otx2 and Rx1 specify retinal lineage and regulate progenitor cell movement to guide them to their correct locations <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>. Six3 also partly mediates Wnt-signalling repression, allowing for the development of the optic vesicles from the eye field <ref name=’’23684892 ’’><pubmed>23684892 </pubmed></ref>. Lhx2 maintains optic lineage in eye progenitor cells and suppresses the potential for differentiation towards different fates <ref name=’’23595746’’><pubmed>23595746</pubmed></ref>.

===Eye field division and progression to optic cup===

TGF-β, FGF and Shh family factors secreted by the axial mesoderm underlying the eye field initiate its splitting into two bilateral, symmetric eye primordia <ref name=’’23684892 ’’><pubmed>23684892 </pubmed></ref>. These factors also regulate the expression of transcription factors Pax2, Pax6, Vax1 and Vax2, thereby establishing the boundaries and patterning the proxiodistal and ventronasal axes of the optic vesicles <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>.

Despite the close relationship between cellular proliferation and morphogenesis, optic vesicle evagination does not appear to be mainly driven by proliferation <ref name=’’23684892 ’’><pubmed>23684892 </pubmed></ref>. Alternatively, it has been shown that retinoic acid has critical importance in optic vesicle evagination to form the optic cup <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>. Rx3 activity has also been observed to have involvement in optic vesicle evagination <ref name=’’23684892 ’’><pubmed>23684892 </pubmed></ref>.

===From optic cup to developed eye===

Lens placode maturation and lens development is dependent on Pax6 expression and regulation. During placode formation bone morphogenetic protein and fibroblast growth factor signalling regulate Pax6. Within the presumptive lens ectoderm, Pax6 is regulated by Six3 and Meis. However, within the presumptive epithelium Pax6 is a regulating factor, regulating the expression of Sox2 and eventually Six3 once the lens placode is formed <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>.

Meanwhile, in the primordial retina retinal progenitor cells become retinal ganglion cells through the expression of the basic helix-loop-helix transcription factor ath5 (which is regulated by Hh and Fgf signalling. The amacrine, horizontal and bipolar cells of the retina are generated by a variety of transcription factors, some of which include Pax6, Six3 and Foxn4 <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>. Crx and Otx2 positive cells progress towards photoreceptor fates and are further developed into rods and cones based on specific transcription factor expression (TRβ2 and RxRγ expression is required for cones, where as Nrl, Nr2e3 and Ascl1 expression is required for rods) <ref name=’’20648062’’><pubmed>20648062</pubmed></ref>. The transcription factors required for the development of the retinal pigment epithelium include Mitf, Otx1/Otx2 and Pax6. TGF-β, FGF, BMP and Hh signalling from the surrounding mesenchyme have also been shown to help induce retinal pigment epithelium fate in progenitor cells <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>.

Within the choroid, the expression and regulation of many different factors and signalling pathways is required for the development of proper arterial-venous connections, allowing for the functional circulation of nutrients and oxygen throughout the eye. VEGF, bFGF, PDGF and PEDF (from the retinal pigment epithelium) drive the development and maturation of choroidal blood vessels. Vascular patterning is regulated by the interactions between VEGF and Delta-like 4 factors. Additionally, Notch signalling has been shown to have importance in the formation of capillary beds <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>.

===Eye formation in the absence of the retina===

The gene Rx is a key component in the formation of retinal structures. Studies have shown that mice lacking Rx function do not form optic sulci or optic vesicles and do not have retina-specific gene expression. There has been made studies in human, medaka, zebrafish and Xenopus which suggest that Rx genes are required for the formation of the vertebrate retina. It is also shown that in Rx-deficient mouse embryos the mature lens does not develop. This indicates that retinal cells are necessary for lens formation, and if the mouse is lacking Rx gene, then it will not display any retina-specific gene expression <ref name="PMC3104407"/>.

It is thought that signaling from the optic vesicle is important to activate the lens-specific gene and the formation of the lens placode. If there are no retinal cells generated, then the morphogenesis of the optic cup does not take place and the lens will not form. The study also showed that elimination of β-catenin expression in the head surface ectoderm in Rx-deficient embryos would develop a lens-like structure even though there were no optic vesicle/cup. Elimination of β-catenin lead to upregulation of Pax6, which is a gene that has a key role in lens formation. This indicates that the optic vesicle/cup might not be required for lens formation. The lens developed smaller than in wild type embryos, which means that the optic cup/vesicle might have an effect on a determination of the size of the lens. It could be that the developing optic vesicle/cup shields the developing lens placode from signals for other tissues that could disturb the lens formation <ref name="PMC3104407"/>.

It is not fully understood if the formation of the auxiliary eye structures is dependent on the development of the eyeball and its components, the retina and the lens. A study made my Eric C. Swindell and al. showed that auxiliary eye structures form even in the absence of retinal morphogenesis and retina-specific gene expression. This indicates that there are two separate developmental processes involved in the formation of the eye and its associated structures. In the absence of the retina and the lens, we still see specific gene expression in the surface ectoderm initiating the formation of auxiliary eye structures like eyelids and lacrimal glands <ref name="PMC3104407"/>.

==Current research==

===Iris epithelium cells as a potential source for regenerative medicine for retinal pigment epithelium degeneration===

The retinal pigment epithelium (RPE) is a monolayer of neural-crest-derived cells and is located between the photoreceptors and the choroid. There are many disorders that involve dysfunctional RPE and leads to retinal degenerative diseases. There is no treatment for these diseases, therefore, one of the most promising future therapy for RPE related disorders is to replace the cells of the dysfunctional RPE <ref name="PMC5565104><pubmed>PMC5565104</pubmed></ref>..

Studies have focused on the development and use of induced pluripotent stem cells (iPSC) for cell replacement therapy. It is possible to differentiate iPSC in vitro towards RPE cells and use them for experimental transplantation studies in animal models. But an alternative strategy for a retinal replacement is based on transdifferentiation (direct conversion) and involves transforming an adult somatic cell into another adult somatic cell. Use of overexpression of cell-lineage specific genes can convert one cell into another cell type and skip the pluripotent state. Iris epithelium (IE) cells might be able to be transdifferentiated into the RPE since both RPE and IE are neuro-epithelia and has a common embryological origin - they both derive from neuroectoderm of the developing optic cup <ref name="PMC5565104"/>.

A study made by Anna Bennis et al. <ref name="PMC5565104"/>. has shown that the canonical pathways for the most highly expressed genes of the IE and the RPE were very similar. Wnt signaling pathways has shown to be active in the IE but not in the RPE. The Wnt signaling pathway consists of a group of signal transduction pathways that has an influence on cell fate determination and cell proliferation during embryonic development. Activation of Wnt SP makes it possible to reprogram somatic cells (also retinal neurons) into iPSC and is important for the differentiation of pluripotent stem cells to RPE cells. The high expression of Wnt SP genes in the iE suggests that the IE has a multipotent character during life and therefore could be transformed into RPE cells used for RPE replacement <ref name="PMC5565104"/>.

==Animal Models==
The zebrafish species is used to investigate ocular development, function and disease due to having the same morphology as other vertebrates including humans. The advantages of zebrafish include: they are able to quickly reach their sexual maturity, they behaviour can be observed quite early on because of their rapid development and most importantly, their embryos are translucent. Zebrafish is also active during the day therefore their retina contains a large number of diverse cone subtypes in additions to rods. <ref name="Zebrafish"> Glass, A. S. & Dahm, R. (2003). The Zebrafish as a Model Organism for Eye Development. ''Opthalmic Research, 36''(1), 4-24. doi: 10.1159/000076105</ref>

[[File:Chokh.png|250px|thumb|left| '''Figure 11.''' Wild type zebrafish vs chokh/rx3 knockout. Morphological differences with the absence of eyes in the knockout.]]
Through studying zebrafish, it was found that that a mutation in ''chokh/rx3'' gene results in the absence of eyes during the earliest stages of development due to failure of the retinal progenitor cells. <ref name="chokh">Loosli, F., Staub, W., Finger-Baier, K. C., Ober, E. A., Verkade, H., Wittbrodt, J. & Baier, H. (2003). Loss of eyes in zebrafish caused by mutation of chokh/rx3. ''EMBO Reports, 4''(9), 894-899. doi: 10.1038/sj.embor.embor919 </ref>. Optical vesicle is turned inside out and the neuronal differentiation is blocked. In this study, they have found that the DNA-binding homeodomain and the the entire C-terminal portion led to a nonsense mutation that resulted to complete loss of function in the eye. It was concluded that the gene ''chokh/rx3'' is important for the developing optic primordia.

==Congenital Abnormalities==
Although quite rare, abnormalities can occur during the embryonic development that causes serious effects to the features of the eyes, its function as well as the further normal development after birth. These abnormalities can occur unilaterally or bilaterally and it is also common for most reported cases to have more than one type of eye abnormalities at a time. Thus, the estimated prevalence statistics listed in the table can overlap.

{| class="wikitable"
! style="background:#f4a941" | Congenital Anomalies
! style="background:#f4a941" | Description
! style="background:#f4a941" | Epidemiology
|-
| Anopthalmia || The absence of the eyes.
| rowspan="2" | Prevalence: Anophthalmia-Microphthalmia Syndrome was estimated to be 5.3 per 100 000 cases <ref name="Anophthalmia">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: [[http://www.orpha.net/consor/cgi-bin/index.php]] </ref>
Cause: SOX2 gene mutation <ref name="SOX2 Gene"> Mauri, L., Franzoni, A., Scarcello, M.,
Sala, S., Garavelli, L. Modugno, A., ... Penco, S. (2015). SOX2, OTX2 and PAX6 analysis in subjects with anophthalmia and microphthalmia. ''European Journal of Medical Genetics, 58'', 66-70. doi: 10.1016/j.ejmg.2014.12.005 </ref>
|-
| Microphtalmia || Abnormal reduction in size of the eyeballs.
|-
| Keratoglobus || Structural abnormalities in the formation of the cornea - unknown cause - fixable through surgery<ref name="PMID23807384"><pubmed>23807384</pubmed></ref>
| Prevalence: understood to be a rare condition<ref name="PMID23807384"><pubmed>23807384</pubmed></ref>
|-
| Ptosis ('Lazy Eye')|| Structural abnormalities in the eyelid, can be congenital - specifically the failure of innervation of the oculomotor nerve for levator palpebrae superioris <ref name="PMID8759493"><pubmed>8759493</pubmed></ref> - fixable through surgery
| Prevalence: a relatively well known abnormality
|-
| Aphakia || Te absense of a lens in the eye, causing a loss of accommodation and hence far-sightedness. People with aphakia have relatively small pupils which are unable to dilate as much <ref name="PMID28913511"><pubmed>28913511</pubmed></ref>
| Prevalence: a rare congenital abnormality
|-
| Coloboma || A condition where parts of the eye is missing and failed to develop normally.
| Prevalence: Occular coloboma was estimated to be 8.0 per 100 000 cases <ref name="Anophthalmia">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: [[http://www.orpha.net/consor/cgi-bin/index.php]] </ref>
|-
| Aniridia || Complete or partial absence of the iris.
| Prevalence: Estimated to be 1.5 per 100 000 cases <ref name="Anophthalmia">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: [[http://www.orpha.net/consor/cgi-bin/index.php]] </ref>
|-
| Optic Nerve Hypoplasia || A condition where the optic nerves are underdeveloped.
| Prevalence: Reported to be the most common abnormality <ref name="The Optic Nerve Hypoplasia">Ryabets-Lienhard, A., Stewart, C., Borchert, M., & Geffner, M. E. (2016). The Optic Nerve Hypoplasia Spectrum - Review of the Literature and Clinical Guidelines. ''Advances in Pediatrics, 63'', 127-146. doi: 10.1016/j.yapd.2016.04.009 </ref>
*10.9 per 100 000 in United Kingdom
*17.3 per 100 000 cases in Sweden.
*6.3% of cases was reported in New Zealand
|-
|}

<gallery>

Anophthalmia.jpeg|'''Figure 8.''' Anopthalmia
Microphthalmia-500px.jpg| '''Figure 9.''' Microphthalmia
Opac_figure_7.jpg| '''Figure 10.''' Iris Coloboma
Opac figure 10.jpg| '''Figure 11.''' Partial Aniridia
</gallery>

==Future questions==
===Will it be possible to have eye transplants in the future?===
Lots of research has been done in making a whole-eye transplantation successful in order to finally cure blindness. Blindness is a worldwide problem and is currently untreatable due to the fact that retinal ganglion cells and the optic nerves do not regenerate. This can result from diseases including macular degeneration and end of stage glaucoma. The first successful eye transplantation was led by Stone and Cole in 1943<ref name="Return of Vision"> Stone, L. S. & Cole, C. H. (1943). Grafted Eyes of Young and Old Adult Salamanders (Amblystoma Punctatum) Showing Return of Vision. ''Yale Journal of Biology and Medicine, 15''(5), 735-754.2. PMCID: PMC2601300</ref> investigating 104 samples of the salamander species, ''Amblystoma Punctatum'', and one of its eyes were either implanted back into the same animal or it was completely transplanted to a new host. It was reported that circulation in the iris was re-established, retina was able to regenerate, a new optic nerve was connected to the brain through the optic chiasma and ocular movements were regained. Vision was reestablished by the second month. In a more recent study, in 2015, Li et al.<ref name="Structural Integrity"> Li, Y., Komatsu, C., Wang, B., Miller, M., Wang, H., van der Merwe, Y., Ho, L., Kostereva, N., Zhang, W., Xiao, B., Davidson, E., Solari, M., Steketee, M. B., Guo, S., Kagemann, L., Wollstein, G., Schuman, J., Chan, K., Gorantla, V. S., Washington, K. M. (2015). Abstract 112: Evaluation of Viability, Structural Integrity and Functional Outcome after Whole Eye Transplantation. ''Plastic & Reconstructive Surgery, 135''(5), 82. "PMC2601300"</ref> investigated the feasibility of eye transplantation by observing the surviving 15 rat models out of the original 22. They were able to confirm the integrity and functional return of vision after whole-eye surgeries with the aid of advance techniques that are available today. The Ear and Eye Foundation of Pittsburgh<ref>'''Ear and Eye Foundation of Pittsburgh''': https://eyeandear.org/our-research/ophthalmology/the-whole-eye-transplant-project</ref> is an organization that is currently running a project with lead researchers to discover a way for the optic nerves to regenerate and to cure blindness by 2020.

===Will the bionic eye pass clinical trials in the next few years?===
[[File:BionicEye.jpg|250px|thumb|left| '''Figure 12.''' Bionic Eye Diagram]]

The bionic eye is an external visual device that has been in the making for the last several years. It hopes to bring back full vision through the aid of a pair of glasses with a camera attached to it, which then transmits high-frequency radio signals to the microchip implanted in the users' eye. These signals are converted into electrical impulses by the electrodes implanted in the chip, which then stimulates the retinal cells and passes through the optic nerve. Electrical impulses travels to the vision processing centres in the brain and these are then interpreted as an image. At the moment, users must learn to understand light flashes and visual patterns and convert them into images they can interpret. Current prototypes require the users to have a previously working eyes, which means their optic nerves must still be relatively healthy and their visual cortex must be developed. Patients who have suffered from retinitis pigmentosa and age-related macular degeneration would benefit this technology. Bionic Vision Australia<ref>'''Bionic Vision Australia''': http://bionicvision.org.au/about/research_plan</ref> is one of the leading organisations that are aiming to treat blindness and are set to perform clinical trials on two of the devices of the bionic eye implants soon. Their objectives are to develop strategies that can improve the affected visual pathway to the brain by stimulating the remaining working retinal cells and also develop safe surgical procedures.

==Glossary==

{| class="pretty table"
|-bgcolor = "DDCEF2"
|'''Term'''
|'''Definition'''
|-bgcolor="FAF5FF"
|'''Age-related macular degeneration'''||An eye disease with its onset usually after age 60 that can progressively destroy the macula, the central portion of the retina, impairing central vision.
|-
|'''Aqueous humour'''||A transparent fluid similar to plasma with low protein concentrations secreted by the ciliary epithelium.
|-
|'''Choroid'''||The pigmented vascular layer of the eye located between the retina and sclera.
|-
|'''Choroid fissure'''||A ventral groove formed by the invagination of the optic cup located at the bottom of the optic vesicle through which blood vessels enter the eye.
|-
|'''Ciliary body'''||The connection between the iris and choroid consisting of the ciliary muscle, ciliary processes and the ciliary ring. Alters the shape of the lens and ciliary epithelium in order to focus on an image.
|-
|'''Cornea'''||The transparent anterior part of the external coat of the eye covering the iris and pupil and continuous with the sclera.
|-
|'''Ectoderm||The outermost primary germ cell layer in the early embryo.
|-
|'''Endoderm||The innermost primary germ cell layer in the early embryo.
|-
|'''Ectodermal placode'''||A neurogenic placode consisting of an area of thickened epithelium in the embryonic head ectoderm layer that gives rise to neurons and other structures of the sensory system.
|-
|'''Extraocular muscles'''||Muscles controlling eye movement.
|-
|'''Fovea'''||A small depression in the retina where visual acuity is the highest.
|-
|'''Hyaloid vasculature'''||The temporary circulatory system in fetal eyes which spontaneously degenerate when the retinal blood vessels begin to develop.
|-
|'''Intraocular pressure'''||Fluid pressure inside the eye created through continued renewal of fluids.
|-
|'''Iris'''||The coloured muscular ring surrounding the pupil which manipulates the diameter and size of the pupil and controls the amount of light entering the eye.
|-
|'''Lens'''||The transparent biconvex structure posterior to the iris with the main function of focusing light onto the retina in order to form clear images of objects at various distances.
|-
|'''Lens pit'''||A pit-like depression in the fetal head where the lens develops.
|-
|'''Lens placode'''||The placode developing in the ectoderm overlying the optic vesicle, eventually becoming the lens of the eye.
|-
|'''Lens vesicle'''||The ectodermal invagination in the embryo formed opposite the optic cup and gives rise to the lens.
|-
|'''Lumina'''||the central cavity of a tubular structure.
|-
|'''Macula'''||An oval-shaped pigmented area where there is the largest density of cone cells and is involved in producing the sharpness of central vision.
|-
|'''Mesenchyme'''||Loosely organised embryonic connective tissue originating from the mesoderm.
|-
|'''Neural crest'''||A temporary group of embryonic ectodermal cells.
|-
|'''Neural retina'''||Refers to three layers of neural cells within the retina (photoreceptor cells, bipolar cells and ganglion cells).
|-
|'''Neural tube'''||A hollow tubular structure as a result of neural plate folding which later develops into the brain and spinal cord.
|-
|'''Neuroepithelium'''||Epithelium consisting of specialised cells which detect sensory triggers for reception of external stimuli.
|-
|'''Optic cup'''||A structure of the diencephalon formed after optic vesicle folding. This structure gives rise to the retina.
|-
|'''Optic groove'''||Two small grooves on each side of the developing forebrain in the neural folds. Also chiasmatic groove.
|-
|'''Optic nerve'''||Cranial nerve II which transmits impulses to the brain from visual information detected by the photoreceptive retina.
|-
|'''Optic stalk'''||Pair of slender embryonic structures that give rise to the optic nerve.
|-
|'''Optic vesicle'''||An evagination of each lateral all of the embryonic vertebrate forebrain from which the nervous structures of the eye develop.
|-
|'''Pupil'''||The central opening in the iris, allowing and regulating the entry of light into the eye.
|-
|'''Retina'''||The sensory membrane that forms the inner lining of the eye containing rods and cones with the main function of photoreception. Nerve impulses in response to visual information are transmitted to the brain via the optic nerve.
|-
|'''Retinitis Pigmentosa'''||A chronic hereditary eye disease characterized by breakdown and loss of cells in the retina leading to progressive visual loss.
|-
|'''Sclera'''||The dense, white, fibrous membrane that, along with the cornea, forms the external protective covering of the eye
|-
|'''Tear film'''||A layer of tears which spreads over the eye, ultimately maintaining the health of the ocular surface by making the external surface smooth and clear.

|}

{{Glossary}}

==References==

<references/>

==External links==

<pubmed>26956898</pubmed>

2017 Group Project 4

2017-10-26T00:41:54Z

Z3416557:

{{ANAT2341Project2017header}}

=Eye Development=

==Introduction==

The eye is a complex sensory structure which allows a variety of species to intake and process visual information from the world around us. Most structures forming the human eye are developed between the embryonic weeks 3 through 10, deriving primarily from ectoderm, neural crest cells and mesenchyme.

This project page will start with a description of the functional anatomy of the adult eye, continue with a description and timeline of the embryonic formation of important structures of the eye and finish with an examination of congenital abnormalities, current research and pending questions for the near future.

We hope that this page provides you with an enjoyable, comprehensive introduction to the embryology of the eye (we have aimed to keep it a 'reachable' page!)

==Anatomy of the Adult Eye==

To discuss the key anatomical components of the eye, we will break down the eye in parts<ref>Chen, J., 2011. Handbook of Visual Display Technology. Springer Berlin Heidelberg. Chapter 2.1</ref>:

'''Supporting Structures (Orbit, Extraoccular Muscles, Lacrimal Gland, Eyelid)'''
[[File:22292144 10208413540209536 722417340 o.jpg|250px|thumb|right| '''Figure 1.''' Layers of the Eyeball]]
The orbit consists of a framework of bones and connective tissue which provide structural support and protection to the sensitive human eye. 7 bones contribute to the orbit of the eye: frontal, lacrimal, sphenoid, zygomatic, ethmoid, maxillary, palatine. Several openings exist in the orbital structure, 2 key fissures are the superior orbital fissure and inferior orbital fissure and the posterior optic canal. These openings allow cranial nerves passageway.

A set of 6 extraoccular muscles allow for a strong voluntary control of the movement of the eye. These muscles include superior recuts, inferior rectus, lateral rectus, medial rectus, inferior oblique, superior oblique muscles. These muscles are some of the smallest in the human body and are designed to produce fast, controlled motion to focus on an object of interest.

The eyelid is the anterior covering of the eye, consisting of a thin fold of skin. It is controlled by the levitator palpabrae superioris muscle. Superio-laterally to the eyelid is the lacrimal gland, which serves to create a film of tear, an important component to keeping the anterior surface of the eye moist. The eyelid assists in this process by opening and closing, or blinking, which spreads the tear film across the surface of the eye. Debris caught in the tear film is excreted through the lacrimal duct which is located on the infero-medial surface of the eyelid.
[[File:22251179_10208414266827701_870733039_o.jpg|250px|thumb|right| '''Figure 2.''' Anterior Part of the Eye]]

'''Layers of the Eyeball (Sclera, Choroid, Retina)'''

The superficial layers of the eyeball is the sclera, a thick fibrous layer which becomes thicker as it extends posteriorly. The sclera is the visible as the white part of our eye. It's function is to provide structural stability to the eye and serves as attachment for some extraoccular insertions. Deep to the sclera is the choroid, a vascular network which provides nourishment to the layers of the eyeball and plays a large role in the growth of the eye. Deep to the choroid is the retina, a network of nerve fibers which transmit visual information. The retina contains 2 types of photoreceptors which convert visible light into nerve impulses. Rods work best in low light environments while cones work best in high light enthronements and detect colour and sharp detail.<ref>Curcio CA, Hendrickson AE. Organization and development of the primate photoreceptor mosaic. Prog Ret Ret. 1991;10:89–120.</ref>: The retina does not extend to the anterior part of the eyeball, unlike the sclera and choroid layers.

'''Anterior structure (Lens, Cornea, Pupil, Iris, Ciliary Body, Conjunctiva Anterior Chamber)'''

The most anterior component of the eyeball is the cornea, which is a multilayered avascular transparent structure who's major function to the refract light to assist image formation (contributes about 75% of total refraction). Continuous with cornea superiorly and inferiorly is the conjunctiva. Deep to the cornera is the iris, or the coloured ring visible in the eye. The iris consists of 2 muscles which act to enhance and diminish the size of the pupil, a hole in the middle of the iris allowing light to enter the eye. Deep to the pupil and iris is the lens, which is a transparent structure which contributes the other 25% of the eye's refractive power. The lens changes shape through accomodation controlled by the ciliary body muscles. The ciliary body is the anterior extension of the choroid. The function of the lens is to focus images by changing refractive power based on the position and depth of focal objects. In between the anterior surface of the lens and posterior surface of the cornea is the anterior chamber. This chamber is filled with aqueous humor supplied by the ciliary body, who's function is to provide nutrients to ocular structures and maintain intraocular pressure.
[[File:22251314_10208414283908128_862494115_o.jpg|250px|thumb|right| '''Figure 3.''' Posterior Part of the Eye]]

'''Posterior structure (Optic Nerve, Optic Disc, Macula, Fovea, Posterior Chamber)'''

In the posterior section of the retina is the macula, a central spot in which a high concentration of cone photoreceptors are found. The direct centre of the macula is called the fovea which contains solely cone photoreceptors. The fovea is only part of the eye which can conduct 'perfect' 20/20 vision. It has a high workload and hence a strong vascular supporting structure<ref><pubmed>6462623</pubmed></ref>:. The most posterior part of the eye is the optic nerve (along with the central retinal artery and central retinal vein), which is responsible for transporting nerve impulses to the cerebral cortex for processing. The opening of the optic nerve is called the optic disc, which contains no photoreceptors and is a blind spot of the eye. Between the posterior surface of the lens, the retina and the optic disc is the posterior chamber. The posterior chamber contains a vitreous humour, a jelly like substance with a high viscosity.

==Embryonic Contributions==

Eye development is a complex process. It involves the formation of the retina and the lens, which we together call the eyeball. It also involves the formation of auxiliary eye structures which are the eyelid, lacrimal gland, and cornea. The retina is formed from the neuroectoderm, the lens from the surface ectoderm and the auxiliary tissues are formed from the head surface ectoderm, neural crest cells and the head mesoderm <ref name="PMC3104407><pubmed>PMC3104407</pubmed></ref>.

[[File:Stage14 sem2cl.jpg|300px|thumb|right| '''Figure 4.''' Stage 14]]

{| class="wikitable"
! style="background:#f4a941" | Embryonic contributions
! style="background:#f4a941" | Eye component
|-
| Neuroectoderm of the forebrain || Retina, Posterior layers of the iris, The optic nerve
|-
| Surface ectoderm of the head || The lens of the eye, The corneal epithelium
|-
| Mesoderm between the neuroectoderm and the surface ectoderm || The fibrous and vascular coats of the eye
|-
| Neural crest cells || Choroid, Sclera, Corneal endothelium
|}

==Timeline of embryonic development==

{| class="wikitable"
! style="background:#f4a941" | WEEK
! style="background:#f4a941" | DEVELOPMENT
|-
| 3-4 || Eye fields, Optic vesicles
|-
| 5-6 || Optic Cup, Lens Vesicle, Choroid Fissure, Hyaloid Artery
|-
| 7-8 || Cornea, Anterior Chamber, Pupillary Membrane, Lens, Retina
|-
| 8-10 || Eyelids
|-
| 9-15 || Iris, Ciliary Body
|}

==Carnegie Stages==

Carnegie Stages are a system of 23 stages used to describe developmental events of the vertebrate embryo. At stage 10 we see early signs related to eye development. The table below is an made of knowledge from Anthony A. Person's article <ref><pubmed>7364662</pubmed></ref>.

{| class="pretty table"
|-bgcolor = "DDCEF2"
|'''Stage'''
|'''Events'''
|-bgcolor="FAF5FF"
|'''Stage 10 (22 days)'''
|The optic primordium has developed. Two small grooves develop on each side of the developing forebrain in the neural folds - this is the optic grooves. The optic placode has begun to develop, which is seen by a small thickening of the surface ectoderm lateral to the hindbrain.
|-
|'''Stage 11 (24 days)'''
|Optic vesicle begins to form from the optic groove.

[[File:Stage11 histology-optic pit.jpg|300px|'''Figure 1.''' Stage 11]]
|-bgcolor="FAF5FF"
|'''Stage 12 (26 days)'''
|The optic vesicles have extended from the forbrain to the surface ectoderm. The optic vesicle now lies close to the surface ectoderm.
|-
|'''Stage 13 (28 days)'''
| The optic vesicle interacts with the surface ectoderm and will induce this ectoderm to form the lens placode, which is the precursor of the lens. Optic evagination differentiation makes it possible to identiy optic parts of retina, future pigmented layer of retina and optic stalk.

[[File:Stage_13_image_060.jpg|300px|'''Figure 2.''' Stage 13]]
|-bgcolor="FAF5FF"
|'''Stage 14 (32 days)'''
| The lens placode is indented by the lens pit and is be cup-shaped.
|-
| '''Stage 15 (33 days)'''
| The lens pit will close and form a circle that separates from the surface ectoderm and becomes the lens vesicle. The lens vesicle and optic cub lie close to the surface ectoderm, which creates a slight elevation in the region of the eye.
|-bgcolor="FAF5FF"
| '''Stage 16 (37 days )'''
| The lens body has grown and now has a D-shaped lens cavity. First indication of the development of the eyelids visible as eyelid grooves above and below the eye.
|-
| '''Stage 17 - 19'''
| Retinal pigment is visible and the retinal fissure is almost closed. The eyes are still laterally placed but starts to take a more anterior position. The lower eyelid fold develops first and then the eyelid fold above the eye.
|-bgcolor="FAF5FF"
| '''Stage 18 (44 days)'''
| Mesenchyme invades the region between the lens epithelium and the surface ectoderm. The eyes have shifted to a more anterior position. The groove above and below the eyes are deeper but have not joined yet.
|-
| '''Stage 19 - 22'''
| The eyelid folds develop into the eyelids and the upper and the lower eyelids now meet at the outer canthus, which is the corner of the eye.

[[File:Stage 22 image 208.jpg|300px|'''Figure 3.''' Stage 22]]
|-bgcolor="FAF5FF"
| '''Stage 20 (51 days)'''
| The lens cavity is lost. The upper and lower lids meet laterally and medially. The eyelids now partly cover the eye. Lens suture begins to form.
|-
| '''Stage 23 (57 days)'''
| End of embryonic period. The face begins to look human. Eyelids closure is complete.
|-
|-bgcolor="FAF5FF"
|-
|}

==Development of the eye components==

===Introduction===

<html5media width=“480" height="360">https://www.youtube.com/embed/ghHDFWlfpoQ</html5media>

[[File:DevelopmentEye-PMC43029243.jpg|400px|thumb|right|'''Figure 5.''' Stages of lens formation in mouse embryos]]

The eye starts to develop at 22 days. The optic grooves (sulci) appears in the neural folds at the cranial end of the embryo. When the neural fold fuse to form the forebrain, the optic grooves will form '''optic vesicles'''. The optic vesicles are continuous cavities from the cavity of the forebrain and project from the wall of the forebrain and into the mesenchyme. The optic vesicle extends from the diencephalon and will come in contact with the surface ectoderm of the head. This induces the formation of a lens placode.

The surface ectoderm near the optic vesicles will thicken and form the '''lens placodes'''. The lens placodes will sink into the surface ectoderm and form '''lens pits'''. The edges of the lens pits will travel towards each other and fuse to form round '''lens vesicles''', which will later lose connection with the surface ectoderm. The optic vesicles do also keep developing - they will form double-walled '''optic cups''' which are connected to the brain by the '''optic stalk'''. The two layers of the optic cup will differentiate in different directions. The cells of the outer layer will produce melanin pigment and later become the '''pigmented retina'''. The cells of the inner layer of the optic cup will proliferate fast and develop glia, ganglion cells, interneurons and light-sensitive photoreceptor neurons. These cells are in the '''neural retina'''. The ganglion cells of the retina are neurons that send signals to the brain. The axons of the ganglion cells of the neural retina will grow in the wall of the optic stalk. The cavity in the optic nerve will start disappearing, and instead, the axons of the ganglion cells will form the '''optic nerve'''. The optic stalk is now the optic nerve <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>

The optic cups will fold inwards around the lens while the lens vesicles have grown inwards so they have fully lost their connection with the surface ectoderm, which locates them in the cavities of the optic cups. The retinal fissures (linear grooves) will develop and cover the ventral surface of the optic cups and down to the optic stalk. The retinal fissures contain vascular mesenchyme and hyaloid blood vessels will develop here. The hyaloid artery supplies the structures in the eye with blood and the hyaloid vein will return the blood from these structures <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

'''Formation of the optic vesicle'''

It is a specific area of the neural ectoderm that will become the optic vesicle - this happens because of a group of transcription factors - Six3, Pax6, and Rx1. These transcription factors are expressed in the most anterior tip of the neural plate. This area will split into bilateral regions and form the optic vesicles. The Pax6 protein has shown to be especially important for the development of the lens and retina. This protein is important for photoreceptive cells in all phyla. Pax 6 is also present in the murine forebrain, hindbrain, and nasal placodes, but the eyes are most sensitive its absence <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

The sonic hedgehog gene is important for the separation of the single eye field into two fields. If this gene is inhibited, the eye field will not split which will result in cyclopia, a single eye in the center of the face <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

===Retina===

[[File:Bailey463.jpg|400px|thumb|right|'''Figure 6.''' Diagram of developing lens and optic cup]]

The retina is the essential component of the eye with the primary function of photoreception <ref><pubmed>7084144</pubmed></ref>. Formation of the retina begins with the specification of retinal cells in the anterior neuroectoderm. First morphological sign of eye development is the formation of two lateral grooves in the anterior neuroectoderm, which is called the optic sulci. The cells of the optic sulci will evaginate and form the optic vesicle. The distal portion of the optic vesicle will form the retina and the proximal will form the optic stalk <ref><pubmed>18675797 </pubmed></ref>. The retina develops from the walls of the optic cup, these walls develop into the two layers of the retina. The thin, outer layer of the optic cup will become the pigment layer of the retina and the thick, inner layer of the optic cup will differentiate into the neural retina. Forkhead transcription factors are regulating the proliferation and differentiation of the retinal precursor cells. During the embryonic and early fetal periods, the two layers of the retina are separated which makes an intraretinal space. The intraretinal space is derived from the cavity of the optic cup. The two layers of the retina will fuse and the intraretinal space will gradually disappear <ref name="Larsen'sHumanEmbryology">Schoenwolf, G.C., Bleyl, S.B., Brauer, P.R., Francis-West, P.H. & Philippa H. (2015). Larsen's human embryology (5th ed.). New York; Edinburgh: Churchill Livingstone.</ref>.

When the lens is developing the inner layer of the optic cup starts to proliferate and forms a thick neuroepithelium which will later differentiate into the neural retina. The neural retina contains photoreceptors and the cell bodies of neurons and is the light-sensitive region of the retina. The axons of the ganglion cells in the neural retina grow in the wall of the optic stalk and will form the optic nerve <ref name="Larsen'sHumanEmbryology">Schoenwolf, G.C., Bleyl, S.B., Brauer, P.R., Francis-West, P.H. & Philippa H. (2015). Larsen's human embryology (5th ed.). New York; Edinburgh: Churchill Livingstone.</ref>.

===Lens===

Human lens induction occurs at around 28 days and is completed around day 56. The surface ectoderm will thicken near the optic vesicle and create the lens placode and later form the lens vesicle <ref><pubmed>20171212 </pubmed></ref>. Lens cells come from ectoderm and differentiate into either lens fibers or the lens epithelium. The anterior monolayer of epithelial cells of the lens will create the lens epithelium, which makes the sheet of cuboidal epithelium covering the anterior surface of the lens. The posterior lens vesicle cells will produce the linear primary fibre cells aligned parallel to the optic axis. These fibres will create the lens mass and form the embryonic lens nucleus. The lens epithelial cells will keep proliferating and produce new cells which generate a secondary lens fiber cells. This rows of cell will form the outer shells and keep the lens growing throughout life. This makes the eye lens unique - it will have an addition of new cells inside the surrounding capsule all the time <ref><pubmed>25406393</pubmed></ref>.

===Ciliary Body===

The ciliary body is a muscular and secretory tissue and is located directly behind the lens. The ciliary body forms part of the anterior segment of the eye and is an important regulator of eye physiology and the vision. The ciliary body produces the aqueous fluid which fills the eyes and nourishes the lens and cornea - this aqueous fluid function to keep the eye in a pressurized and inflated state, which is important the vision.The ciliary body also synthesizes collagenIX and tenasin-C <ref><pubmed>17275804</pubmed></ref>.

The ciliary body extends from the iris root (anteriorly) to the ora serrata (posteriorly). It consist of ciliary muscles and ciliary processes. Each ciliary process (fold) is covered by a double-layered secretory epithelium; the outer pigmented and the inner unpigmented (closes to the lens). The epithelial layers of the ciliary body comes from the retina of the optic cup. We see two different ciliary body epithelium: the inner non-pigmented ciliary epithelium which is connected with the neural retina and the outer pigmented ciliary epithelium which is connected with the retinal pigmented epithelium. The epithelium of the iris is the further anterior extension. The epithelial layers are associated with a stroma containing the ciliary muscle. The ciliary muscle is complex, but can be divided into three portions; anterior, posterior and internal <ref><pubmed>12127103</pubmed></ref>.

In the chick eye development, we see the mesenchyme grow together on the margin of the optic cup and will form the stroma of the ciliary body and the iris, which is located more anteriorly. It is unknown how if the lens has a role in inducing the secretory ciliary body epithelium and the muscular iris epithelium <ref><pubmed>17275804</pubmed></ref>.

===Iris===

The iris is the circular, pigmented muscular portion of the eye with a central aperture that is the pupil. The main function of this round muscle is to manipulate pupil diameter as an adjustment to various conditions and to control the amount of light entering the eye <ref name=’’21413392’’><pubmed>21413392</pubmed></ref>. This is influenced by dilator pupillae (radial) and sphincter pupillae (constricting) muscles. Iris pigmentation is dependent on the abundance and distribution of certain types of melanin in the posterior epithelium of the iris (eumelanin and pheomelanin) <ref name=’’21413392’’/>.

The Iris develops at the end of the third month of development. The iris is a thin layer and derives from the anterior rim of the optic cup <ref><pubmed>22219630</pubmed></ref>. The iris is formed by the pigment-containing internal and external layers of the optic cup and by a layer of vascularised connective tissue which also contains the pupillary muscles. Internal layers of the optic cup form the non-pigmented iris parts whereas the external layers of the optic cup develop into the pigmented epithelial structures. <ref name=’’18168498’’><pubmed>18168498</pubmed></ref>. Iris stroma develops as a result of neural crest cell migration – within this stroma, the dilator and constrictor muscles develop from the neuroectoderm of the optic cup. In the anterior of the eye, the optic epithelium is non-neural and matures as ciliary body and iris epithelia <ref name=’’18168498’’/>.

===Cornea===

The cornea is the unique, transparent and avascular component located at the most anterior section of the eye. It is composed of five layers stemming from the 3 main layers of epithelium, stroma and endothelium:

* Corneal epithelium (most anteriorly) – consisting of multiple layers of cells which rest on a basement membrane.
* Bowman’s membrane – a clear, acellular homogenous layer. This layer is a modified portion of the stroma and has no regenerative capacity as a response to damage <ref name=''7084144''><pubmed>7084144</pubmed></ref>.
* Corneal stroma – largest portion of the retina consisting of collagenous tissue.
* Descemet’s membrane – a homogenous, elastic true basement layer with a regenerative capacity.
* Corneal endothelium – a single layer of cuboidal cells responsible for the maintenance of the dehydrative nature of corneal tissue. <ref name=''7084144''/>.

Corneal development involves interactions between ectoderm-derived tissues. More specifically, the corneal epithelium arises from interactions between the cranial ectoderm and optic vesicles derived from the neural ectoderm <ref name=''26310148''><pubmed>26310148</ref></pubmed>. The neural tube and the adjacent ectoderm give rise to the neural crest cells which are multipotent with a migratory capacity. These cells contribute to the formation of corneal epithelium and the stromal cells. Innervation of the cornea stroma and epithelium is derived from both the neural crest and the ectodermal placode <ref name=''26310148''/>. The endothelium is comprised of differentiated neural crest cells which contribute to the later formation of Descemet’s membrane <ref><pubmed>6511224</pubmed></ref>.

===Aqueous Chambers===

There are two aqueous chambers of the eye: anterior and poster. These chambers are filled with a plasma-like fluid called aqueous humour and is produced by the ciliary body and trabecular meshwork in 3 main stages: diffusion, ultrafiltration and active secretion <ref><pubmed>6763801</pubmed></ref>. The main function of this fluid is to maintain the intraocular pressure as well as provide structural integrity to the round shape of the eyeball. This structure also has a role in the immune response and provides nutrition to the avascular tissue (e.g., the cornea and lens). <ref><pubmed>21293732</pubmed></ref>.

The anterior chamber is defined as the developed space posterior to the cornea (between the cornea and the iris) and develops at the stage of differentiation of the mesodermal portion of the iris <ref name=’’18168498’’/>. The space defining the posterior chamber develops as the mesenchyme between the lens and the peripheral iris.

===Choroid and Sclera===

The choroid and sclera are both surround the eye and are located adjacent to each other (the choroid lines the inner portion of the sclera). The sclera is the outer, fibrous white layer of the eye which functions as a supportive wall of the eye ball and is continuous with the cornea <ref name=''7084144''/> . The heavy vasculature of the choroid provides a major supply of oxygen and nourishment to the retina <ref><pubmed>20044062</pubmed></ref>.
They are derived from interactions between the neural crest and mesoderm-derived mesenchyme. The sclera forms as a result of condensation of the mesenchyme outside the optic cup <ref><pubmed>1628748</pubmed></ref>.
The choroid arises from the mesenchyme surrounding the optic vesicle and the cranial neural crest cells. The first vasculature structures appear in the choroid during week 15 in the form of arterioles and venules; veins and arteries become distinguishable by week 22 <ref name=’’2199235’’><pubmed>2199235</pubmed></ref>.

===Extraocular muscles===

The extraocular muscles are responsible for eye movement within the eye orbit – a critical aspect of sight and communication. 6 main muscles contribute to eye movement. These include: superior rectus, inferior rectus, lateral rectus, medial rectus, superior oblique and inferior oblique.

The development of these muscles is dependent on interactions between the eye, its muscles and the neural crest. <ref name=''21482859''><pubmed>21482859</pubmed></ref>.
Somites supplied by cranial nerve III forms 5 of the 6 extraocular muscles which form an interlocking tendinous ring made of fibrous connective tissue. The 5 muscles include the lateral, medial, superior and inferior rectus, and the superior oblique muscle. This common tendinous ring is known as the annulus of Zinn and surrounds the entry of the optic nerve. The remaining sixth muscle is the inferior oblique muscle and is separate from the aforementioned tendinous ring due to its distinct point of origin. <ref name=''21482859''/>.

===Eyelids===

The eyelids are upper and lower folds of skin functioning as a barrier protecting the anterior surface of the eye from direct local injury. Eyelids also regulate light exposure, distribute precorneal tear film over the corneal surface when blinking and are involved in functions involving tear flow <ref><pubmed>1993591</pubmed></ref>.
No sign of eyelid fold development is evident at week 5 however at this stage the lens pit begins to invaginate from the surface ectoderm <ref name=’’27124372’’><pubmed>27124372</pubmed></ref>. Week 6 initiates the timeline of eyelid development as small depressions emerge in the surface ectoderm both above and below the developing eye – these rapidly deepen to form the folds of the eyelids <ref name=‘’7364662’’><pubmed>7364662</pubmed></ref>. The lower eyelid fold develops first and, by the end of week 6, the lower fold is more distinct than the upper eyelid fold <ref><pubmed>21416630</pubmed></ref>. Week 7 marks the point at which both the upper and lower folds are distinctly developed and during this stage, the upper lid assumes its more dominant role <ref name=’’27124372’’/>. The eyelid is not fully closed - there is a gap between the folds and the cornea is slightly visible – they eventually undergo fusion in week 8 <ref name=’’27124372’’/>.

===Lacrimal Glands===

The lacrimal glands are exocrine glands located in the upper lateral region of each eye orbit which secrete the aqueous potion of the tear film. This film is continuously secreted and functions to clean and protect the external surface of the eye, keeping the environment constantly moist and preventing possible injury from dust and other particles <ref><pubmed>17001201</ref>.
Lacrimal gland morphogenesis is identified in three stages.

* The first is the presumptive glandular stage. This stage involves the thickening of the conjunctival superior fornix epithelium and the condensing of the surrounding mesenchyme <ref name=’’14635806’’><pubmed>14635806</pubmed></ref>.

* The second is the bud stage. This stage is considered the initial sign of glandular formation due to the development of nodular structures and lumina within epithelia buds <ref name=’’14635806’’/>.

* The third is the glandular maturity stage (week 9-16). In this stage, the lacrimal gland begins to morphologically mirror the adult gland <ref name=’’14635806’’/>.

==Signalling pathways and transcription factors involved throughout eye development==

===Eye field development===

Many signalling pathways and transcription factors are involved in the development of the eye field (which forms in addition to the telencephalon and diencephalon as part of division of the anterior neural plate). Eye progenitor cells are guided into the eye field region by fibroblast growth factor, bone morphogenetic protein and Wnt-signalling pathways <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>. Additionally, interactions between canonical and non-canonical Wnt-signalling have been shown to maintain the eye field border <ref name=’’16413771’><pubmed>16413771</pubmed></ref>.

The cells of the eye field express eye field transcription factors, some of which include Rx1/Rax, Pax6, Lhx2, Six3 and Otx2. Six3, Pax6, Otx2 and Rx1 specify retinal lineage and regulate progenitor cell movement to guide them to their correct locations <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>. Six3 also partly mediates Wnt-signalling repression, allowing for the development of the optic vesicles from the eye field <ref name=’’23684892 ’’><pubmed>23684892 </pubmed></ref>. Lhx2 maintains optic lineage in eye progenitor cells and suppresses the potential for differentiation towards different fates <ref name=’’23595746’’><pubmed>23595746</pubmed></ref>.

===Eye field division and progression to optic cup===

TGF-β, FGF and Shh family factors secreted by the axial mesoderm underlying the eye field initiate its splitting into two bilateral, symmetric eye primordia <ref name=’’23684892 ’’><pubmed>23684892 </pubmed></ref>. These factors also regulate the expression of transcription factors Pax2, Pax6, Vax1 and Vax2, thereby establishing the boundaries and patterning the proxiodistal and ventronasal axes of the optic vesicles <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>.

Despite the close relationship between cellular proliferation and morphogenesis, optic vesicle evagination does not appear to be mainly driven by proliferation <ref name=’’23684892 ’’><pubmed>23684892 </pubmed></ref>. Alternatively, it has been shown that retinoic acid has critical importance in optic vesicle evagination to form the optic cup <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>. Rx3 activity has also been observed to have involvement in optic vesicle evagination <ref name=’’23684892 ’’><pubmed>23684892 </pubmed></ref>.

===From optic cup to developed eye===

Lens placode maturation and lens development is dependent on Pax6 expression and regulation. During placode formation bone morphogenetic protein and fibroblast growth factor signalling regulate Pax6. Within the presumptive lens ectoderm, Pax6 is regulated by Six3 and Meis. However, within the presumptive epithelium Pax6 is a regulating factor, regulating the expression of Sox2 and eventually Six3 once the lens placode is formed <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>.

Meanwhile, in the primordial retina retinal progenitor cells become retinal ganglion cells through the expression of the basic helix-loop-helix transcription factor ath5 (which is regulated by Hh and Fgf signalling. The amacrine, horizontal and bipolar cells of the retina are generated by a variety of transcription factors, some of which include Pax6, Six3 and Foxn4 <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>. Crx and Otx2 positive cells progress towards photoreceptor fates and are further developed into rods and cones based on specific transcription factor expression (TRβ2 and RxRγ expression is required for cones, where as Nrl, Nr2e3 and Ascl1 expression is required for rods) <ref name=’’20648062’’><pubmed>20648062</pubmed></ref>. The transcription factors required for the development of the retinal pigment epithelium include Mitf, Otx1/Otx2 and Pax6. TGF-β, FGF, BMP and Hh signalling from the surrounding mesenchyme have also been shown to help induce retinal pigment epithelium fate in progenitor cells <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>.

Within the choroid, the expression and regulation of many different factors and signalling pathways is required for the development of proper arterial-venous connections, allowing for the functional circulation of nutrients and oxygen throughout the eye. VEGF, bFGF, PDGF and PEDF (from the retinal pigment epithelium) drive the development and maturation of choroidal blood vessels. Vascular patterning is regulated by the interactions between VEGF and Delta-like 4 factors. Additionally, Notch signalling has been shown to have importance in the formation of capillary beds <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>.

===Eye formation in the absence of the retina===

The gene Rx is a key component in the formation of retinal structures. Studies have shown that mice lacking Rx function do not form optic sulci or optic vesicles and do not have retina-specific gene expression. There has been made studies in human, medaka, zebrafish and Xenopus which suggest that Rx genes are required for the formation of the vertebrate retina. It is also shown that in Rx-deficient mouse embryos the mature lens does not develop. This indicates that retinal cells are necessary for lens formation, and if the mouse is lacking Rx gene, then it will not display any retina-specific gene expression <ref name="PMC3104407"/>.

It is thought that signaling from the optic vesicle is important to activate the lens-specific gene and the formation of the lens placode. If there are no retinal cells generated, then the morphogenesis of the optic cup does not take place and the lens will not form. The study also showed that elimination of β-catenin expression in the head surface ectoderm in Rx-deficient embryos would develop a lens-like structure even though there were no optic vesicle/cup. Elimination of β-catenin lead to upregulation of Pax6, which is a gene that has a key role in lens formation. This indicates that the optic vesicle/cup might not be required for lens formation. The lens developed smaller than in wild type embryos, which means that the optic cup/vesicle might have an effect on a determination of the size of the lens. It could be that the developing optic vesicle/cup shields the developing lens placode from signals for other tissues that could disturb the lens formation <ref name="PMC3104407"/>.

It is not fully understood if the formation of the auxiliary eye structures is dependent on the development of the eyeball and its components, the retina and the lens. A study made my Eric C. Swindell and al. showed that auxiliary eye structures form even in the absence of retinal morphogenesis and retina-specific gene expression. This indicates that there are two separate developmental processes involved in the formation of the eye and its associated structures. In the absence of the retina and the lens, we still see specific gene expression in the surface ectoderm initiating the formation of auxiliary eye structures like eyelids and lacrimal glands <ref name="PMC3104407"/>.

==Current research==

===Iris epithelium cells as a potential source for regenerative medicine for retinal pigment epithelium degeneration===

The retinal pigment epithelium (RPE) is a monolayer of neural-crest-derived cells and is located between the photoreceptors and the choroid. There are many disorders that involve dysfunctional RPE and leads to retinal degenerative diseases. There is no treatment for these diseases, therefore, one of the most promising future therapy for RPE related disorders is to replace the cells of the dysfunctional RPE <ref name="PMC5565104><pubmed>PMC5565104</pubmed></ref>..

Studies have focused on the development and use of induced pluripotent stem cells (iPSC) for cell replacement therapy. It is possible to differentiate iPSC in vitro towards RPE cells and use them for experimental transplantation studies in animal models. But an alternative strategy for a retinal replacement is based on transdifferentiation (direct conversion) and involves transforming an adult somatic cell into another adult somatic cell. Use of overexpression of cell-lineage specific genes can convert one cell into another cell type and skip the pluripotent state. Iris epithelium (IE) cells might be able to be transdifferentiated into the RPE since both RPE and IE are neuro-epithelia and has a common embryological origin - they both derive from neuroectoderm of the developing optic cup <ref name="PMC5565104"/>.

A study made by Anna Bennis et al. <ref name="PMC5565104"/>. has shown that the canonical pathways for the most highly expressed genes of the IE and the RPE were very similar. Wnt signaling pathways has shown to be active in the IE but not in the RPE. The Wnt signaling pathway consists of a group of signal transduction pathways that has an influence on cell fate determination and cell proliferation during embryonic development. Activation of Wnt SP makes it possible to reprogram somatic cells (also retinal neurons) into iPSC and is important for the differentiation of pluripotent stem cells to RPE cells. The high expression of Wnt SP genes in the iE suggests that the IE has a multipotent character during life and therefore could be transformed into RPE cells used for RPE replacement <ref name="PMC5565104"/>.

==Animal Models==
The zebrafish species is used to investigate ocular development, function and disease due to having the same morphology as other vertebrates including humans. The advantages of zebrafish include: they are able to quickly reach their sexual maturity, they behaviour can be observed quite early on because of their rapid development and most importantly, their embryos are translucent. Zebrafish is also active during the day therefore their retina contains a large number of diverse cone subtypes in additions to rods. <ref name="Zebrafish"> Glass, A. S. & Dahm, R. (2003). The Zebrafish as a Model Organism for Eye Development. ''Opthalmic Research, 36''(1), 4-24. doi: 10.1159/000076105</ref>

[[File:Chokh.png|250px|thumb|left| '''Figure 11.''' Wild type zebrafish vs chokh/rx3 knockout. Morphological differences with the absence of eyes in the knockout.]]
Through studying zebrafish, it was found that that a mutation in ''chokh/rx3'' gene results in the absence of eyes during the earliest stages of development due to failure of the retinal progenitor cells. <ref name="chokh">Loosli, F., Staub, W., Finger-Baier, K. C., Ober, E. A., Verkade, H., Wittbrodt, J. & Baier, H. (2003). Loss of eyes in zebrafish caused by mutation of chokh/rx3. ''EMBO Reports, 4''(9), 894-899. doi: 10.1038/sj.embor.embor919 </ref>. Optical vesicle is turned inside out and the neuronal differentiation is blocked. In this study, they have found that the DNA-binding homeodomain and the the entire C-terminal portion led to a nonsense mutation that resulted to complete loss of function in the eye. It was concluded that the gene ''chokh/rx3'' is important for the developing optic primordia.

==Congenital Abnormalities==
Although quite rare, abnormalities can occur during the embryonic development that causes serious effects to the features of the eyes, its function as well as the further normal development after birth. These abnormalities can occur unilaterally or bilaterally and it is also common for most reported cases to have more than one type of eye abnormalities at a time. Thus, the estimated prevalence statistics listed in the table can overlap.

{| class="wikitable"
! style="background:#f4a941" | Congenital Anomalies
! style="background:#f4a941" | Description
! style="background:#f4a941" | Epidemiology
|-
| Anopthalmia || The absence of the eyes.
| rowspan="2" | Prevalence: Anophthalmia-Microphthalmia Syndrome was estimated to be 5.3 per 100 000 cases <ref name="Anophthalmia">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: [[http://www.orpha.net/consor/cgi-bin/index.php]] </ref>
Cause: SOX2 gene mutation <ref name="SOX2 Gene"> Mauri, L., Franzoni, A., Scarcello, M.,
Sala, S., Garavelli, L. Modugno, A., ... Penco, S. (2015). SOX2, OTX2 and PAX6 analysis in subjects with anophthalmia and microphthalmia. ''European Journal of Medical Genetics, 58'', 66-70. doi: 10.1016/j.ejmg.2014.12.005 </ref>
|-
| Microphtalmia || Abnormal reduction in size of the eyeballs.
|-
| Keratoglobus || Structural abnormalities in the formation of the cornea - unknown cause - fixable through surgery<ref name="PMID23807384"><pubmed>23807384</pubmed></ref>
| Prevalence: understood to be a rare condition<ref name="PMID23807384"><pubmed>23807384</pubmed></ref>
|-
| Ptosis ('Lazy Eye')|| Structural abnormalities in the eyelid, can be congenital - specifically the failure of innervation of the oculomotor nerve for levator palpebrae superioris <ref name="PMID8759493"><pubmed>8759493</pubmed></ref> - fixable through surgery
| Prevalence: a relatively well known abnormality
|-
| Aphakia || Te absense of a lens in the eye, causing a loss of accommodation and hence far-sightedness. People with aphakia have relatively small pupils which are unable to dilate as much <ref name="PMID28913511"><pubmed>28913511</pubmed></ref>
| Prevalence: a rare congenital abnormality
|-
| Coloboma || A condition where parts of the eye is missing and failed to develop normally.
| Prevalence: Occular coloboma was estimated to be 8.0 per 100 000 cases <ref name="Anophthalmia">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: [[http://www.orpha.net/consor/cgi-bin/index.php]] </ref>
|-
| Aniridia || Complete or partial absence of the iris.
| Prevalence: Estimated to be 1.5 per 100 000 cases <ref name="Anophthalmia">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: [[http://www.orpha.net/consor/cgi-bin/index.php]] </ref>
|-
| Optic Nerve Hypoplasia || A condition where the optic nerves are underdeveloped.
| Prevalence: Reported to be the most common abnormality <ref name="The Optic Nerve Hypoplasia">Ryabets-Lienhard, A., Stewart, C., Borchert, M., & Geffner, M. E. (2016). The Optic Nerve Hypoplasia Spectrum - Review of the Literature and Clinical Guidelines. ''Advances in Pediatrics, 63'', 127-146. doi: 10.1016/j.yapd.2016.04.009 </ref>
*10.9 per 100 000 in United Kingdom
*17.3 per 100 000 cases in Sweden.
*6.3% of cases was reported in New Zealand
|-
|}

<gallery>

Anophthalmia.jpeg|'''Figure 8.''' Anopthalmia
Microphthalmia-500px.jpg| '''Figure 9.''' Microphthalmia
Opac_figure_7.jpg| '''Figure 10.''' Iris Coloboma
Opac figure 10.jpg| '''Figure 11.''' Partial Aniridia
</gallery>

==Future questions==
===Will it be possible to have eye transplants in the future?===
Lots of research has been done in making a whole-eye transplantation successful in order to finally cure blindness. Blindness is a worldwide problem and is currently untreatable due to the fact that retinal ganglion cells and the optic nerves do not regenerate. This can result from diseases including macular degeneration and end of stage glaucoma. The first successful eye transplantation was led by Stone and Cole in 1943<ref name="Return of Vision"> Stone, L. S. & Cole, C. H. (1943). Grafted Eyes of Young and Old Adult Salamanders (Amblystoma Punctatum) Showing Return of Vision. ''Yale Journal of Biology and Medicine, 15''(5), 735-754.2. PMCID: PMC2601300</ref> investigating 104 samples of the salamander species, ''Amblystoma Punctatum'', and one of its eyes were either implanted back into the same animal or it was completely transplanted to a new host. It was reported that circulation in the iris was re-established, retina was able to regenerate, a new optic nerve was connected to the brain through the optic chiasma and ocular movements were regained. Vision was reestablished by the second month. In a more recent study, in 2015, Li et al.<ref name="Structural Integrity"> Li, Y., Komatsu, C., Wang, B., Miller, M., Wang, H., van der Merwe, Y., Ho, L., Kostereva, N., Zhang, W., Xiao, B., Davidson, E., Solari, M., Steketee, M. B., Guo, S., Kagemann, L., Wollstein, G., Schuman, J., Chan, K., Gorantla, V. S., Washington, K. M. (2015). Abstract 112: Evaluation of Viability, Structural Integrity and Functional Outcome after Whole Eye Transplantation. ''Plastic & Reconstructive Surgery, 135''(5), 82. "PMC2601300"</ref> investigated the feasibility of eye transplantation by observing the surviving 15 rat models out of the original 22. They were able to confirm the integrity and functional return of vision after whole-eye surgeries with the aid of advance techniques that are available today. The Ear and Eye Foundation of Pittsburgh<ref>'''Ear and Eye Foundation of Pittsburgh''': https://eyeandear.org/our-research/ophthalmology/the-whole-eye-transplant-project</ref> is an organization that is currently running a project with lead researchers to discover a way for the optic nerves to regenerate and to cure blindness by 2020.

===Will the bionic eye pass clinical trials in the next few years?===
[[File:BionicEye.jpg|250px|thumb|left| '''Figure 12.''' Bionic Eye Diagram]]

The bionic eye is an external visual device that has been in the making for the last several years. It hopes to bring back full vision through the aid of a pair of glasses with a camera attached to it, which then transmits high-frequency radio signals to the microchip implanted in the users' eye. These signals are converted into electrical impulses by the electrodes implanted in the chip, which then stimulates the retinal cells and passes through the optic nerve. Electrical impulses travels to the vision processing centres in the brain and these are then interpreted as an image. At the moment, users must learn to understand light flashes and visual patterns and convert them into images they can interpret. Current prototypes require the users to have a previously working eyes, which means their optic nerves must still be relatively healthy and their visual cortex must be developed. Patients who have suffered from retinitis pigmentosa and age-related macular degeneration would benefit this technology. Bionic Vision Australia<ref>'''Bionic Vision Australia''': http://bionicvision.org.au/about/research_plan</ref> is one of the leading organisations that are aiming to treat blindness and are set to perform clinical trials on two of the devices of the bionic eye implants soon. Their objectives are to develop strategies that can improve the affected visual pathway to the brain by stimulating the remaining working retinal cells and also develop safe surgical procedures.

==Glossary==

{| class="pretty table"
|-bgcolor = "DDCEF2"
|'''Term'''
|'''Definition'''
|-bgcolor="FAF5FF"
|'''Age-related macular degeneration'''||An eye disease with its onset usually after age 60 that can progressively destroy the macula, the central portion of the retina, impairing central vision.
|-
|'''Aqueous humour'''||A transparent fluid similar to plasma with low protein concentrations secreted by the ciliary epithelium.
|-
|'''Choroid'''||The pigmented vascular layer of the eye located between the retina and sclera.
|-
|'''Choroid fissure'''||A ventral groove formed by the invagination of the optic cup located at the bottom of the optic vesicle through which blood vessels enter the eye.
|-
|'''Ciliary body'''||The connection between the iris and choroid consisting of the ciliary muscle, ciliary processes and the ciliary ring. Alters the shape of the lens and ciliary epithelium in order to focus on an image.
|-
|'''Cornea'''||The transparent anterior part of the external coat of the eye covering the iris and pupil and continuous with the sclera.
|-
|'''Ectoderm||The outermost primary germ cell layer in the early embryo.
|-
|'''Endoderm||The innermost primary germ cell layer in the early embryo.
|-
|'''Ectodermal placode'''||A neurogenic placode consisting of an area of thickened epithelium in the embryonic head ectoderm layer that gives rise to neurons and other structures of the sensory system.
|-
|'''Extraocular muscles'''||Muscles controlling eye movement.
|-
|'''Fovea'''||A small depression in the retina where visual acuity is the highest.
|-
|'''Hyaloid vasculature'''||The temporary circulatory system in fetal eyes which spontaneously degenerate when the retinal blood vessels begin to develop.
|-
|'''Intraocular pressure'''||Fluid pressure inside the eye created through continued renewal of fluids.
|-
|'''Iris'''||The coloured muscular ring surrounding the pupil which manipulates the diameter and size of the pupil and controls the amount of light entering the eye.
|-
|'''Lens'''||The transparent biconvex structure posterior to the iris with the main function of focusing light onto the retina in order to form clear images of objects at various distances.
|-
|'''Lens pit'''||A pit-like depression in the fetal head where the lens develops.
|-
|'''Lens placode'''||The placode developing in the ectoderm overlying the optic vesicle, eventually becoming the lens of the eye.
|-
|'''Lens vesicle'''||The ectodermal invagination in the embryo formed opposite the optic cup and gives rise to the lens.
|-
|'''Lumina'''||the central cavity of a tubular structure.
|-
|'''Macula'''||An oval-shaped pigmented area where there is the largest density of cone cells and is involved in producing the sharpness of central vision.
|-
|'''Mesenchyme'''||Loosely organised embryonic connective tissue originating from the mesoderm.
|-
|'''Neural crest'''||A temporary group of embryonic ectodermal cells.
|-
|'''Neural retina'''||Refers to three layers of neural cells within the retina (photoreceptor cells, bipolar cells and ganglion cells).
|-
|'''Neural tube'''||A hollow tubular structure as a result of neural plate folding which later develops into the brain and spinal cord.
|-
|'''Neuroepithelium'''||Epithelium consisting of specialised cells which detect sensory triggers for reception of external stimuli.
|-
|'''Optic cup'''||A structure of the diencephalon formed after optic vesicle folding. This structure gives rise to the retina.
|-
|'''Optic groove'''||Two small grooves on each side of the developing forebrain in the neural folds. Also chiasmatic groove.
|-
|'''Optic nerve'''||Cranial nerve II which transmits impulses to the brain from visual information detected by the photoreceptive retina.
|-
|'''Optic stalk'''||Pair of slender embryonic structures that give rise to the optic nerve.
|-
|'''Optic vesicle'''||An evagination of each lateral all of the embryonic vertebrate forebrain from which the nervous structures of the eye develop.
|-
|'''Pupil'''||The central opening in the iris, allowing and regulating the entry of light into the eye.
|-
|'''Retina'''||The sensory membrane that forms the inner lining of the eye containing rods and cones with the main function of photoreception. Nerve impulses in response to visual information are transmitted to the brain via the optic nerve.
|-
|'''Retinitis Pigmentosa'''||A chronic hereditary eye disease characterized by breakdown and loss of cells in the retina leading to progressive visual loss.
|-
|'''Sclera'''||The dense, white, fibrous membrane that, along with the cornea, forms the external protective covering of the eye
|-
|'''Tear film'''||A layer of tears which spreads over the eye, ultimately maintaining the health of the ocular surface by making the external surface smooth and clear.

|}

{{Glossary}}

==References==

<references/>

==External links==

<pubmed>26956898</pubmed>

2017 Group Project 4

2017-10-26T00:09:54Z

Z3416557:

{{ANAT2341Project2017header}}

=Eye Development=

==Introduction==

==Anatomy of the Adult Eye==

The eye is a complex sensory structure which allows a variety of species to intake and process visual information from the world around us.

To discuss the key anatomical components of the eye, we will break down the eye in parts<ref>Chen, J., 2011. Handbook of Visual Display Technology. Springer Berlin Heidelberg. Chapter 2.1</ref>:

'''Supporting Structures (Orbit, Extraoccular Muscles, Lacrimal Gland, Eyelid)'''
[[File:22292144 10208413540209536 722417340 o.jpg|250px|thumb|right| '''Figure 1.''' Layers of the Eyeball]]
The orbit consists of a framework of bones and connective tissue which provide structural support and protection to the sensitive human eye. 7 bones contribute to the orbit of the eye: frontal, lacrimal, sphenoid, zygomatic, ethmoid, maxillary, palatine. Several openings exist in the orbital structure, 2 key fissures are the superior orbital fissure and inferior orbital fissure and the posterior optic canal. These openings allow cranial nerves passageway.

A set of 6 extraoccular muscles allow for a strong voluntary control of the movement of the eye. These muscles include superior recuts, inferior rectus, lateral rectus, medial rectus, inferior oblique, superior oblique muscles. These muscles are some of the smallest in the human body and are designed to produce fast, controlled motion to focus on an object of interest.

The eyelid is the anterior covering of the eye, consisting of a thin fold of skin. It is controlled by the levitator palpabrae superioris muscle. Superio-laterally to the eyelid is the lacrimal gland, which serves to create a film of tear, an important component to keeping the anterior surface of the eye moist. The eyelid assists in this process by opening and closing, or blinking, which spreads the tear film across the surface of the eye. Debris caught in the tear film is excreted through the lacrimal duct which is located on the infero-medial surface of the eyelid.
[[File:22251179_10208414266827701_870733039_o.jpg|250px|thumb|right| '''Figure 2.''' Anterior Part of the Eye]]

'''Layers of the Eyeball (Sclera, Choroid, Retina)'''

The superficial layers of the eyeball is the sclera, a thick fibrous layer which becomes thicker as it extends posteriorly. The sclera is the visible as the white part of our eye. It's function is to provide structural stability to the eye and serves as attachment for some extraoccular insertions. Deep to the sclera is the choroid, a vascular network which provides nourishment to the layers of the eyeball and plays a large role in the growth of the eye. Deep to the choroid is the retina, a network of nerve fibers which transmit visual information. The retina contains 2 types of photoreceptors which convert visible light into nerve impulses. Rods work best in low light environments while cones work best in high light enthronements and detect colour and sharp detail.<ref>Curcio CA, Hendrickson AE. Organization and development of the primate photoreceptor mosaic. Prog Ret Ret. 1991;10:89–120.</ref>: The retina does not extend to the anterior part of the eyeball, unlike the sclera and choroid layers.

'''Anterior structure (Lens, Cornea, Pupil, Iris, Ciliary Body, Conjunctiva Anterior Chamber)'''

The most anterior component of the eyeball is the cornea, which is a multilayered avascular transparent structure who's major function to the refract light to assist image formation (contributes about 75% of total refraction). Continuous with cornea superiorly and inferiorly is the conjunctiva. Deep to the cornera is the iris, or the coloured ring visible in the eye. The iris consists of 2 muscles which act to enhance and diminish the size of the pupil, a hole in the middle of the iris allowing light to enter the eye. Deep to the pupil and iris is the lens, which is a transparent structure which contributes the other 25% of the eye's refractive power. The lens changes shape through accomodation controlled by the ciliary body muscles. The ciliary body is the anterior extension of the choroid. The function of the lens is to focus images by changing refractive power based on the position and depth of focal objects. In between the anterior surface of the lens and posterior surface of the cornea is the anterior chamber. This chamber is filled with aqueous humor supplied by the ciliary body, who's function is to provide nutrients to ocular structures and maintain intraocular pressure.
[[File:22251314_10208414283908128_862494115_o.jpg|250px|thumb|right| '''Figure 3.''' Posterior Part of the Eye]]

'''Posterior structure (Optic Nerve, Optic Disc, Macula, Fovea, Posterior Chamber)'''

In the posterior section of the retina is the macula, a central spot in which a high concentration of cone photoreceptors are found. The direct centre of the macula is called the fovea which contains solely cone photoreceptors. The fovea is only part of the eye which can conduct 'perfect' 20/20 vision. It has a high workload and hence a strong vascular supporting structure<ref><pubmed>6462623</pubmed></ref>:. The most posterior part of the eye is the optic nerve (along with the central retinal artery and central retinal vein), which is responsible for transporting nerve impulses to the cerebral cortex for processing. The opening of the optic nerve is called the optic disc, which contains no photoreceptors and is a blind spot of the eye. Between the posterior surface of the lens, the retina and the optic disc is the posterior chamber. The posterior chamber contains a vitreous humour, a jelly like substance with a high viscosity.

==Embryonic Contributions==

Eye development is a complex process. It involves the formation of the retina and the lens, which we together call the eyeball. It also involves the formation of auxiliary eye structures which are the eyelid, lacrimal gland, and cornea. The retina is formed from the neuroectoderm, the lens from the surface ectoderm and the auxiliary tissues are formed from the head surface ectoderm, neural crest cells and the head mesoderm <ref name="PMC3104407><pubmed>PMC3104407</pubmed></ref>.

[[File:Stage14 sem2cl.jpg|300px|thumb|right| '''Figure 4.''' Stage 14]]

{| class="wikitable"
! style="background:#f4a941" | Embryonic contributions
! style="background:#f4a941" | Eye component
|-
| Neuroectoderm of the forebrain || Retina, Posterior layers of the iris, The optic nerve
|-
| Surface ectoderm of the head || The lens of the eye, The corneal epithelium
|-
| Mesoderm between the neuroectoderm and the surface ectoderm || The fibrous and vascular coats of the eye
|-
| Neural crest cells || Choroid, Sclera, Corneal endothelium
|}

==Timeline of embryonic development==

{| class="wikitable"
! style="background:#f4a941" | WEEK
! style="background:#f4a941" | DEVELOPMENT
|-
| 3-4 || Eye fields, Optic vesicles
|-
| 5-6 || Optic Cup, Lens Vesicle, Choroid Fissure, Hyaloid Artery
|-
| 7-8 || Cornea, Anterior Chamber, Pupillary Membrane, Lens, Retina
|-
| 8-10 || Eyelids
|-
| 9-15 || Iris, Ciliary Body
|}

==Carnegie Stages==

Carnegie Stages are a system of 23 stages used to describe developmental events of the vertebrate embryo. At stage 10 we see early signs related to eye development. The table below is an made of knowledge from Anthony A. Person's article <ref><pubmed>7364662</pubmed></ref>.

{| class="pretty table"
|-bgcolor = "DDCEF2"
|'''Stage'''
|'''Events'''
|-bgcolor="FAF5FF"
|'''Stage 10 (22 days)'''
|The optic primordium has developed. Two small grooves develop on each side of the developing forebrain in the neural folds - this is the optic grooves. The optic placode has begun to develop, which is seen by a small thickening of the surface ectoderm lateral to the hindbrain.
|-
|'''Stage 11 (24 days)'''
|Optic vesicle begins to form from the optic groove.

[[File:Stage11 histology-optic pit.jpg|300px|'''Figure 1.''' Stage 11]]
|-bgcolor="FAF5FF"
|'''Stage 12 (26 days)'''
|The optic vesicles have extended from the forbrain to the surface ectoderm. The optic vesicle now lies close to the surface ectoderm.
|-
|'''Stage 13 (28 days)'''
| The optic vesicle interacts with the surface ectoderm and will induce this ectoderm to form the lens placode, which is the precursor of the lens. Optic evagination differentiation makes it possible to identiy optic parts of retina, future pigmented layer of retina and optic stalk.

[[File:Stage_13_image_060.jpg|300px|'''Figure 2.''' Stage 13]]
|-bgcolor="FAF5FF"
|'''Stage 14 (32 days)'''
| The lens placode is indented by the lens pit and is be cup-shaped.
|-
| '''Stage 15 (33 days)'''
| The lens pit will close and form a circle that separates from the surface ectoderm and becomes the lens vesicle. The lens vesicle and optic cub lie close to the surface ectoderm, which creates a slight elevation in the region of the eye.
|-bgcolor="FAF5FF"
| '''Stage 16 (37 days )'''
| The lens body has grown and now has a D-shaped lens cavity. First indication of the development of the eyelids visible as eyelid grooves above and below the eye.
|-
| '''Stage 17 - 19'''
| Retinal pigment is visible and the retinal fissure is almost closed. The eyes are still laterally placed but starts to take a more anterior position. The lower eyelid fold develops first and then the eyelid fold above the eye.
|-bgcolor="FAF5FF"
| '''Stage 18 (44 days)'''
| Mesenchyme invades the region between the lens epithelium and the surface ectoderm. The eyes have shifted to a more anterior position. The groove above and below the eyes are deeper but have not joined yet.
|-
| '''Stage 19 - 22'''
| The eyelid folds develop into the eyelids and the upper and the lower eyelids now meet at the outer canthus, which is the corner of the eye.

[[File:Stage 22 image 208.jpg|300px|'''Figure 3.''' Stage 22]]
|-bgcolor="FAF5FF"
| '''Stage 20 (51 days)'''
| The lens cavity is lost. The upper and lower lids meet laterally and medially. The eyelids now partly cover the eye. Lens suture begins to form.
|-
| '''Stage 23 (57 days)'''
| End of embryonic period. The face begins to look human. Eyelids closure is complete.
|-
|-bgcolor="FAF5FF"
|-
|}

==Development of the eye components==

===Introduction===

<html5media width=“480" height="360">https://www.youtube.com/embed/ghHDFWlfpoQ</html5media>

[[File:DevelopmentEye-PMC43029243.jpg|400px|thumb|right|'''Figure 5.''' Stages of lens formation in mouse embryos]]

The eye starts to develop at 22 days. The optic grooves (sulci) appears in the neural folds at the cranial end of the embryo. When the neural fold fuse to form the forebrain, the optic grooves will form '''optic vesicles'''. The optic vesicles are continuous cavities from the cavity of the forebrain and project from the wall of the forebrain and into the mesenchyme. The optic vesicle extends from the diencephalon and will come in contact with the surface ectoderm of the head. This induces the formation of a lens placode.

The surface ectoderm near the optic vesicles will thicken and form the '''lens placodes'''. The lens placodes will sink into the surface ectoderm and form '''lens pits'''. The edges of the lens pits will travel towards each other and fuse to form round '''lens vesicles''', which will later lose connection with the surface ectoderm. The optic vesicles do also keep developing - they will form double-walled '''optic cups''' which are connected to the brain by the '''optic stalk'''. The two layers of the optic cup will differentiate in different directions. The cells of the outer layer will produce melanin pigment and later become the '''pigmented retina'''. The cells of the inner layer of the optic cup will proliferate fast and develop glia, ganglion cells, interneurons and light-sensitive photoreceptor neurons. These cells are in the '''neural retina'''. The ganglion cells of the retina are neurons that send signals to the brain. The axons of the ganglion cells of the neural retina will grow in the wall of the optic stalk. The cavity in the optic nerve will start disappearing, and instead, the axons of the ganglion cells will form the '''optic nerve'''. The optic stalk is now the optic nerve <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>

The optic cups will fold inwards around the lens while the lens vesicles have grown inwards so they have fully lost their connection with the surface ectoderm, which locates them in the cavities of the optic cups. The retinal fissures (linear grooves) will develop and cover the ventral surface of the optic cups and down to the optic stalk. The retinal fissures contain vascular mesenchyme and hyaloid blood vessels will develop here. The hyaloid artery supplies the structures in the eye with blood and the hyaloid vein will return the blood from these structures <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

'''Formation of the optic vesicle'''

It is a specific area of the neural ectoderm that will become the optic vesicle - this happens because of a group of transcription factors - Six3, Pax6, and Rx1. These transcription factors are expressed in the most anterior tip of the neural plate. This area will split into bilateral regions and form the optic vesicles. The Pax6 protein has shown to be especially important for the development of the lens and retina. This protein is important for photoreceptive cells in all phyla. Pax 6 is also present in the murine forebrain, hindbrain, and nasal placodes, but the eyes are most sensitive its absence <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

The sonic hedgehog gene is important for the separation of the single eye field into two fields. If this gene is inhibited, the eye field will not split which will result in cyclopia, a single eye in the center of the face <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

===Retina===

[[File:Bailey463.jpg|400px|thumb|right|'''Figure 6.''' Diagram of developing lens and optic cup]]

The retina is the essential component of the eye with the primary function of photoreception <ref><pubmed>7084144</pubmed></ref>. Formation of the retina begins with the specification of retinal cells in the anterior neuroectoderm. First morphological sign of eye development is the formation of two lateral grooves in the anterior neuroectoderm, which is called the optic sulci. The cells of the optic sulci will evaginate and form the optic vesicle. The distal portion of the optic vesicle will form the retina and the proximal will form the optic stalk <ref><pubmed>18675797 </pubmed></ref>. The retina develops from the walls of the optic cup, these walls develop into the two layers of the retina. The thin, outer layer of the optic cup will become the pigment layer of the retina and the thick, inner layer of the optic cup will differentiate into the neural retina. Forkhead transcription factors are regulating the proliferation and differentiation of the retinal precursor cells. During the embryonic and early fetal periods, the two layers of the retina are separated which makes an intraretinal space. The intraretinal space is derived from the cavity of the optic cup. The two layers of the retina will fuse and the intraretinal space will gradually disappear <ref name="Larsen'sHumanEmbryology">Schoenwolf, G.C., Bleyl, S.B., Brauer, P.R., Francis-West, P.H. & Philippa H. (2015). Larsen's human embryology (5th ed.). New York; Edinburgh: Churchill Livingstone.</ref>.

When the lens is developing the inner layer of the optic cup starts to proliferate and forms a thick neuroepithelium which will later differentiate into the neural retina. The neural retina contains photoreceptors and the cell bodies of neurons and is the light-sensitive region of the retina. The axons of the ganglion cells in the neural retina grow in the wall of the optic stalk and will form the optic nerve <ref name="Larsen'sHumanEmbryology">Schoenwolf, G.C., Bleyl, S.B., Brauer, P.R., Francis-West, P.H. & Philippa H. (2015). Larsen's human embryology (5th ed.). New York; Edinburgh: Churchill Livingstone.</ref>.

===Lens===

Human lens induction occurs at around 28 days and is completed around day 56. The surface ectoderm will thicken near the optic vesicle and create the lens placode and later form the lens vesicle <ref><pubmed>20171212 </pubmed></ref>. Lens cells come from ectoderm and differentiate into either lens fibers or the lens epithelium. The anterior monolayer of epithelial cells of the lens will create the lens epithelium, which makes the sheet of cuboidal epithelium covering the anterior surface of the lens. The posterior lens vesicle cells will produce the linear primary fibre cells aligned parallel to the optic axis. These fibres will create the lens mass and form the embryonic lens nucleus. The lens epithelial cells will keep proliferating and produce new cells which generate a secondary lens fiber cells. This rows of cell will form the outer shells and keep the lens growing throughout life. This makes the eye lens unique - it will have an addition of new cells inside the surrounding capsule all the time <ref><pubmed>25406393</pubmed></ref>.

===Ciliary Body===

The ciliary body is a muscular and secretory tissue and is located directly behind the lens. The ciliary body forms part of the anterior segment of the eye and is an important regulator of eye physiology and the vision. The ciliary body produces the aqueous fluid which fills the eyes and nourishes the lens and cornea - this aqueous fluid function to keep the eye in a pressurized and inflated state, which is important the vision.The ciliary body also synthesizes collagenIX and tenasin-C <ref><pubmed>17275804</pubmed></ref>.

The ciliary body extends from the iris root (anteriorly) to the ora serrata (posteriorly). It consist of ciliary muscles and ciliary processes. Each ciliary process (fold) is covered by a double-layered secretory epithelium; the outer pigmented and the inner unpigmented (closes to the lens). The epithelial layers of the ciliary body comes from the retina of the optic cup. We see two different ciliary body epithelium: the inner non-pigmented ciliary epithelium which is connected with the neural retina and the outer pigmented ciliary epithelium which is connected with the retinal pigmented epithelium. The epithelium of the iris is the further anterior extension. The epithelial layers are associated with a stroma containing the ciliary muscle. The ciliary muscle is complex, but can be divided into three portions; anterior, posterior and internal <ref><pubmed>12127103</pubmed></ref>.

In the chick eye development, we see the mesenchyme grow together on the margin of the optic cup and will form the stroma of the ciliary body and the iris, which is located more anteriorly. It is unknown how if the lens has a role in inducing the secretory ciliary body epithelium and the muscular iris epithelium <ref><pubmed>17275804</pubmed></ref>.

===Iris===

The iris is the circular, pigmented muscular portion of the eye with a central aperture that is the pupil. The main function of this round muscle is to manipulate pupil diameter as an adjustment to various conditions and to control the amount of light entering the eye <ref name=’’21413392’’><pubmed>21413392</pubmed></ref>. This is influenced by dilator pupillae (radial) and sphincter pupillae (constricting) muscles. Iris pigmentation is dependent on the abundance and distribution of certain types of melanin in the posterior epithelium of the iris (eumelanin and pheomelanin) <ref name=’’21413392’’/>.

The Iris develops at the end of the third month of development. The iris is a thin layer and derives from the anterior rim of the optic cup <ref><pubmed>22219630</pubmed></ref>. The iris is formed by the pigment-containing internal and external layers of the optic cup and by a layer of vascularised connective tissue which also contains the pupillary muscles. Internal layers of the optic cup form the non-pigmented iris parts whereas the external layers of the optic cup develop into the pigmented epithelial structures. <ref name=’’18168498’’><pubmed>18168498</pubmed></ref>. Iris stroma develops as a result of neural crest cell migration – within this stroma, the dilator and constrictor muscles develop from the neuroectoderm of the optic cup. In the anterior of the eye, the optic epithelium is non-neural and matures as ciliary body and iris epithelia <ref name=’’18168498’’/>.

===Cornea===

The cornea is the unique, transparent and avascular component located at the most anterior section of the eye. It is composed of five layers stemming from the 3 main layers of epithelium, stroma and endothelium:

* Corneal epithelium (most anteriorly) – consisting of multiple layers of cells which rest on a basement membrane.
* Bowman’s membrane – a clear, acellular homogenous layer. This layer is a modified portion of the stroma and has no regenerative capacity as a response to damage <ref name=''7084144''><pubmed>7084144</pubmed></ref>.
* Corneal stroma – largest portion of the retina consisting of collagenous tissue.
* Descemet’s membrane – a homogenous, elastic true basement layer with a regenerative capacity.
* Corneal endothelium – a single layer of cuboidal cells responsible for the maintenance of the dehydrative nature of corneal tissue. <ref name=''7084144''/>.

Corneal development involves interactions between ectoderm-derived tissues. More specifically, the corneal epithelium arises from interactions between the cranial ectoderm and optic vesicles derived from the neural ectoderm <ref name=''26310148''><pubmed>26310148</ref></pubmed>. The neural tube and the adjacent ectoderm give rise to the neural crest cells which are multipotent with a migratory capacity. These cells contribute to the formation of corneal epithelium and the stromal cells. Innervation of the cornea stroma and epithelium is derived from both the neural crest and the ectodermal placode <ref name=''26310148''/>. The endothelium is comprised of differentiated neural crest cells which contribute to the later formation of Descemet’s membrane <ref><pubmed>6511224</pubmed></ref>.

===Aqueous Chambers===

There are two aqueous chambers of the eye: anterior and poster. These chambers are filled with a plasma-like fluid called aqueous humour and is produced by the ciliary body and trabecular meshwork in 3 main stages: diffusion, ultrafiltration and active secretion <ref><pubmed>6763801</pubmed></ref>. The main function of this fluid is to maintain the intraocular pressure as well as provide structural integrity to the round shape of the eyeball. This structure also has a role in the immune response and provides nutrition to the avascular tissue (e.g., the cornea and lens). <ref><pubmed>21293732</pubmed></ref>.

The anterior chamber is defined as the developed space posterior to the cornea (between the cornea and the iris) and develops at the stage of differentiation of the mesodermal portion of the iris <ref name=’’18168498’’/>. The space defining the posterior chamber develops as the mesenchyme between the lens and the peripheral iris.

===Choroid and Sclera===

The choroid and sclera are both surround the eye and are located adjacent to each other (the choroid lines the inner portion of the sclera). The sclera is the outer, fibrous white layer of the eye which functions as a supportive wall of the eye ball and is continuous with the cornea <ref name=''7084144''/> . The heavy vasculature of the choroid provides a major supply of oxygen and nourishment to the retina <ref><pubmed>20044062</pubmed></ref>.
They are derived from interactions between the neural crest and mesoderm-derived mesenchyme. The sclera forms as a result of condensation of the mesenchyme outside the optic cup <ref><pubmed>1628748</pubmed></ref>.
The choroid arises from the mesenchyme surrounding the optic vesicle and the cranial neural crest cells. The first vasculature structures appear in the choroid during week 15 in the form of arterioles and venules; veins and arteries become distinguishable by week 22 <ref name=’’2199235’’><pubmed>2199235</pubmed></ref>.

===Extraocular muscles===

The extraocular muscles are responsible for eye movement within the eye orbit – a critical aspect of sight and communication. 6 main muscles contribute to eye movement. These include: superior rectus, inferior rectus, lateral rectus, medial rectus, superior oblique and inferior oblique.

The development of these muscles is dependent on interactions between the eye, its muscles and the neural crest. <ref name=''21482859''><pubmed>21482859</pubmed></ref>.
Somites supplied by cranial nerve III forms 5 of the 6 extraocular muscles which form an interlocking tendinous ring made of fibrous connective tissue. The 5 muscles include the lateral, medial, superior and inferior rectus, and the superior oblique muscle. This common tendinous ring is known as the annulus of Zinn and surrounds the entry of the optic nerve. The remaining sixth muscle is the inferior oblique muscle and is separate from the aforementioned tendinous ring due to its distinct point of origin. <ref name=''21482859''/>.

===Eyelids===

The eyelids are upper and lower folds of skin functioning as a barrier protecting the anterior surface of the eye from direct local injury. Eyelids also regulate light exposure, distribute precorneal tear film over the corneal surface when blinking and are involved in functions involving tear flow <ref><pubmed>1993591</pubmed></ref>.
No sign of eyelid fold development is evident at week 5 however at this stage the lens pit begins to invaginate from the surface ectoderm <ref name=’’27124372’’><pubmed>27124372</pubmed></ref>. Week 6 initiates the timeline of eyelid development as small depressions emerge in the surface ectoderm both above and below the developing eye – these rapidly deepen to form the folds of the eyelids <ref name=‘’7364662’’><pubmed>7364662</pubmed></ref>. The lower eyelid fold develops first and, by the end of week 6, the lower fold is more distinct than the upper eyelid fold <ref><pubmed>21416630</pubmed></ref>. Week 7 marks the point at which both the upper and lower folds are distinctly developed and during this stage, the upper lid assumes its more dominant role <ref name=’’27124372’’/>. The eyelid is not fully closed - there is a gap between the folds and the cornea is slightly visible – they eventually undergo fusion in week 8 <ref name=’’27124372’’/>.

===Lacrimal Glands===

The lacrimal glands are exocrine glands located in the upper lateral region of each eye orbit which secrete the aqueous potion of the tear film. This film is continuously secreted and functions to clean and protect the external surface of the eye, keeping the environment constantly moist and preventing possible injury from dust and other particles <ref><pubmed>17001201</ref>.
Lacrimal gland morphogenesis is identified in three stages.

* The first is the presumptive glandular stage. This stage involves the thickening of the conjunctival superior fornix epithelium and the condensing of the surrounding mesenchyme <ref name=’’14635806’’><pubmed>14635806</pubmed></ref>.

* The second is the bud stage. This stage is considered the initial sign of glandular formation due to the development of nodular structures and lumina within epithelia buds <ref name=’’14635806’’/>.

* The third is the glandular maturity stage (week 9-16). In this stage, the lacrimal gland begins to morphologically mirror the adult gland <ref name=’’14635806’’/>.

==Signalling pathways and transcription factors involved throughout eye development==

===Eye field development===

Many signalling pathways and transcription factors are involved in the development of the eye field (which forms in addition to the telencephalon and diencephalon as part of division of the anterior neural plate). Eye progenitor cells are guided into the eye field region by fibroblast growth factor, bone morphogenetic protein and Wnt-signalling pathways <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>. Additionally, interactions between canonical and non-canonical Wnt-signalling have been shown to maintain the eye field border <ref name=’’16413771’><pubmed>16413771</pubmed></ref>.

The cells of the eye field express eye field transcription factors, some of which include Rx1/Rax, Pax6, Lhx2, Six3 and Otx2. Six3, Pax6, Otx2 and Rx1 specify retinal lineage and regulate progenitor cell movement to guide them to their correct locations <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>. Six3 also partly mediates Wnt-signalling repression, allowing for the development of the optic vesicles from the eye field <ref name=’’23684892 ’’><pubmed>23684892 </pubmed></ref>. Lhx2 maintains optic lineage in eye progenitor cells and suppresses the potential for differentiation towards different fates <ref name=’’23595746’’><pubmed>23595746</pubmed></ref>.

===Eye field division and progression to optic cup===

TGF-β, FGF and Shh family factors secreted by the axial mesoderm underlying the eye field initiate its splitting into two bilateral, symmetric eye primordia <ref name=’’23684892 ’’><pubmed>23684892 </pubmed></ref>. These factors also regulate the expression of transcription factors Pax2, Pax6, Vax1 and Vax2, thereby establishing the boundaries and patterning the proxiodistal and ventronasal axes of the optic vesicles <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>.

Despite the close relationship between cellular proliferation and morphogenesis, optic vesicle evagination does not appear to be mainly driven by proliferation <ref name=’’23684892 ’’><pubmed>23684892 </pubmed></ref>. Alternatively, it has been shown that retinoic acid has critical importance in optic vesicle evagination to form the optic cup <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>. Rx3 activity has also been observed to have involvement in optic vesicle evagination <ref name=’’23684892 ’’><pubmed>23684892 </pubmed></ref>.

===From optic cup to developed eye===

Lens placode maturation and lens development is dependent on Pax6 expression and regulation. During placode formation bone morphogenetic protein and fibroblast growth factor signalling regulate Pax6. Within the presumptive lens ectoderm, Pax6 is regulated by Six3 and Meis. However, within the presumptive epithelium Pax6 is a regulating factor, regulating the expression of Sox2 and eventually Six3 once the lens placode is formed <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>.

Meanwhile, in the primordial retina retinal progenitor cells become retinal ganglion cells through the expression of the basic helix-loop-helix transcription factor ath5 (which is regulated by Hh and Fgf signalling. The amacrine, horizontal and bipolar cells of the retina are generated by a variety of transcription factors, some of which include Pax6, Six3 and Foxn4 <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>. Crx and Otx2 positive cells progress towards photoreceptor fates and are further developed into rods and cones based on specific transcription factor expression (TRβ2 and RxRγ expression is required for cones, where as Nrl, Nr2e3 and Ascl1 expression is required for rods) <ref name=’’20648062’’><pubmed>20648062</pubmed></ref>. The transcription factors required for the development of the retinal pigment epithelium include Mitf, Otx1/Otx2 and Pax6. TGF-β, FGF, BMP and Hh signalling from the surrounding mesenchyme have also been shown to help induce retinal pigment epithelium fate in progenitor cells <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>.

Within the choroid, the expression and regulation of many different factors and signalling pathways is required for the development of proper arterial-venous connections, allowing for the functional circulation of nutrients and oxygen throughout the eye. VEGF, bFGF, PDGF and PEDF (from the retinal pigment epithelium) drive the development and maturation of choroidal blood vessels. Vascular patterning is regulated by the interactions between VEGF and Delta-like 4 factors. Additionally, Notch signalling has been shown to have importance in the formation of capillary beds <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>.

===Eye formation in the absence of the retina===

The gene Rx is a key component in the formation of retinal structures. Studies have shown that mice lacking Rx function do not form optic sulci or optic vesicles and do not have retina-specific gene expression. There has been made studies in human, medaka, zebrafish and Xenopus which suggest that Rx genes are required for the formation of the vertebrate retina. It is also shown that in Rx-deficient mouse embryos the mature lens does not develop. This indicates that retinal cells are necessary for lens formation, and if the mouse is lacking Rx gene, then it will not display any retina-specific gene expression <ref name="PMC3104407"/>.

It is thought that signaling from the optic vesicle is important to activate the lens-specific gene and the formation of the lens placode. If there are no retinal cells generated, then the morphogenesis of the optic cup does not take place and the lens will not form. The study also showed that elimination of β-catenin expression in the head surface ectoderm in Rx-deficient embryos would develop a lens-like structure even though there were no optic vesicle/cup. Elimination of β-catenin lead to upregulation of Pax6, which is a gene that has a key role in lens formation. This indicates that the optic vesicle/cup might not be required for lens formation. The lens developed smaller than in wild type embryos, which means that the optic cup/vesicle might have an effect on a determination of the size of the lens. It could be that the developing optic vesicle/cup shields the developing lens placode from signals for other tissues that could disturb the lens formation <ref name="PMC3104407"/>.

It is not fully understood if the formation of the auxiliary eye structures is dependent on the development of the eyeball and its components, the retina and the lens. A study made my Eric C. Swindell and al. showed that auxiliary eye structures form even in the absence of retinal morphogenesis and retina-specific gene expression. This indicates that there are two separate developmental processes involved in the formation of the eye and its associated structures. In the absence of the retina and the lens, we still see specific gene expression in the surface ectoderm initiating the formation of auxiliary eye structures like eyelids and lacrimal glands <ref name="PMC3104407"/>.

==Current research==

===Iris epithelium cells as a potential source for regenerative medicine for retinal pigment epithelium degeneration===

The retinal pigment epithelium (RPE) is a monolayer of neural-crest-derived cells and is located between the photoreceptors and the choroid. There are many disorders that involve dysfunctional RPE and leads to retinal degenerative diseases. There is no treatment for these diseases, therefore, one of the most promising future therapy for RPE related disorders is to replace the cells of the dysfunctional RPE <ref name="PMC5565104><pubmed>PMC5565104</pubmed></ref>..

Studies have focused on the development and use of induced pluripotent stem cells (iPSC) for cell replacement therapy. It is possible to differentiate iPSC in vitro towards RPE cells and use them for experimental transplantation studies in animal models. But an alternative strategy for a retinal replacement is based on transdifferentiation (direct conversion) and involves transforming an adult somatic cell into another adult somatic cell. Use of overexpression of cell-lineage specific genes can convert one cell into another cell type and skip the pluripotent state. Iris epithelium (IE) cells might be able to be transdifferentiated into the RPE since both RPE and IE are neuro-epithelia and has a common embryological origin - they both derive from neuroectoderm of the developing optic cup <ref name="PMC5565104"/>.

A study made by Anna Bennis et al. <ref name="PMC5565104"/>. has shown that the canonical pathways for the most highly expressed genes of the IE and the RPE were very similar. Wnt signaling pathways has shown to be active in the IE but not in the RPE. The Wnt signaling pathway consists of a group of signal transduction pathways that has an influence on cell fate determination and cell proliferation during embryonic development. Activation of Wnt SP makes it possible to reprogram somatic cells (also retinal neurons) into iPSC and is important for the differentiation of pluripotent stem cells to RPE cells. The high expression of Wnt SP genes in the iE suggests that the IE has a multipotent character during life and therefore could be transformed into RPE cells used for RPE replacement <ref name="PMC5565104"/>.

==Animal Models==

==Congenital Abnormalities==
Although quite rare, abnormalities can occur during the embryonic development that causes serious effects to the features of the eyes, its function as well as the further normal development after birth. These abnormalities can occur unilaterally or bilaterally and it is also common for most reported cases to have more than one type of eye abnormalities at a time. Thus, the estimated prevalence statistics listed in the table can overlap.

{| class="wikitable"
! style="background:#f4a941" | Congenital Anomalies
! style="background:#f4a941" | Description
! style="background:#f4a941" | Epidemiology
|-
| Anopthalmia || The absence of the eyes.
| rowspan="2" | Prevalence: Anophthalmia-Microphthalmia Syndrome was estimated to be 5.3 per 100 000 cases <ref name="Anophthalmia">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: [[http://www.orpha.net/consor/cgi-bin/index.php]] </ref>
Cause: SOX2 gene mutation <ref name="SOX2 Gene"> Mauri, L., Franzoni, A., Scarcello, M.,
Sala, S., Garavelli, L. Modugno, A., ... Penco, S. (2015). SOX2, OTX2 and PAX6 analysis in subjects with anophthalmia and microphthalmia. ''European Journal of Medical Genetics, 58'', 66-70. doi: 10.1016/j.ejmg.2014.12.005 </ref>
|-
| Microphtalmia || Abnormal reduction in size of the eyeballs.
|-
| Keratoglobus || Structural abnormalities in the formation of the cornea - unknown cause - fixable through surgery<ref name="PMID23807384"><pubmed>23807384</pubmed></ref>
| Prevalence: understood to be a rare condition<ref name="PMID23807384"><pubmed>23807384</pubmed></ref>
|-
| Ptosis ('Lazy Eye')|| Structural abnormalities in the eyelid, can be congenital - specifically the failure of innervation of the oculomotor nerve for levator palpebrae superioris <ref name="PMID8759493"><pubmed>8759493</pubmed></ref> - fixable through surgery
| Prevalence: a relatively well known abnormality
|-
| Aphakia || Te absense of a lens in the eye, causing a loss of accommodation and hence far-sightedness. People with aphakia have relatively small pupils which are unable to dilate as much <ref name="PMID28913511"><pubmed>28913511</pubmed></ref>
| Prevalence: a rare congenital abnormality
|-
| Coloboma || A condition where parts of the eye is missing and failed to develop normally.
| Prevalence: Occular coloboma was estimated to be 8.0 per 100 000 cases <ref name="Anophthalmia">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: [[http://www.orpha.net/consor/cgi-bin/index.php]] </ref>
|-
| Aniridia || Complete or partial absence of the iris.
| Prevalence: Estimated to be 1.5 per 100 000 cases <ref name="Anophthalmia">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: [[http://www.orpha.net/consor/cgi-bin/index.php]] </ref>
|-
| Optic Nerve Hypoplasia || A condition where the optic nerves are underdeveloped.
| Prevalence: Reported to be the most common abnormality <ref name="The Optic Nerve Hypoplasia">Ryabets-Lienhard, A., Stewart, C., Borchert, M., & Geffner, M. E. (2016). The Optic Nerve Hypoplasia Spectrum - Review of the Literature and Clinical Guidelines. ''Advances in Pediatrics, 63'', 127-146. doi: 10.1016/j.yapd.2016.04.009 </ref>
*10.9 per 100 000 in United Kingdom
*17.3 per 100 000 cases in Sweden.
*6.3% of cases was reported in New Zealand
|-
|}

<gallery>

Anophthalmia.jpeg|'''Figure 7.''' Anopthalmia
Microphthalmia-500px.jpg| '''Figure 8.''' Microphthalmia
Opac_figure_7.jpg| '''Figure 9.''' Iris Coloboma
Opac figure 10.jpg| '''Figure 10.''' Partial Aniridia
</gallery>

==Future questions==
===Will it be possible to have eye transplants in the future?===
Lots of research has been done in making a whole-eye transplantation successful in order to finally cure blindness. Blindness is a worldwide problem and is currently untreatable due to the fact that retinal ganglion cells and the optic nerves do not regenerate. This can result from diseases including macular degeneration and end of stage glaucoma. The first successful eye transplantation was led by Stone and Cole in 1943<ref name="Return of Vision"> Stone, L. S. & Cole, C. H. (1943). Grafted Eyes of Young and Old Adult Salamanders (Amblystoma Punctatum) Showing Return of Vision. ''Yale Journal of Biology and Medicine, 15''(5), 735-754.2. PMCID: PMC2601300</ref> investigating 104 samples of the salamander species, ''Amblystoma Punctatum'', and one of its eyes were either implanted back into the same animal or it was completely transplanted to a new host. It was reported that circulation in the iris was re-established, retina was able to regenerate, a new optic nerve was connected to the brain through the optic chiasma and ocular movements were regained. Vision was reestablished by the second month. In a more recent study, in 2015, Li et al.<ref name="Structural Integrity"> Li, Y., Komatsu, C., Wang, B., Miller, M., Wang, H., van der Merwe, Y., Ho, L., Kostereva, N., Zhang, W., Xiao, B., Davidson, E., Solari, M., Steketee, M. B., Guo, S., Kagemann, L., Wollstein, G., Schuman, J., Chan, K., Gorantla, V. S., Washington, K. M. (2015). Abstract 112: Evaluation of Viability, Structural Integrity and Functional Outcome after Whole Eye Transplantation. ''Plastic & Reconstructive Surgery, 135''(5), 82. "PMC2601300"</ref> investigated the feasibility of eye transplantation by observing the surviving 15 rat models out of the original 22. They were able to confirm the integrity and functional return of vision after whole-eye surgeries with the aid of advance techniques that are available today. The Ear and Eye Foundation of Pittsburgh<ref>'''Ear and Eye Foundation of Pittsburgh''': https://eyeandear.org/our-research/ophthalmology/the-whole-eye-transplant-project</ref> is an organization that is currently running a project with lead researchers to discover a way for the optic nerves to regenerate and to cure blindness by 2020.

===Will the bionic eye pass clinical trials in the next few years?===
The bionic eye is an external visual device that has been in the making for the last several years. It hopes to bring back full vision through the aid of a pair of glasses with a camera attached to it, which then transmits high-frequency radio signals to the microchip implanted in the users' eye. These signals are converted into electrical impulses by the electrodes implanted in the chip, which then stimulates the retinal cells and passes through the optic nerve. Electrical impulses travels to the vision processing centres in the brain and these are then interpreted as an image. At the moment, users must learn to understand light flashes and visual patterns and convert them into images they can interpret. Current prototypes require the users to have a previously working eyes, which means their optic nerves must still be relatively healthy and their visual cortex must be developed. Patients who have suffered from retinitis pigmentosa and age-related macular degeneration would benefit this technology. Bionic Vision Australia<ref>'''Bionic Vision Australia''': http://bionicvision.org.au/about/research_plan</ref> is one of the leading organisations that are aiming to treat blindness and are set to perform clinical trials on two of the devices of the bionic eye implants soon. Their objectives are to develop strategies that can improve the affected visual pathway to the brain by stimulating the remaining working retinal cells and also develop safe surgical procedures.

==Glossary==

{| class="pretty table"
|-bgcolor = "DDCEF2"
|'''Term'''
|'''Definition'''
|-bgcolor="FAF5FF"
|'''Age-related macular degeneration'''||An eye disease with its onset usually after age 60 that can progressively destroy the macula, the central portion of the retina, impairing central vision.
|-
|'''Aqueous humour'''||A transparent fluid similar to plasma with low protein concentrations secreted by the ciliary epithelium.
|-
|'''Choroid'''||The pigmented vascular layer of the eye located between the retina and sclera.
|-
|'''Choroid fissure'''||A ventral groove formed by the invagination of the optic cup located at the bottom of the optic vesicle through which blood vessels enter the eye.
|-
|'''Ciliary body'''||The connection between the iris and choroid consisting of the ciliary muscle, ciliary processes and the ciliary ring. Alters the shape of the lens and ciliary epithelium in order to focus on an image.
|-
|'''Cornea'''||The transparent anterior part of the external coat of the eye covering the iris and pupil and continuous with the sclera.
|-
|'''Ectoderm||The outermost primary germ cell layer in the early embryo.
|-
|'''Endoderm||The innermost primary germ cell layer in the early embryo.
|-
|'''Ectodermal placode'''||A neurogenic placode consisting of an area of thickened epithelium in the embryonic head ectoderm layer that gives rise to neurons and other structures of the sensory system.
|-
|'''Extraocular muscles'''||Muscles controlling eye movement.
|-
|'''Fovea'''||A small depression in the retina where visual acuity is the highest.
|-
|'''Hyaloid vasculature'''||The temporary circulatory system in fetal eyes which spontaneously degenerate when the retinal blood vessels begin to develop.
|-
|'''Intraocular pressure'''||Fluid pressure inside the eye created through continued renewal of fluids.
|-
|'''Iris'''||The coloured muscular ring surrounding the pupil which manipulates the diameter and size of the pupil and controls the amount of light entering the eye.
|-
|'''Lens'''||The transparent biconvex structure posterior to the iris with the main function of focusing light onto the retina in order to form clear images of objects at various distances.
|-
|'''Lens pit'''||A pit-like depression in the fetal head where the lens develops.
|-
|'''Lens placode'''||The placode developing in the ectoderm overlying the optic vesicle, eventually becoming the lens of the eye.
|-
|'''Lens vesicle'''||The ectodermal invagination in the embryo formed opposite the optic cup and gives rise to the lens.
|-
|'''Lumina'''||the central cavity of a tubular structure.
|-
|'''Macula'''||An oval-shaped pigmented area where there is the largest density of cone cells and is involved in producing the sharpness of central vision.
|-
|'''Mesenchyme'''||Loosely organised embryonic connective tissue originating from the mesoderm.
|-
|'''Neural crest'''||A temporary group of embryonic ectodermal cells.
|-
|'''Neural retina'''||Refers to three layers of neural cells within the retina (photoreceptor cells, bipolar cells and ganglion cells).
|-
|'''Neural tube'''||A hollow tubular structure as a result of neural plate folding which later develops into the brain and spinal cord.
|-
|'''Neuroepithelium'''||Epithelium consisting of specialised cells which detect sensory triggers for reception of external stimuli.
|-
|'''Optic cup'''||A structure of the diencephalon formed after optic vesicle folding. This structure gives rise to the retina.
|-
|'''Optic groove'''||Two small grooves on each side of the developing forebrain in the neural folds. Also chiasmatic groove.
|-
|'''Optic nerve'''||Cranial nerve II which transmits impulses to the brain from visual information detected by the photoreceptive retina.
|-
|'''Optic stalk'''||Pair of slender embryonic structures that give rise to the optic nerve.
|-
|'''Optic vesicle'''||An evagination of each lateral all of the embryonic vertebrate forebrain from which the nervous structures of the eye develop.
|-
|'''Pupil'''||The central opening in the iris, allowing and regulating the entry of light into the eye.
|-
|'''Retina'''||The sensory membrane that forms the inner lining of the eye containing rods and cones with the main function of photoreception. Nerve impulses in response to visual information are transmitted to the brain via the optic nerve.
|-
|'''Retinitis Pigmentosa'''||A chronic hereditary eye disease characterized by breakdown and loss of cells in the retina leading to progressive visual loss.
|-
|'''Sclera'''||The dense, white, fibrous membrane that, along with the cornea, forms the external protective covering of the eye
|-
|'''Tear film'''||A layer of tears which spreads over the eye, ultimately maintaining the health of the ocular surface by making the external surface smooth and clear.

|}

{{Glossary}}

==References==

<references/>

==External links==

<pubmed>26956898</pubmed>

2017 Group Project 4

2017-10-26T00:04:03Z

Z3416557:

{{ANAT2341Project2017header}}

=Eye Development=

==Introduction==

==Anatomy of the Adult Eye==

The eye is a complex sensory structure which allows a variety of species to intake and process visual information from the world around us.

To discuss the key anatomical components of the eye, we will break down the eye in parts<ref>Chen, J., 2011. Handbook of Visual Display Technology. Springer Berlin Heidelberg. Chapter 2.1</ref>:

'''Supporting Structures (Orbit, Extraoccular Muscles, Lacrimal Gland, Eyelid)'''
[[File:22292144 10208413540209536 722417340 o.jpg|250px|thumb|right| '''Figure 1.''' Layers of the Eyeball]]
The orbit of the eye consists of a framework of bones and connective tissue which provide structural support and protection to the sensitive human eye. 7 bones contribute to the orbit of the eye: frontal, lacrimal, sphenoid, zygomtatic, ethmoid, maxilary, palatine. Several openings exist in the orbital structure, 2 key fissures are the superior orbital fissure and inferior orbital fissure and the posterior optic canal. These openings allow crainial nerves passageway.

A set of 6 extraoccular muscles allow for a strong voluntary control of the movement of the eye. These muscles include superior recuts, inferior rectus, lateral rectus, medial rectus, inferior oblique, superior oblique muscles. These muscles are some of the smallest in the human body and are designed to produce fast, controlled motion to focus on an object of interest.

The eyelid is the anterior covering of the eye, consisting of a thin fold of skin. It is controlled by the levitator palpabrae superioris muscle. Superio-laterally to the eyelid is the lacrimal gland, which serves to create a film of tear, an important component to keeping the anterior surface of the eye moist. The eyelid assists in this process by opening and closing, or blinking, which spreads the tear film across the surface of the eye. Tear film and debris caught in the tear film are excreted through the lacrimal duct which is located on the infero-medial surface of the eyelid.
[[File:22251179_10208414266827701_870733039_o.jpg|250px|thumb|right| '''Figure 2.''' Anterior Part of the Eye]]

'''Layers of the Eyeball (Sclera, Choroid, Retina)'''

The superficial layers of the eyeball is the sclera, a thick fibrous layer which becomes thicker as it extends posteriorly. The sclera is the visible as the white part of our eye. It's function is to provide structural stability to the eye and serves as attachment for some extraoccular insertions. Deep to the sclera is the choroid, a vascular network which provides nourishment to the layers of the eyeball and plays a large role in the growth of the eye. Deep to the choroid is the retina, a network of nerve fibers which transmit visual information. The retina contains 2 types of photoreceptors which convert visible light into nerve impulses. Rods work best in low light environments while cones work best in high light enthronements and detect colour and sharp detail.<ref>Curcio CA, Hendrickson AE. Organization and development of the primate photoreceptor mosaic. Prog Ret Ret. 1991;10:89–120.</ref>: The retina does not extend to the anterior part of the eyeball, unlike the sclera and choroid layers.

'''Anterior structure (Lens, Cornea, Pupil, Iris, Ciliary Body, Conjunctiva Anterior Chamber)'''

The most anterior component of the eyeball is the cornea, which is a multilayered avascular transparent structure who's major function to the refract light to assist image formation (contributes about 75% of total refraction). Continuous with cornea superiorly and inferiorly is the conjunctiva. Deep to the cornera is the iris, or the coloured ring visible in the eye. The iris consists of 2 muscles which act to enhance and diminish the size of the pupil, a hole in the middle of the iris allowing light to enter the eye. Deep to the pupil and iris is the lens, which is a transparent structure which contributes the other 25% of the eye's refractive power. The lens changes shape through accomodation controlled by the ciliary body muscles. The ciliary body is the anterior extension of the choroid. The function of the lens is to focus images by changing refractive power based on the position and depth of focal objects. In between the anterior surface of the lens and posterior surface of the cornea is the anterior chamber. This chamber is filled with aqueous humor supplied by the ciliary body, who's function is to provide nutrients to ocular structures and maintain intraocular pressure.
[[File:22251314_10208414283908128_862494115_o.jpg|250px|thumb|right| '''Figure 3.''' Posterior Part of the Eye]]

'''Posterior structure (Optic Nerve, Optic Disc, Macula, Fovea, Posterior Chamber)'''

In the posterior section of the retina is the macula, a central spot in which a high concentration of cone photoreceptors are found. The direct centre of the macula is called the fovea which contains solely cone photoreceptors. The fovea is only part of the eye which can conduct 'perfect' 20/20 vision. It has a high workload and hence a strong vascular supporting structure<ref><pubmed>6462623</pubmed></ref>:. The most posterior part of the eye is the optic nerve (along with the central retinal artery and central retinal vein), which is responsible for transporting nerve impulses to the cerebral cortex for processing. The opening of the optic nerve is called the optic disc, which contains no photoreceptors and is a blind spot of the eye. Between the posterior surface of the lens, the retina and the optic disc is the posterior chamber. The posterior chamber contains a vitreous humour, a jelly like substance with a high viscosity.

==Embryonic Contributions==

Eye development is a complex process. It involves the formation of the retina and the lens, which we together call the eyeball. It also involves the formation of auxiliary eye structures which are the eyelid, lacrimal gland, and cornea. The retina is formed from the neuroectoderm, the lens from the surface ectoderm and the auxiliary tissues are formed from the head surface ectoderm, neural crest cells and the head mesoderm <ref name="PMC3104407><pubmed>PMC3104407</pubmed></ref>.

[[File:Stage14 sem2cl.jpg|300px|thumb|right| '''Figure 4.''' Stage 14]]

{| class="wikitable"
! style="background:#f4a941" | Embryonic contributions
! style="background:#f4a941" | Eye component
|-
| Neuroectoderm of the forebrain || Retina, Posterior layers of the iris, The optic nerve
|-
| Surface ectoderm of the head || The lens of the eye, The corneal epithelium
|-
| Mesoderm between the neuroectoderm and the surface ectoderm || The fibrous and vascular coats of the eye
|-
| Neural crest cells || Choroid, Sclera, Corneal endothelium
|}

==Timeline of embryonic development==

{| class="wikitable"
! style="background:#f4a941" | WEEK
! style="background:#f4a941" | DEVELOPMENT
|-
| 3-4 || Eye fields, Optic vesicles
|-
| 5-6 || Optic Cup, Lens Vesicle, Choroid Fissure, Hyaloid Artery
|-
| 7-8 || Cornea, Anterior Chamber, Pupillary Membrane, Lens, Retina
|-
| 8-10 || Eyelids
|-
| 9-15 || Iris, Ciliary Body
|}

==Carnegie Stages==

Carnegie Stages is a system of 23 stages used to describe developmental events of the vertebrate embryo. At stage 10 we see early signs related to eye development. The table below is an made of knowledge from Anthony A. Person's article <ref><pubmed>7364662</pubmed></ref>.

{| class="pretty table"
|-bgcolor = "DDCEF2"
|'''Stage'''
|'''Events'''
|-bgcolor="FAF5FF"
|'''Stage 10 (22 days)'''
|The optic primordium has developed. Two small grooves develop on each side of the developing forebrain in the neural folds - this is the optic grooves. The optic placode has begun to develop, which is seen by a small thickening of the surface ectoderm lateral to the hindbrain.
|-
|'''Stage 11 (24 days)'''
|Optic vesicle begins to form from the optic groove.

[[File:Stage11 histology-optic pit.jpg|300px|'''Figure 1.''' Stage 11]]
|-bgcolor="FAF5FF"
|'''Stage 12 (26 days)'''
|The optic vesicles have extended from the forbrain to the surface ectoderm. The optic vesicle now lies close to the surface ectoderm.
|-
|'''Stage 13 (28 days)'''
| The optic vesicle interacts with the surface ectoderm and will induce this ectoderm to form the lens placode, which is the precursor of the lens. Optic evagination differentiation makes it possible to identiy optic parts of retina, future pigmented layer of retina and optic stalk.

[[File:Stage_13_image_060.jpg|300px|'''Figure 2.''' Stage 13]]
|-bgcolor="FAF5FF"
|'''Stage 14 (32 days)'''
| The lens placode is indented by the lens pit and is be cup-shaped.
|-
| '''Stage 15 (33 days)'''
| The lens pit will close and form a circle that separates from the surface ectoderm and becomes the lens vesicle. The lens vesicle and optic cub lie close to the surface ectoderm, which creates a slight elevation in the region of the eye.
|-bgcolor="FAF5FF"
| '''Stage 16 (37 days )'''
| The lens body has grown and now has a D-shaped lens cavity. First indication of the development of the eyelids visible as eyelid grooves above and below the eye.
|-
| '''Stage 17 - 19'''
| Retinal pigment is visible and the retinal fissure is almost closed. The eyes are still laterally placed but starts to take a more anterior position. The lower eyelid fold develops first and then the eyelid fold above the eye.
|-bgcolor="FAF5FF"
| '''Stage 18 (44 days)'''
| Mesenchyme invades the region between the lens epithelium and the surface ectoderm. The eyes have shifted to a more anterior position. The groove above and below the eyes are deeper but have not joined yet.
|-
| '''Stage 19 - 22'''
| The eyelid folds develop into the eyelids and the upper and the lower eyelids now meet at the outer canthus, which is the corner of the eye.

[[File:Stage 22 image 208.jpg|300px|'''Figure 3.''' Stage 22]]
|-bgcolor="FAF5FF"
| '''Stage 20 (51 days)'''
| The lens cavity is lost. The upper and lower lids meet laterally and medially. The eyelids now partly cover the eye. Lens suture begins to form.
|-
| '''Stage 23 (57 days)'''
| End of embryonic period. The face begins to look human. Eyelids closure is complete.
|-
|-bgcolor="FAF5FF"
|-
|}

==Development of the eye components==

===Introduction===

<html5media width=“480" height="360">https://www.youtube.com/embed/ghHDFWlfpoQ</html5media>

[[File:DevelopmentEye-PMC43029243.jpg|400px|thumb|right|'''Figure 5.''' Stages of lens formation in mouse embryos]]

The eye starts to develop at 22 days. The optic grooves (sulci) appears in the neural folds at the cranial end of the embryo. When the neural fold fuse to form the forebrain, the optic grooves will form '''optic vesicles'''. The optic vesicles are continuous cavities from the cavity of the forebrain and project from the wall of the forebrain and into the mesenchyme. The optic vesicle extends from the diencephalon and will come in contact with the surface ectoderm of the head. This induces the formation of a lens placode.

The surface ectoderm near the optic vesicles will thicken and form the '''lens placodes'''. The lens placodes will sink into the surface ectoderm and form '''lens pits'''. The edges of the lens pits will travel towards each other and fuse to form round '''lens vesicles''', which will later lose connection with the surface ectoderm. The optic vesicles do also keep developing - they will form double-walled '''optic cups''' which are connected to the brain by the '''optic stalk'''. The two layers of the optic cup will differentiate in different directions. The cells of the outer layer will produce melanin pigment and later become the '''pigmented retina'''. The cells of the inner layer of the optic cup will proliferate fast and develop glia, ganglion cells, interneurons and light-sensitive photoreceptor neurons. These cells are in the '''neural retina'''. The ganglion cells of the retina are neurons that send signals to the brain. The axons of the ganglion cells of the neural retina will grow in the wall of the optic stalk. The cavity in the optic nerve will start disappearing, and instead, the axons of the ganglion cells will form the '''optic nerve'''. The optic stalk is now the optic nerve <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>

The optic cups will fold inwards around the lens while the lens vesicles have grown inwards so they have fully lost their connection with the surface ectoderm, which locates them in the cavities of the optic cups. The retinal fissures (linear grooves) will develop and cover the ventral surface of the optic cups and down to the optic stalk. The retinal fissures contain vascular mesenchyme and hyaloid blood vessels will develop here. The hyaloid artery supplies the structures in the eye with blood and the hyaloid vein will return the blood from these structures <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

'''Formation of the optic vesicle'''

It is a specific area of the neural ectoderm that will become the optic vesicle - this happens because of a group of transcription factors - Six3, Pax6, and Rx1. These transcription factors are expressed in the most anterior tip of the neural plate. This area will split into bilateral regions and form the optic vesicles. The Pax6 protein has shown to be especially important for the development of the lens and retina. This protein is important for photoreceptive cells in all phyla. Pax 6 is also present in the murine forebrain, hindbrain, and nasal placodes, but the eyes are most sensitive its absence <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

The sonic hedgehog gene is important for the separation of the single eye field into two fields. If this gene is inhibited, the eye field will not split which will result in cyclopia, a single eye in the center of the face <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

===Retina===

[[File:Bailey463.jpg|400px|thumb|right|'''Figure 6.''' Diagram of developing lens and optic cup]]

The retina is the essential component of the eye with the primary function of photoreception <ref><pubmed>7084144</pubmed></ref>. Formation of the retina begins with the specification of retinal cells in the anterior neuroectoderm. First morphological sign of eye development is the formation of two lateral grooves in the anterior neuroectoderm, which is called the optic sulci. The cells of the optic sulci will evaginate and form the optic vesicle. The distal portion of the optic vesicle will form the retina and the proximal will form the optic stalk <ref><pubmed>18675797 </pubmed></ref>. The retina develops from the walls of the optic cup, these walls develop into the two layers of the retina. The thin, outer layer of the optic cup will become the pigment layer of the retina and the thick, inner layer of the optic cup will differentiate into the neural retina. Forkhead transcription factors are regulating the proliferation and differentiation of the retinal precursor cells. During the embryonic and early fetal periods, the two layers of the retina are separated which makes an intraretinal space. The intraretinal space is derived from the cavity of the optic cup. The two layers of the retina will fuse and the intraretinal space will gradually disappear <ref name="Larsen'sHumanEmbryology">Schoenwolf, G.C., Bleyl, S.B., Brauer, P.R., Francis-West, P.H. & Philippa H. (2015). Larsen's human embryology (5th ed.). New York; Edinburgh: Churchill Livingstone.</ref>.

When the lens is developing the inner layer of the optic cup starts to proliferate and forms a thick neuroepithelium which will later differentiate into the neural retina. The neural retina contains photoreceptors and the cell bodies of neurons and is the light-sensitive region of the retina. The axons of the ganglion cells in the neural retina grow in the wall of the optic stalk and will form the optic nerve <ref name="Larsen'sHumanEmbryology">Schoenwolf, G.C., Bleyl, S.B., Brauer, P.R., Francis-West, P.H. & Philippa H. (2015). Larsen's human embryology (5th ed.). New York; Edinburgh: Churchill Livingstone.</ref>.

===Lens===

Human lens induction occurs at around 28 days and is completed around day 56. The surface ectoderm will thicken near the optic vesicle and create the lens placode and later form the lens vesicle <ref><pubmed>20171212 </pubmed></ref>. Lens cells come from ectoderm and differentiate into either lens fibers or the lens epithelium. The anterior monolayer of epithelial cells of the lens will create the lens epithelium, which makes the sheet of cuboidal epithelium covering the anterior surface of the lens. The posterior lens vesicle cells will produce the linear primary fibre cells aligned parallel to the optic axis. These fibres will create the lens mass and form the embryonic lens nucleus. The lens epithelial cells will keep proliferating and produce new cells which generate a secondary lens fiber cells. This rows of cell will form the outer shells and keep the lens growing throughout life. This makes the eye lens unique - it will have an addition of new cells inside the surrounding capsule all the time <ref><pubmed>25406393</pubmed></ref>.

===Ciliary Body===

The ciliary body is a muscular and secretory tissue and is located directly behind the lens. The ciliary body forms part of the anterior segment of the eye and is an important regulator of eye physiology and the vision. The ciliary body produces the aqueous fluid which fills the eyes and nourishes the lens and cornea - this aqueous fluid function to keep the eye in a pressurized and inflated state, which is important the vision.The ciliary body also synthesizes collagenIX and tenasin-C <ref><pubmed>17275804</pubmed></ref>.

The ciliary body extends from the iris root (anteriorly) to the ora serrata (posteriorly). It consist of ciliary muscles and ciliary processes. Each ciliary process (fold) is covered by a double-layered secretory epithelium; the outer pigmented and the inner unpigmented (closes to the lens). The epithelial layers of the ciliary body comes from the retina of the optic cup. We see two different ciliary body epithelium: the inner non-pigmented ciliary epithelium which is connected with the neural retina and the outer pigmented ciliary epithelium which is connected with the retinal pigmented epithelium. The epithelium of the iris is the further anterior extension. The epithelial layers are associated with a stroma containing the ciliary muscle. The ciliary muscle is complex, but can be divided into three portions; anterior, posterior and internal <ref><pubmed>12127103</pubmed></ref>.

In the chick eye development, we see the mesenchyme grow together on the margin of the optic cup and will form the stroma of the ciliary body and the iris, which is located more anteriorly. It is unknown how if the lens has a role in inducing the secretory ciliary body epithelium and the muscular iris epithelium <ref><pubmed>17275804</pubmed></ref>.

===Iris===

The iris is the circular, pigmented muscular portion of the eye with a central aperture that is the pupil. The main function of this round muscle is to manipulate pupil diameter as an adjustment to various conditions and to control the amount of light entering the eye <ref name=’’21413392’’><pubmed>21413392</pubmed></ref>. This is influenced by dilator pupillae (radial) and sphincter pupillae (constricting) muscles. Iris pigmentation is dependent on the abundance and distribution of certain types of melanin in the posterior epithelium of the iris (eumelanin and pheomelanin) <ref name=’’21413392’’/>.

The Iris develops at the end of the third month of development. The iris is a thin layer and derives from the anterior rim of the optic cup <ref><pubmed>22219630</pubmed></ref>. The iris is formed by the pigment-containing internal and external layers of the optic cup and by a layer of vascularised connective tissue which also contains the pupillary muscles. Internal layers of the optic cup form the non-pigmented iris parts whereas the external layers of the optic cup develop into the pigmented epithelial structures. <ref name=’’18168498’’><pubmed>18168498</pubmed></ref>. Iris stroma develops as a result of neural crest cell migration – within this stroma, the dilator and constrictor muscles develop from the neuroectoderm of the optic cup. In the anterior of the eye, the optic epithelium is non-neural and matures as ciliary body and iris epithelia <ref name=’’18168498’’/>.

===Cornea===

The cornea is the unique, transparent and avascular component located at the most anterior section of the eye. It is composed of five layers stemming from the 3 main layers of epithelium, stroma and endothelium:

* Corneal epithelium (most anteriorly) – consisting of multiple layers of cells which rest on a basement membrane.
* Bowman’s membrane – a clear, acellular homogenous layer. This layer is a modified portion of the stroma and has no regenerative capacity as a response to damage <ref name=''7084144''><pubmed>7084144</pubmed></ref>.
* Corneal stroma – largest portion of the retina consisting of collagenous tissue.
* Descemet’s membrane – a homogenous, elastic true basement layer with a regenerative capacity.
* Corneal endothelium – a single layer of cuboidal cells responsible for the maintenance of the dehydrative nature of corneal tissue. <ref name=''7084144''/>.

Corneal development involves interactions between ectoderm-derived tissues. More specifically, the corneal epithelium arises from interactions between the cranial ectoderm and optic vesicles derived from the neural ectoderm <ref name=''26310148''><pubmed>26310148</ref></pubmed>. The neural tube and the adjacent ectoderm give rise to the neural crest cells which are multipotent with a migratory capacity. These cells contribute to the formation of corneal epithelium and the stromal cells. Innervation of the cornea stroma and epithelium is derived from both the neural crest and the ectodermal placode <ref name=''26310148''/>. The endothelium is comprised of differentiated neural crest cells which contribute to the later formation of Descemet’s membrane <ref><pubmed>6511224</pubmed></ref>.

===Aqueous Chambers===

There are two aqueous chambers of the eye: anterior and poster. These chambers are filled with a plasma-like fluid called aqueous humour and is produced by the ciliary body and trabecular meshwork in 3 main stages: diffusion, ultrafiltration and active secretion <ref><pubmed>6763801</pubmed></ref>. The main function of this fluid is to maintain the intraocular pressure as well as provide structural integrity to the round shape of the eyeball. This structure also has a role in the immune response and provides nutrition to the avascular tissue (e.g., the cornea and lens). <ref><pubmed>21293732</pubmed></ref>.

The anterior chamber is defined as the developed space posterior to the cornea (between the cornea and the iris) and develops at the stage of differentiation of the mesodermal portion of the iris <ref name=’’18168498’’/>. The space defining the posterior chamber develops as the mesenchyme between the lens and the peripheral iris.

===Choroid and Sclera===

The choroid and sclera are both surround the eye and are located adjacent to each other (the choroid lines the inner portion of the sclera). The sclera is the outer, fibrous white layer of the eye which functions as a supportive wall of the eye ball and is continuous with the cornea <ref name=''7084144''/> . The heavy vasculature of the choroid provides a major supply of oxygen and nourishment to the retina <ref><pubmed>20044062</pubmed></ref>.
They are derived from interactions between the neural crest and mesoderm-derived mesenchyme. The sclera forms as a result of condensation of the mesenchyme outside the optic cup <ref><pubmed>1628748</pubmed></ref>.
The choroid arises from the mesenchyme surrounding the optic vesicle and the cranial neural crest cells. The first vasculature structures appear in the choroid during week 15 in the form of arterioles and venules; veins and arteries become distinguishable by week 22 <ref name=’’2199235’’><pubmed>2199235</pubmed></ref>.

===Extraocular muscles===

The extraocular muscles are responsible for eye movement within the eye orbit – a critical aspect of sight and communication. 6 main muscles contribute to eye movement. These include: superior rectus, inferior rectus, lateral rectus, medial rectus, superior oblique and inferior oblique.

The development of these muscles is dependent on interactions between the eye, its muscles and the neural crest. <ref name=''21482859''><pubmed>21482859</pubmed></ref>.
Somites supplied by cranial nerve III forms 5 of the 6 extraocular muscles which form an interlocking tendinous ring made of fibrous connective tissue. The 5 muscles include the lateral, medial, superior and inferior rectus, and the superior oblique muscle. This common tendinous ring is known as the annulus of Zinn and surrounds the entry of the optic nerve. The remaining sixth muscle is the inferior oblique muscle and is separate from the aforementioned tendinous ring due to its distinct point of origin. <ref name=''21482859''/>.

===Eyelids===

The eyelids are upper and lower folds of skin functioning as a barrier protecting the anterior surface of the eye from direct local injury. Eyelids also regulate light exposure, distribute precorneal tear film over the corneal surface when blinking and are involved in functions involving tear flow <ref><pubmed>1993591</pubmed></ref>.
No sign of eyelid fold development is evident at week 5 however at this stage the lens pit begins to invaginate from the surface ectoderm <ref name=’’27124372’’><pubmed>27124372</pubmed></ref>. Week 6 initiates the timeline of eyelid development as small depressions emerge in the surface ectoderm both above and below the developing eye – these rapidly deepen to form the folds of the eyelids <ref name=‘’7364662’’><pubmed>7364662</pubmed></ref>. The lower eyelid fold develops first and, by the end of week 6, the lower fold is more distinct than the upper eyelid fold <ref><pubmed>21416630</pubmed></ref>. Week 7 marks the point at which both the upper and lower folds are distinctly developed and during this stage, the upper lid assumes its more dominant role <ref name=’’27124372’’/>. The eyelid is not fully closed - there is a gap between the folds and the cornea is slightly visible – they eventually undergo fusion in week 8 <ref name=’’27124372’’/>.

===Lacrimal Glands===

The lacrimal glands are exocrine glands located in the upper lateral region of each eye orbit which secrete the aqueous potion of the tear film. This film is continuously secreted and functions to clean and protect the external surface of the eye, keeping the environment constantly moist and preventing possible injury from dust and other particles <ref><pubmed>17001201</ref>.
Lacrimal gland morphogenesis is identified in three stages.

* The first is the presumptive glandular stage. This stage involves the thickening of the conjunctival superior fornix epithelium and the condensing of the surrounding mesenchyme <ref name=’’14635806’’><pubmed>14635806</pubmed></ref>.

* The second is the bud stage. This stage is considered the initial sign of glandular formation due to the development of nodular structures and lumina within epithelia buds <ref name=’’14635806’’/>.

* The third is the glandular maturity stage (week 9-16). In this stage, the lacrimal gland begins to morphologically mirror the adult gland <ref name=’’14635806’’/>.

==Signalling pathways and transcription factors involved throughout eye development==

===Eye field development===

Many signalling pathways and transcription factors are involved in the development of the eye field (which forms in addition to the telencephalon and diencephalon as part of division of the anterior neural plate). Eye progenitor cells are guided into the eye field region by fibroblast growth factor, bone morphogenetic protein and Wnt-signalling pathways <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>. Additionally, interactions between canonical and non-canonical Wnt-signalling have been shown to maintain the eye field border <ref name=’’16413771’><pubmed>16413771</pubmed></ref>.

The cells of the eye field express eye field transcription factors, some of which include Rx1/Rax, Pax6, Lhx2, Six3 and Otx2. Six3, Pax6, Otx2 and Rx1 specify retinal lineage and regulate progenitor cell movement to guide them to their correct locations <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>. Six3 also partly mediates Wnt-signalling repression, allowing for the development of the optic vesicles from the eye field <ref name=’’23684892 ’’><pubmed>23684892 </pubmed></ref>. Lhx2 maintains optic lineage in eye progenitor cells and suppresses the potential for differentiation towards different fates <ref name=’’23595746’’><pubmed>23595746</pubmed></ref>.

===Eye field division and progression to optic cup===

TGF-β, FGF and Shh family factors secreted by the axial mesoderm underlying the eye field initiate its splitting into two bilateral, symmetric eye primordia <ref name=’’23684892 ’’><pubmed>23684892 </pubmed></ref>. These factors also regulate the expression of transcription factors Pax2, Pax6, Vax1 and Vax2, thereby establishing the boundaries and patterning the proxiodistal and ventronasal axes of the optic vesicles <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>.

Despite the close relationship between cellular proliferation and morphogenesis, optic vesicle evagination does not appear to be mainly driven by proliferation <ref name=’’23684892 ’’><pubmed>23684892 </pubmed></ref>. Alternatively, it has been shown that retinoic acid has critical importance in optic vesicle evagination to form the optic cup <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>. Rx3 activity has also been observed to have involvement in optic vesicle evagination <ref name=’’23684892 ’’><pubmed>23684892 </pubmed></ref>.

===From optic cup to developed eye===

Lens placode maturation and lens development is dependent on Pax6 expression and regulation. During placode formation bone morphogenetic protein and fibroblast growth factor signalling regulate Pax6. Within the presumptive lens ectoderm, Pax6 is regulated by Six3 and Meis. However, within the presumptive epithelium Pax6 is a regulating factor, regulating the expression of Sox2 and eventually Six3 once the lens placode is formed <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>.

Meanwhile, in the primordial retina retinal progenitor cells become retinal ganglion cells through the expression of the basic helix-loop-helix transcription factor ath5 (which is regulated by Hh and Fgf signalling. The amacrine, horizontal and bipolar cells of the retina are generated by a variety of transcription factors, some of which include Pax6, Six3 and Foxn4 <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>. Crx and Otx2 positive cells progress towards photoreceptor fates and are further developed into rods and cones based on specific transcription factor expression (TRβ2 and RxRγ expression is required for cones, where as Nrl, Nr2e3 and Ascl1 expression is required for rods) <ref name=’’20648062’’><pubmed>20648062</pubmed></ref>. The transcription factors required for the development of the retinal pigment epithelium include Mitf, Otx1/Otx2 and Pax6. TGF-β, FGF, BMP and Hh signalling from the surrounding mesenchyme have also been shown to help induce retinal pigment epithelium fate in progenitor cells <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>.

Within the choroid, the expression and regulation of many different factors and signalling pathways is required for the development of proper arterial-venous connections, allowing for the functional circulation of nutrients and oxygen throughout the eye. VEGF, bFGF, PDGF and PEDF (from the retinal pigment epithelium) drive the development and maturation of choroidal blood vessels. Vascular patterning is regulated by the interactions between VEGF and Delta-like 4 factors. Additionally, Notch signalling has been shown to have importance in the formation of capillary beds <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>.

===Eye formation in the absence of the retina===

The gene Rx is a key component in the formation of retinal structures. Studies have shown that mice lacking Rx function do not form optic sulci or optic vesicles and do not have retina-specific gene expression. There has been made studies in human, medaka, zebrafish and Xenopus which suggest that Rx genes are required for the formation of the vertebrate retina. It is also shown that in Rx-deficient mouse embryos the mature lens does not develop. This indicates that retinal cells are necessary for lens formation, and if the mouse is lacking Rx gene, then it will not display any retina-specific gene expression <ref name="PMC3104407"/>.

It is thought that signaling from the optic vesicle is important to activate the lens-specific gene and the formation of the lens placode. If there are no retinal cells generated, then the morphogenesis of the optic cup does not take place and the lens will not form. The study also showed that elimination of β-catenin expression in the head surface ectoderm in Rx-deficient embryos would develop a lens-like structure even though there were no optic vesicle/cup. Elimination of β-catenin lead to upregulation of Pax6, which is a gene that has a key role in lens formation. This indicates that the optic vesicle/cup might not be required for lens formation. The lens developed smaller than in wild type embryos, which means that the optic cup/vesicle might have an effect on a determination of the size of the lens. It could be that the developing optic vesicle/cup shields the developing lens placode from signals for other tissues that could disturb the lens formation <ref name="PMC3104407"/>.

It is not fully understood if the formation of the auxiliary eye structures is dependent on the development of the eyeball and its components, the retina and the lens. A study made my Eric C. Swindell and al. showed that auxiliary eye structures form even in the absence of retinal morphogenesis and retina-specific gene expression. This indicates that there are two separate developmental processes involved in the formation of the eye and its associated structures. In the absence of the retina and the lens, we still see specific gene expression in the surface ectoderm initiating the formation of auxiliary eye structures like eyelids and lacrimal glands <ref name="PMC3104407"/>.

==Current research==

===Iris epithelium cells as a potential source for regenerative medicine for retinal pigment epithelium degeneration===

The retinal pigment epithelium (RPE) is a monolayer of neural-crest-derived cells and is located between the photoreceptors and the choroid. There are many disorders that involve dysfunctional RPE and leads to retinal degenerative diseases. There is no treatment for these diseases, therefore, one of the most promising future therapy for RPE related disorders is to replace the cells of the dysfunctional RPE <ref name="PMC5565104><pubmed>PMC5565104</pubmed></ref>..

Studies have focused on the development and use of induced pluripotent stem cells (iPSC) for cell replacement therapy. It is possible to differentiate iPSC in vitro towards RPE cells and use them for experimental transplantation studies in animal models. But an alternative strategy for a retinal replacement is based on transdifferentiation (direct conversion) and involves transforming an adult somatic cell into another adult somatic cell. Use of overexpression of cell-lineage specific genes can convert one cell into another cell type and skip the pluripotent state. Iris epithelium (IE) cells might be able to be transdifferentiated into the RPE since both RPE and IE are neuro-epithelia and has a common embryological origin - they both derive from neuroectoderm of the developing optic cup <ref name="PMC5565104"/>.

A study made by Anna Bennis et al. <ref name="PMC5565104"/>. has shown that the canonical pathways for the most highly expressed genes of the IE and the RPE were very similar. Wnt signaling pathways has shown to be active in the IE but not in the RPE. The Wnt signaling pathway consists of a group of signal transduction pathways that has an influence on cell fate determination and cell proliferation during embryonic development. Activation of Wnt SP makes it possible to reprogram somatic cells (also retinal neurons) into iPSC and is important for the differentiation of pluripotent stem cells to RPE cells. The high expression of Wnt SP genes in the iE suggests that the IE has a multipotent character during life and therefore could be transformed into RPE cells used for RPE replacement <ref name="PMC5565104"/>.

==Animal Models==

==Congenital Abnormalities==
Although quite rare, abnormalities can occur during the embryonic development that causes serious effects to the features of the eyes, its function as well as the further normal development after birth. These abnormalities can occur unilaterally or bilaterally and it is also common for most reported cases to have more than one type of eye abnormalities at a time. Thus, the estimated prevalence statistics listed in the table can overlap.

{| class="wikitable"
! style="background:#f4a941" | Congenital Anomalies
! style="background:#f4a941" | Description
! style="background:#f4a941" | Epidemiology
|-
| Anopthalmia || The absence of the eyes.
| rowspan="2" | Prevalence: Anophthalmia-Microphthalmia Syndrome was estimated to be 5.3 per 100 000 cases <ref name="Anophthalmia">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: [[http://www.orpha.net/consor/cgi-bin/index.php]] </ref>
Cause: SOX2 gene mutation <ref name="SOX2 Gene"> Mauri, L., Franzoni, A., Scarcello, M.,
Sala, S., Garavelli, L. Modugno, A., ... Penco, S. (2015). SOX2, OTX2 and PAX6 analysis in subjects with anophthalmia and microphthalmia. ''European Journal of Medical Genetics, 58'', 66-70. doi: 10.1016/j.ejmg.2014.12.005 </ref>
|-
| Microphtalmia || Abnormal reduction in size of the eyeballs.
|-
| Keratoglobus || Structural abnormalities in the formation of the cornea - unknown cause - fixable through surgery<ref name="PMID23807384"><pubmed>23807384</pubmed></ref>
| Prevalence: understood to be a rare condition<ref name="PMID23807384"><pubmed>23807384</pubmed></ref>
|-
| Ptosis ('Lazy Eye')|| Structural abnormalities in the eyelid, can be congenital - specifically the failure of innervation of the oculomotor nerve for levator palpebrae superioris <ref name="PMID8759493"><pubmed>8759493</pubmed></ref> - fixable through surgery<ref name="PMID23807384"><pubmed>23807384</pubmed></ref>
| Prevalence: a relatively well known abnormality
|-
| Coloboma || A condition where parts of the eye is missing and failed to develop normally.
| Prevalence: Occular coloboma was estimated to be 8.0 per 100 000 cases <ref name="Anophthalmia">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: [[http://www.orpha.net/consor/cgi-bin/index.php]] </ref>
|-
| Aniridia || Complete or partial absence of the iris.
| Prevalence: Estimated to be 1.5 per 100 000 cases <ref name="Anophthalmia">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: [[http://www.orpha.net/consor/cgi-bin/index.php]] </ref>
|-
| Optic Nerve Hypoplasia || A condition where the optic nerves are underdeveloped.
| Prevalence: Reported to be the most common abnormality <ref name="The Optic Nerve Hypoplasia">Ryabets-Lienhard, A., Stewart, C., Borchert, M., & Geffner, M. E. (2016). The Optic Nerve Hypoplasia Spectrum - Review of the Literature and Clinical Guidelines. ''Advances in Pediatrics, 63'', 127-146. doi: 10.1016/j.yapd.2016.04.009 </ref>
*10.9 per 100 000 in United Kingdom
*17.3 per 100 000 cases in Sweden.
*6.3% of cases was reported in New Zealand
|-
|}

<gallery>

Anophthalmia.jpeg|'''Figure 7.''' Anopthalmia
Microphthalmia-500px.jpg| '''Figure 8.''' Microphthalmia
Opac_figure_7.jpg| '''Figure 9.''' Iris Coloboma
Opac figure 10.jpg| '''Figure 10.''' Partial Aniridia
</gallery>

==Future questions==
===Will it be possible to have eye transplants in the future?===
Lots of research has been done in making a whole-eye transplantation successful in order to finally cure blindness. Blindness is a worldwide problem and is currently untreatable due to the fact that retinal ganglion cells and the optic nerves do not regenerate. This can result from diseases including macular degeneration and end of stage glaucoma. The first successful eye transplantation was led by Stone and Cole in 1943<ref name="Return of Vision"> Stone, L. S. & Cole, C. H. (1943). Grafted Eyes of Young and Old Adult Salamanders (Amblystoma Punctatum) Showing Return of Vision. ''Yale Journal of Biology and Medicine, 15''(5), 735-754.2. PMCID: PMC2601300</ref> investigating 104 samples of the salamander species, ''Amblystoma Punctatum'', and one of its eyes were either implanted back into the same animal or it was completely transplanted to a new host. It was reported that circulation in the iris was re-established, retina was able to regenerate, a new optic nerve was connected to the brain through the optic chiasma and ocular movements were regained. Vision was reestablished by the second month. In a more recent study, in 2015, Li et al.<ref name="Structural Integrity"> Li, Y., Komatsu, C., Wang, B., Miller, M., Wang, H., van der Merwe, Y., Ho, L., Kostereva, N., Zhang, W., Xiao, B., Davidson, E., Solari, M., Steketee, M. B., Guo, S., Kagemann, L., Wollstein, G., Schuman, J., Chan, K., Gorantla, V. S., Washington, K. M. (2015). Abstract 112: Evaluation of Viability, Structural Integrity and Functional Outcome after Whole Eye Transplantation. ''Plastic & Reconstructive Surgery, 135''(5), 82. "PMC2601300"</ref> investigated the feasibility of eye transplantation by observing the surviving 15 rat models out of the original 22. They were able to confirm the integrity and functional return of vision after whole-eye surgeries with the aid of advance techniques that are available today. The Ear and Eye Foundation of Pittsburgh<ref>'''Ear and Eye Foundation of Pittsburgh''': https://eyeandear.org/our-research/ophthalmology/the-whole-eye-transplant-project</ref> is an organization that is currently running a project with lead researchers to discover a way for the optic nerves to regenerate and to cure blindness by 2020.

===Will the bionic eye pass clinical trials in the next few years?===
The bionic eye is an external visual device that has been in the making for the last several years. It hopes to bring back full vision through the aid of a pair of glasses with a camera attached to it, which then transmits high-frequency radio signals to the microchip implanted in the users' eye. These signals are converted into electrical impulses by the electrodes implanted in the chip, which then stimulates the retinal cells and passes through the optic nerve. Electrical impulses travels to the vision processing centres in the brain and these are then interpreted as an image. At the moment, users must learn to understand light flashes and visual patterns and convert them into images they can interpret. Current prototypes require the users to have a previously working eyes, which means their optic nerves must still be relatively healthy and their visual cortex must be developed. Patients who have suffered from retinitis pigmentosa and age-related macular degeneration would benefit this technology. Bionic Vision Australia<ref>'''Bionic Vision Australia''': http://bionicvision.org.au/about/research_plan</ref> is one of the leading organisations that are aiming to treat blindness and are set to perform clinical trials on two of the devices of the bionic eye implants soon. Their objectives are to develop strategies that can improve the affected visual pathway to the brain by stimulating the remaining working retinal cells and also develop safe surgical procedures.

==Glossary==

{| class="pretty table"
|-bgcolor = "DDCEF2"
|'''Term'''
|'''Definition'''
|-bgcolor="FAF5FF"
|'''Age-related macular degeneration'''||An eye disease with its onset usually after age 60 that can progressively destroy the macula, the central portion of the retina, impairing central vision.
|-
|'''Aqueous humour'''||A transparent fluid similar to plasma with low protein concentrations secreted by the ciliary epithelium.
|-
|'''Choroid'''||The pigmented vascular layer of the eye located between the retina and sclera.
|-
|'''Choroid fissure'''||A ventral groove formed by the invagination of the optic cup located at the bottom of the optic vesicle through which blood vessels enter the eye.
|-
|'''Ciliary body'''||The connection between the iris and choroid consisting of the ciliary muscle, ciliary processes and the ciliary ring. Alters the shape of the lens and ciliary epithelium in order to focus on an image.
|-
|'''Cornea'''||The transparent anterior part of the external coat of the eye covering the iris and pupil and continuous with the sclera.
|-
|'''Ectoderm||The outermost primary germ cell layer in the early embryo.
|-
|'''Endoderm||The innermost primary germ cell layer in the early embryo.
|-
|'''Ectodermal placode'''||A neurogenic placode consisting of an area of thickened epithelium in the embryonic head ectoderm layer that gives rise to neurons and other structures of the sensory system.
|-
|'''Extraocular muscles'''||Muscles controlling eye movement.
|-
|'''Fovea'''||A small depression in the retina where visual acuity is the highest.
|-
|'''Hyaloid vasculature'''||The temporary circulatory system in fetal eyes which spontaneously degenerate when the retinal blood vessels begin to develop.
|-
|'''Intraocular pressure'''||Fluid pressure inside the eye created through continued renewal of fluids.
|-
|'''Iris'''||The coloured muscular ring surrounding the pupil which manipulates the diameter and size of the pupil and controls the amount of light entering the eye.
|-
|'''Lens'''||The transparent biconvex structure posterior to the iris with the main function of focusing light onto the retina in order to form clear images of objects at various distances.
|-
|'''Lens pit'''||A pit-like depression in the fetal head where the lens develops.
|-
|'''Lens placode'''||The placode developing in the ectoderm overlying the optic vesicle, eventually becoming the lens of the eye.
|-
|'''Lens vesicle'''||The ectodermal invagination in the embryo formed opposite the optic cup and gives rise to the lens.
|-
|'''Lumina'''||the central cavity of a tubular structure.
|-
|'''Macula'''||An oval-shaped pigmented area where there is the largest density of cone cells and is involved in producing the sharpness of central vision.
|-
|'''Mesenchyme'''||Loosely organised embryonic connective tissue originating from the mesoderm.
|-
|'''Neural crest'''||A temporary group of embryonic ectodermal cells.
|-
|'''Neural retina'''||Refers to three layers of neural cells within the retina (photoreceptor cells, bipolar cells and ganglion cells).
|-
|'''Neural tube'''||A hollow tubular structure as a result of neural plate folding which later develops into the brain and spinal cord.
|-
|'''Neuroepithelium'''||Epithelium consisting of specialised cells which detect sensory triggers for reception of external stimuli.
|-
|'''Optic cup'''||A structure of the diencephalon formed after optic vesicle folding. This structure gives rise to the retina.
|-
|'''Optic groove'''||Two small grooves on each side of the developing forebrain in the neural folds. Also chiasmatic groove.
|-
|'''Optic nerve'''||Cranial nerve II which transmits impulses to the brain from visual information detected by the photoreceptive retina.
|-
|'''Optic stalk'''||Pair of slender embryonic structures that give rise to the optic nerve.
|-
|'''Optic vesicle'''||An evagination of each lateral all of the embryonic vertebrate forebrain from which the nervous structures of the eye develop.
|-
|'''Pupil'''||The central opening in the iris, allowing and regulating the entry of light into the eye.
|-
|'''Retina'''||The sensory membrane that forms the inner lining of the eye containing rods and cones with the main function of photoreception. Nerve impulses in response to visual information are transmitted to the brain via the optic nerve.
|-
|'''Retinitis Pigmentosa'''||A chronic hereditary eye disease characterized by breakdown and loss of cells in the retina leading to progressive visual loss.
|-
|'''Sclera'''||The dense, white, fibrous membrane that, along with the cornea, forms the external protective covering of the eye
|-
|'''Tear film'''||A layer of tears which spreads over the eye, ultimately maintaining the health of the ocular surface by making the external surface smooth and clear.

|}

{{Glossary}}

==References==

<references/>

==External links==

<pubmed>26956898</pubmed>

2017 Group Project 4

2017-10-25T23:53:28Z

Z3416557:

{{ANAT2341Project2017header}}

=Eye Development=

==Introduction==

==Anatomy of the Adult Eye==

The eye is a complex sensory structure which allows a variety of species to intake and process visual information from the world around us.

To discuss the key anatomical components of the eye, we will break down the eye in parts<ref>Chen, J., 2011. Handbook of Visual Display Technology. Springer Berlin Heidelberg. Chapter 2.1</ref>:

'''Supporting Structures (Orbit, Extraoccular Muscles, Lacrimal Gland, Eyelid)'''
[[File:22292144 10208413540209536 722417340 o.jpg|250px|thumb|right| '''Figure 1.''' Layers of the Eyeball]]
The orbit of the eye consists of a framework of bones and connective tissue which provide structural support and protection to the sensitive human eye. 7 bones contribute to the orbit of the eye: frontal, lacrimal, sphenoid, zygomtatic, ethmoid, maxilary, palatine. Several openings exist in the orbital structure, 2 key fissures are the superior orbital fissure and inferior orbital fissure and the posterior optic canal. These openings allow crainial nerves passageway.

A set of 6 extraoccular muscles allow for a strong voluntary control of the movement of the eye. These muscles include superior recuts, inferior rectus, lateral rectus, medial rectus, inferior oblique, superior oblique muscles. These muscles are some of the smallest in the human body and are designed to produce fast, controlled motion to focus on an object of interest.

The eyelid is the anterior covering of the eye, consisting of a thin fold of skin. It is controlled by the levitator palpabrae superioris muscle. Superio-laterally to the eyelid is the lacrimal gland, which serves to create a film of tear, an important component to keeping the anterior surface of the eye moist. The eyelid assists in this process by opening and closing, or blinking, which spreads the tear film across the surface of the eye. Tear film and debris caught in the tear film are excreted through the lacrimal duct which is located on the infero-medial surface of the eyelid.
[[File:22251179_10208414266827701_870733039_o.jpg|250px|thumb|right| '''Figure 2.''' Anterior Part of the Eye]]

'''Layers of the Eyeball (Sclera, Choroid, Retina)'''

The superficial layers of the eyeball is the sclera, a thick fibrous layer which becomes thicker as it extends posteriorly. The sclera is the visible as the white part of our eye. It's function is to provide structural stability to the eye and serves as attachment for some extraoccular insertions. Deep to the sclera is the choroid, a vascular network which provides nourishment to the layers of the eyeball and plays a large role in the growth of the eye. Deep to the choroid is the retina, a network of nerve fibers which transmit visual information. The retina contains 2 types of photoreceptors which convert visible light into nerve impulses. Rods work best in low light environments while cones work best in high light enthronements and detect colour and sharp detail.<ref>Curcio CA, Hendrickson AE. Organization and development of the primate photoreceptor mosaic. Prog Ret Ret. 1991;10:89–120.</ref>: The retina does not extend to the anterior part of the eyeball, unlike the sclera and choroid layers.

'''Anterior structure (Lens, Cornea, Pupil, Iris, Ciliary Body, Conjunctiva Anterior Chamber)'''

The most anterior component of the eyeball is the cornea, which is a multilayered avascular transparent structure who's major function to the refract light to assist image formation (contributes about 75% of total refraction). Continuous with cornea superiorly and inferiorly is the conjunctiva. Deep to the cornera is the iris, or the coloured ring visible in the eye. The iris consists of 2 muscles which act to enhance and diminish the size of the pupil, a hole in the middle of the iris allowing light to enter the eye. Deep to the pupil and iris is the lens, which is a transparent structure which contributes the other 25% of the eye's refractive power. The lens changes shape through accomodation controlled by the ciliary body muscles. The ciliary body is the anterior extension of the choroid. The function of the lens is to focus images by changing refractive power based on the position and depth of focal objects. In between the anterior surface of the lens and posterior surface of the cornea is the anterior chamber. This chamber is filled with aqueous humor supplied by the ciliary body, who's function is to provide nutrients to ocular structures and maintain intraocular pressure.
[[File:22251314_10208414283908128_862494115_o.jpg|250px|thumb|right| '''Figure 3.''' Posterior Part of the Eye]]

'''Posterior structure (Optic Nerve, Optic Disc, Macula, Fovea, Posterior Chamber)'''

In the posterior section of the retina is the macula, a central spot in which a high concentration of cone photoreceptors are found. The direct centre of the macula is called the fovea which contains solely cone photoreceptors. The fovea is only part of the eye which can conduct 'perfect' 20/20 vision. It has a high workload and hence a strong vascular supporting structure<ref><pubmed>6462623</pubmed></ref>:. The most posterior part of the eye is the optic nerve (along with the central retinal artery and central retinal vein), which is responsible for transporting nerve impulses to the cerebral cortex for processing. The opening of the optic nerve is called the optic disc, which contains no photoreceptors and is a blind spot of the eye. Between the posterior surface of the lens, the retina and the optic disc is the posterior chamber. The posterior chamber contains a vitreous humour, a jelly like substance with a high viscosity.

==Embryonic Contributions==

Eye development is a complex process. It involves the formation of the retina and the lens, which we together call the eyeball. It also involves the formation of auxiliary eye structures which are the eyelid, lacrimal gland, and cornea. The retina is formed from the neuroectoderm, the lens from the surface ectoderm and the auxiliary tissues are formed from the head surface ectoderm, neural crest cells and the head mesoderm <ref name="PMC3104407><pubmed>PMC3104407</pubmed></ref>.

[[File:Stage14 sem2cl.jpg|300px|thumb|right| '''Figure 4.''' Stage 14]]

{| class="wikitable"
! style="background:#f4a941" | Embryonic contributions
! style="background:#f4a941" | Eye component
|-
| Neuroectoderm of the forebrain || Retina, Posterior layers of the iris, The optic nerve
|-
| Surface ectoderm of the head || The lens of the eye, The corneal epithelium
|-
| Mesoderm between the neuroectoderm and the surface ectoderm || The fibrous and vascular coats of the eye
|-
| Neural crest cells || Choroid, Sclera, Corneal endothelium
|}

==Timeline of embryonic development==

{| class="wikitable"
! style="background:#f4a941" | WEEK
! style="background:#f4a941" | DEVELOPMENT
|-
| 3-4 || Eye fields, Optic vesicles
|-
| 5-6 || Optic Cup, Lens Vesicle, Choroid Fissure, Hyaloid Artery
|-
| 7-8 || Cornea, Anterior Chamber, Pupillary Membrane, Lens, Retina
|-
| 8-10 || Eyelids
|-
| 9-15 || Iris, Ciliary Body
|}

==Carnegie Stages==

Carnegie Stages is a system of 23 stages used to describe developmental events of the vertebrate embryo. At stage 10 we see early signs related to eye development. The table below is an made of knowledge from Anthony A. Person's article <ref><pubmed>7364662</pubmed></ref>.

{| class="pretty table"
|-bgcolor = "DDCEF2"
|'''Stage'''
|'''Events'''
|-bgcolor="FAF5FF"
|'''Stage 10 (22 days)'''
|The optic primordium has developed. Two small grooves develop on each side of the developing forebrain in the neural folds - this is the optic grooves. The optic placode has begun to develop, which is seen by a small thickening of the surface ectoderm lateral to the hindbrain.
|-
|'''Stage 11 (24 days)'''
|Optic vesicle begins to form from the optic groove.

[[File:Stage11 histology-optic pit.jpg|300px|'''Figure 1.''' Stage 11]]
|-bgcolor="FAF5FF"
|'''Stage 12 (26 days)'''
|The optic vesicles have extended from the forbrain to the surface ectoderm. The optic vesicle now lies close to the surface ectoderm.
|-
|'''Stage 13 (28 days)'''
| The optic vesicle interacts with the surface ectoderm and will induce this ectoderm to form the lens placode, which is the precursor of the lens. Optic evagination differentiation makes it possible to identiy optic parts of retina, future pigmented layer of retina and optic stalk.

[[File:Stage_13_image_060.jpg|300px|'''Figure 2.''' Stage 13]]
|-bgcolor="FAF5FF"
|'''Stage 14 (32 days)'''
| The lens placode is indented by the lens pit and is be cup-shaped.
|-
| '''Stage 15 (33 days)'''
| The lens pit will close and form a circle that separates from the surface ectoderm and becomes the lens vesicle. The lens vesicle and optic cub lie close to the surface ectoderm, which creates a slight elevation in the region of the eye.
|-bgcolor="FAF5FF"
| '''Stage 16 (37 days )'''
| The lens body has grown and now has a D-shaped lens cavity. First indication of the development of the eyelids visible as eyelid grooves above and below the eye.
|-
| '''Stage 17 - 19'''
| Retinal pigment is visible and the retinal fissure is almost closed. The eyes are still laterally placed but starts to take a more anterior position. The lower eyelid fold develops first and then the eyelid fold above the eye.
|-bgcolor="FAF5FF"
| '''Stage 18 (44 days)'''
| Mesenchyme invades the region between the lens epithelium and the surface ectoderm. The eyes have shifted to a more anterior position. The groove above and below the eyes are deeper but have not joined yet.
|-
| '''Stage 19 - 22'''
| The eyelid folds develop into the eyelids and the upper and the lower eyelids now meet at the outer canthus, which is the corner of the eye.

[[File:Stage 22 image 208.jpg|300px|'''Figure 3.''' Stage 22]]
|-bgcolor="FAF5FF"
| '''Stage 20 (51 days)'''
| The lens cavity is lost. The upper and lower lids meet laterally and medially. The eyelids now partly cover the eye. Lens suture begins to form.
|-
| '''Stage 23 (57 days)'''
| End of embryonic period. The face begins to look human. Eyelids closure is complete.
|-
|-bgcolor="FAF5FF"
|-
|}

==Development of the eye components==

===Introduction===

<html5media width=“480" height="360">https://www.youtube.com/embed/ghHDFWlfpoQ</html5media>

[[File:DevelopmentEye-PMC43029243.jpg|400px|thumb|right|'''Figure 5.''' Stages of lens formation in mouse embryos]]

The eye starts to develop at 22 days. The optic grooves (sulci) appears in the neural folds at the cranial end of the embryo. When the neural fold fuse to form the forebrain, the optic grooves will form '''optic vesicles'''. The optic vesicles are continuous cavities from the cavity of the forebrain and project from the wall of the forebrain and into the mesenchyme. The optic vesicle extends from the diencephalon and will come in contact with the surface ectoderm of the head. This induces the formation of a lens placode.

The surface ectoderm near the optic vesicles will thicken and form the '''lens placodes'''. The lens placodes will sink into the surface ectoderm and form '''lens pits'''. The edges of the lens pits will travel towards each other and fuse to form round '''lens vesicles''', which will later lose connection with the surface ectoderm. The optic vesicles do also keep developing - they will form double-walled '''optic cups''' which are connected to the brain by the '''optic stalk'''. The two layers of the optic cup will differentiate in different directions. The cells of the outer layer will produce melanin pigment and later become the '''pigmented retina'''. The cells of the inner layer of the optic cup will proliferate fast and develop glia, ganglion cells, interneurons and light-sensitive photoreceptor neurons. These cells are in the '''neural retina'''. The ganglion cells of the retina are neurons that send signals to the brain. The axons of the ganglion cells of the neural retina will grow in the wall of the optic stalk. The cavity in the optic nerve will start disappearing, and instead, the axons of the ganglion cells will form the '''optic nerve'''. The optic stalk is now the optic nerve <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>

The optic cups will fold inwards around the lens while the lens vesicles have grown inwards so they have fully lost their connection with the surface ectoderm, which locates them in the cavities of the optic cups. The retinal fissures (linear grooves) will develop and cover the ventral surface of the optic cups and down to the optic stalk. The retinal fissures contain vascular mesenchyme and hyaloid blood vessels will develop here. The hyaloid artery supplies the structures in the eye with blood and the hyaloid vein will return the blood from these structures <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

'''Formation of the optic vesicle'''

It is a specific area of the neural ectoderm that will become the optic vesicle - this happens because of a group of transcription factors - Six3, Pax6, and Rx1. These transcription factors are expressed in the most anterior tip of the neural plate. This area will split into bilateral regions and form the optic vesicles. The Pax6 protein has shown to be especially important for the development of the lens and retina. This protein is important for photoreceptive cells in all phyla. Pax 6 is also present in the murine forebrain, hindbrain, and nasal placodes, but the eyes are most sensitive its absence <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

The sonic hedgehog gene is important for the separation of the single eye field into two fields. If this gene is inhibited, the eye field will not split which will result in cyclopia, a single eye in the center of the face <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

===Retina===

[[File:Bailey463.jpg|400px|thumb|right|'''Figure 6.''' Diagram of developing lens and optic cup]]

The retina is the essential component of the eye with the primary function of photoreception <ref><pubmed>7084144</pubmed></ref>. Formation of the retina begins with the specification of retinal cells in the anterior neuroectoderm. First morphological sign of eye development is the formation of two lateral grooves in the anterior neuroectoderm, which is called the optic sulci. The cells of the optic sulci will evaginate and form the optic vesicle. The distal portion of the optic vesicle will form the retina and the proximal will form the optic stalk <ref><pubmed>18675797 </pubmed></ref>. The retina develops from the walls of the optic cup, these walls develop into the two layers of the retina. The thin, outer layer of the optic cup will become the pigment layer of the retina and the thick, inner layer of the optic cup will differentiate into the neural retina. Forkhead transcription factors are regulating the proliferation and differentiation of the retinal precursor cells. During the embryonic and early fetal periods, the two layers of the retina are separated which makes an intraretinal space. The intraretinal space is derived from the cavity of the optic cup. The two layers of the retina will fuse and the intraretinal space will gradually disappear <ref name="Larsen'sHumanEmbryology">Schoenwolf, G.C., Bleyl, S.B., Brauer, P.R., Francis-West, P.H. & Philippa H. (2015). Larsen's human embryology (5th ed.). New York; Edinburgh: Churchill Livingstone.</ref>.

When the lens is developing the inner layer of the optic cup starts to proliferate and forms a thick neuroepithelium which will later differentiate into the neural retina. The neural retina contains photoreceptors and the cell bodies of neurons and is the light-sensitive region of the retina. The axons of the ganglion cells in the neural retina grow in the wall of the optic stalk and will form the optic nerve <ref name="Larsen'sHumanEmbryology">Schoenwolf, G.C., Bleyl, S.B., Brauer, P.R., Francis-West, P.H. & Philippa H. (2015). Larsen's human embryology (5th ed.). New York; Edinburgh: Churchill Livingstone.</ref>.

===Lens===

Human lens induction occurs at around 28 days and is completed around day 56. The surface ectoderm will thicken near the optic vesicle and create the lens placode and later form the lens vesicle <ref><pubmed>20171212 </pubmed></ref>. Lens cells come from ectoderm and differentiate into either lens fibers or the lens epithelium. The anterior monolayer of epithelial cells of the lens will create the lens epithelium, which makes the sheet of cuboidal epithelium covering the anterior surface of the lens. The posterior lens vesicle cells will produce the linear primary fibre cells aligned parallel to the optic axis. These fibres will create the lens mass and form the embryonic lens nucleus. The lens epithelial cells will keep proliferating and produce new cells which generate a secondary lens fiber cells. This rows of cell will form the outer shells and keep the lens growing throughout life. This makes the eye lens unique - it will have an addition of new cells inside the surrounding capsule all the time <ref><pubmed>25406393</pubmed></ref>.

===Ciliary Body===

The ciliary body is a muscular and secretory tissue and is located directly behind the lens. The ciliary body forms part of the anterior segment of the eye and is an important regulator of eye physiology and the vision. The ciliary body produces the aqueous fluid which fills the eyes and nourishes the lens and cornea - this aqueous fluid function to keep the eye in a pressurized and inflated state, which is important the vision.The ciliary body also synthesizes collagenIX and tenasin-C <ref><pubmed>17275804</pubmed></ref>.

The ciliary body extends from the iris root (anteriorly) to the ora serrata (posteriorly). It consist of ciliary muscles and ciliary processes. Each ciliary process (fold) is covered by a double-layered secretory epithelium; the outer pigmented and the inner unpigmented (closes to the lens). The epithelial layers of the ciliary body comes from the retina of the optic cup. We see two different ciliary body epithelium: the inner non-pigmented ciliary epithelium which is connected with the neural retina and the outer pigmented ciliary epithelium which is connected with the retinal pigmented epithelium. The epithelium of the iris is the further anterior extension. The epithelial layers are associated with a stroma containing the ciliary muscle. The ciliary muscle is complex, but can be divided into three portions; anterior, posterior and internal <ref><pubmed>12127103</pubmed></ref>.

In the chick eye development, we see the mesenchyme grow together on the margin of the optic cup and will form the stroma of the ciliary body and the iris, which is located more anteriorly. It is unknown how if the lens has a role in inducing the secretory ciliary body epithelium and the muscular iris epithelium <ref><pubmed>17275804</pubmed></ref>.

===Iris===

The iris is the circular, pigmented muscular portion of the eye with a central aperture that is the pupil. The main function of this round muscle is to manipulate pupil diameter as an adjustment to various conditions and to control the amount of light entering the eye <ref name=’’21413392’’><pubmed>21413392</pubmed></ref>. This is influenced by dilator pupillae (radial) and sphincter pupillae (constricting) muscles. Iris pigmentation is dependent on the abundance and distribution of certain types of melanin in the posterior epithelium of the iris (eumelanin and pheomelanin) <ref name=’’21413392’’/>.

The Iris develops at the end of the third month of development. The iris is a thin layer and derives from the anterior rim of the optic cup <ref><pubmed>22219630</pubmed></ref>. The iris is formed by the pigment-containing internal and external layers of the optic cup and by a layer of vascularised connective tissue which also contains the pupillary muscles. Internal layers of the optic cup form the non-pigmented iris parts whereas the external layers of the optic cup develop into the pigmented epithelial structures. <ref name=’’18168498’’><pubmed>18168498</pubmed></ref>. Iris stroma develops as a result of neural crest cell migration – within this stroma, the dilator and constrictor muscles develop from the neuroectoderm of the optic cup. In the anterior of the eye, the optic epithelium is non-neural and matures as ciliary body and iris epithelia <ref name=’’18168498’’/>.

===Cornea===

The cornea is the unique, transparent and avascular component located at the most anterior section of the eye. It is composed of five layers stemming from the 3 main layers of epithelium, stroma and endothelium:

* Corneal epithelium (most anteriorly) – consisting of multiple layers of cells which rest on a basement membrane.
* Bowman’s membrane – a clear, acellular homogenous layer. This layer is a modified portion of the stroma and has no regenerative capacity as a response to damage <ref name=''7084144''><pubmed>7084144</pubmed></ref>.
* Corneal stroma – largest portion of the retina consisting of collagenous tissue.
* Descemet’s membrane – a homogenous, elastic true basement layer with a regenerative capacity.
* Corneal endothelium – a single layer of cuboidal cells responsible for the maintenance of the dehydrative nature of corneal tissue. <ref name=''7084144''/>.

Corneal development involves interactions between ectoderm-derived tissues. More specifically, the corneal epithelium arises from interactions between the cranial ectoderm and optic vesicles derived from the neural ectoderm <ref name=''26310148''><pubmed>26310148</ref></pubmed>. The neural tube and the adjacent ectoderm give rise to the neural crest cells which are multipotent with a migratory capacity. These cells contribute to the formation of corneal epithelium and the stromal cells. Innervation of the cornea stroma and epithelium is derived from both the neural crest and the ectodermal placode <ref name=''26310148''/>. The endothelium is comprised of differentiated neural crest cells which contribute to the later formation of Descemet’s membrane <ref><pubmed>6511224</pubmed></ref>.

===Aqueous Chambers===

There are two aqueous chambers of the eye: anterior and poster. These chambers are filled with a plasma-like fluid called aqueous humour and is produced by the ciliary body and trabecular meshwork in 3 main stages: diffusion, ultrafiltration and active secretion <ref><pubmed>6763801</pubmed></ref>. The main function of this fluid is to maintain the intraocular pressure as well as provide structural integrity to the round shape of the eyeball. This structure also has a role in the immune response and provides nutrition to the avascular tissue (e.g., the cornea and lens). <ref><pubmed>21293732</pubmed></ref>.

The anterior chamber is defined as the developed space posterior to the cornea (between the cornea and the iris) and develops at the stage of differentiation of the mesodermal portion of the iris <ref name=’’18168498’’/>. The space defining the posterior chamber develops as the mesenchyme between the lens and the peripheral iris.

===Choroid and Sclera===

The choroid and sclera are both surround the eye and are located adjacent to each other (the choroid lines the inner portion of the sclera). The sclera is the outer, fibrous white layer of the eye which functions as a supportive wall of the eye ball and is continuous with the cornea <ref name=''7084144''/> . The heavy vasculature of the choroid provides a major supply of oxygen and nourishment to the retina <ref><pubmed>20044062</pubmed></ref>.
They are derived from interactions between the neural crest and mesoderm-derived mesenchyme. The sclera forms as a result of condensation of the mesenchyme outside the optic cup <ref><pubmed>1628748</pubmed></ref>.
The choroid arises from the mesenchyme surrounding the optic vesicle and the cranial neural crest cells. The first vasculature structures appear in the choroid during week 15 in the form of arterioles and venules; veins and arteries become distinguishable by week 22 <ref name=’’2199235’’><pubmed>2199235</pubmed></ref>.

===Extraocular muscles===

The extraocular muscles are responsible for eye movement within the eye orbit – a critical aspect of sight and communication. 6 main muscles contribute to eye movement. These include: superior rectus, inferior rectus, lateral rectus, medial rectus, superior oblique and inferior oblique.

The development of these muscles is dependent on interactions between the eye, its muscles and the neural crest. <ref name=''21482859''><pubmed>21482859</pubmed></ref>.
Somites supplied by cranial nerve III forms 5 of the 6 extraocular muscles which form an interlocking tendinous ring made of fibrous connective tissue. The 5 muscles include the lateral, medial, superior and inferior rectus, and the superior oblique muscle. This common tendinous ring is known as the annulus of Zinn and surrounds the entry of the optic nerve. The remaining sixth muscle is the inferior oblique muscle and is separate from the aforementioned tendinous ring due to its distinct point of origin. <ref name=''21482859''/>.

===Eyelids===

The eyelids are upper and lower folds of skin functioning as a barrier protecting the anterior surface of the eye from direct local injury. Eyelids also regulate light exposure, distribute precorneal tear film over the corneal surface when blinking and are involved in functions involving tear flow <ref><pubmed>1993591</pubmed></ref>.
No sign of eyelid fold development is evident at week 5 however at this stage the lens pit begins to invaginate from the surface ectoderm <ref name=’’27124372’’><pubmed>27124372</pubmed></ref>. Week 6 initiates the timeline of eyelid development as small depressions emerge in the surface ectoderm both above and below the developing eye – these rapidly deepen to form the folds of the eyelids <ref name=‘’7364662’’><pubmed>7364662</pubmed></ref>. The lower eyelid fold develops first and, by the end of week 6, the lower fold is more distinct than the upper eyelid fold <ref><pubmed>21416630</pubmed></ref>. Week 7 marks the point at which both the upper and lower folds are distinctly developed and during this stage, the upper lid assumes its more dominant role <ref name=’’27124372’’/>. The eyelid is not fully closed - there is a gap between the folds and the cornea is slightly visible – they eventually undergo fusion in week 8 <ref name=’’27124372’’/>.

===Lacrimal Glands===

The lacrimal glands are exocrine glands located in the upper lateral region of each eye orbit which secrete the aqueous potion of the tear film. This film is continuously secreted and functions to clean and protect the external surface of the eye, keeping the environment constantly moist and preventing possible injury from dust and other particles <ref><pubmed>17001201</ref>.
Lacrimal gland morphogenesis is identified in three stages.

* The first is the presumptive glandular stage. This stage involves the thickening of the conjunctival superior fornix epithelium and the condensing of the surrounding mesenchyme <ref name=’’14635806’’><pubmed>14635806</pubmed></ref>.

* The second is the bud stage. This stage is considered the initial sign of glandular formation due to the development of nodular structures and lumina within epithelia buds <ref name=’’14635806’’/>.

* The third is the glandular maturity stage (week 9-16). In this stage, the lacrimal gland begins to morphologically mirror the adult gland <ref name=’’14635806’’/>.

==Signalling pathways and transcription factors involved throughout eye development==

===Eye field development===

Many signalling pathways and transcription factors are involved in the development of the eye field (which forms in addition to the telencephalon and diencephalon as part of division of the anterior neural plate). Eye progenitor cells are guided into the eye field region by fibroblast growth factor, bone morphogenetic protein and Wnt-signalling pathways <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>. Additionally, interactions between canonical and non-canonical Wnt-signalling have been shown to maintain the eye field border <ref name=’’16413771’><pubmed>16413771</pubmed></ref>.

The cells of the eye field express eye field transcription factors, some of which include Rx1/Rax, Pax6, Lhx2, Six3 and Otx2. Six3, Pax6, Otx2 and Rx1 specify retinal lineage and regulate progenitor cell movement to guide them to their correct locations <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>. Six3 also partly mediates Wnt-signalling repression, allowing for the development of the optic vesicles from the eye field <ref name=’’23684892 ’’><pubmed>23684892 </pubmed></ref>. Lhx2 maintains optic lineage in eye progenitor cells and suppresses the potential for differentiation towards different fates <ref name=’’23595746’’><pubmed>23595746</pubmed></ref>.

===Eye field division and progression to optic cup===

TGF-β, FGF and Shh family factors secreted by the axial mesoderm underlying the eye field initiate its splitting into two bilateral, symmetric eye primordia <ref name=’’23684892 ’’><pubmed>23684892 </pubmed></ref>. These factors also regulate the expression of transcription factors Pax2, Pax6, Vax1 and Vax2, thereby establishing the boundaries and patterning the proxiodistal and ventronasal axes of the optic vesicles <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>.

Despite the close relationship between cellular proliferation and morphogenesis, optic vesicle evagination does not appear to be mainly driven by proliferation <ref name=’’23684892 ’’><pubmed>23684892 </pubmed></ref>. Alternatively, it has been shown that retinoic acid has critical importance in optic vesicle evagination to form the optic cup <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>. Rx3 activity has also been observed to have involvement in optic vesicle evagination <ref name=’’23684892 ’’><pubmed>23684892 </pubmed></ref>.

===From optic cup to developed eye===

Lens placode maturation and lens development is dependent on Pax6 expression and regulation. During placode formation bone morphogenetic protein and fibroblast growth factor signalling regulate Pax6. Within the presumptive lens ectoderm, Pax6 is regulated by Six3 and Meis. However, within the presumptive epithelium Pax6 is a regulating factor, regulating the expression of Sox2 and eventually Six3 once the lens placode is formed <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>.

Meanwhile, in the primordial retina retinal progenitor cells become retinal ganglion cells through the expression of the basic helix-loop-helix transcription factor ath5 (which is regulated by Hh and Fgf signalling. The amacrine, horizontal and bipolar cells of the retina are generated by a variety of transcription factors, some of which include Pax6, Six3 and Foxn4 <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>. Crx and Otx2 positive cells progress towards photoreceptor fates and are further developed into rods and cones based on specific transcription factor expression (TRβ2 and RxRγ expression is required for cones, where as Nrl, Nr2e3 and Ascl1 expression is required for rods) <ref name=’’20648062’’><pubmed>20648062</pubmed></ref>. The transcription factors required for the development of the retinal pigment epithelium include Mitf, Otx1/Otx2 and Pax6. TGF-β, FGF, BMP and Hh signalling from the surrounding mesenchyme have also been shown to help induce retinal pigment epithelium fate in progenitor cells <ref name=’’25476579’’><pubmed>25476579</pubmed></ref>.

===Eye formation in the absence of the retina===

The gene Rx is a key component in the formation of retinal structures. Studies have shown that mice lacking Rx function do not form optic sulci or optic vesicles and do not have retina-specific gene expression. There has been made studies in human, medaka, zebrafish and Xenopus which suggest that Rx genes are required for the formation of the vertebrate retina. It is also shown that in Rx-deficient mouse embryos the mature lens does not develop. This indicates that retinal cells are necessary for lens formation, and if the mouse is lacking Rx gene, then it will not display any retina-specific gene expression <ref name="PMC3104407"/>.

It is thought that signaling from the optic vesicle is important to activate the lens-specific gene and the formation of the lens placode. If there are no retinal cells generated, then the morphogenesis of the optic cup does not take place and the lens will not form. The study also showed that elimination of β-catenin expression in the head surface ectoderm in Rx-deficient embryos would develop a lens-like structure even though there were no optic vesicle/cup. Elimination of β-catenin lead to upregulation of Pax6, which is a gene that has a key role in lens formation. This indicates that the optic vesicle/cup might not be required for lens formation. The lens developed smaller than in wild type embryos, which means that the optic cup/vesicle might have an effect on a determination of the size of the lens. It could be that the developing optic vesicle/cup shields the developing lens placode from signals for other tissues that could disturb the lens formation <ref name="PMC3104407"/>.

It is not fully understood if the formation of the auxiliary eye structures is dependent on the development of the eyeball and its components, the retina and the lens. A study made my Eric C. Swindell and al. showed that auxiliary eye structures form even in the absence of retinal morphogenesis and retina-specific gene expression. This indicates that there are two separate developmental processes involved in the formation of the eye and its associated structures. In the absence of the retina and the lens, we still see specific gene expression in the surface ectoderm initiating the formation of auxiliary eye structures like eyelids and lacrimal glands <ref name="PMC3104407"/>.

==Current research==

===Iris epithelium cells as a potential source for regenerative medicine for retinal pigment epithelium degeneration===

The retinal pigment epithelium (RPE) is a monolayer of neural-crest-derived cells and is located between the photoreceptors and the choroid. There are many disorders that involve dysfunctional RPE and leads to retinal degenerative diseases. There is no treatment for these diseases, therefore, one of the most promising future therapy for RPE related disorders is to replace the cells of the dysfunctional RPE <ref name="PMC5565104><pubmed>PMC5565104</pubmed></ref>..

Studies have focused on the development and use of induced pluripotent stem cells (iPSC) for cell replacement therapy. It is possible to differentiate iPSC in vitro towards RPE cells and use them for experimental transplantation studies in animal models. But an alternative strategy for a retinal replacement is based on transdifferentiation (direct conversion) and involves transforming an adult somatic cell into another adult somatic cell. Use of overexpression of cell-lineage specific genes can convert one cell into another cell type and skip the pluripotent state. Iris epithelium (IE) cells might be able to be transdifferentiated into the RPE since both RPE and IE are neuro-epithelia and has a common embryological origin - they both derive from neuroectoderm of the developing optic cup <ref name="PMC5565104"/>.

A study made by Anna Bennis et al. <ref name="PMC5565104"/>. has shown that the canonical pathways for the most highly expressed genes of the IE and the RPE were very similar. Wnt signaling pathways has shown to be active in the IE but not in the RPE. The Wnt signaling pathway consists of a group of signal transduction pathways that has an influence on cell fate determination and cell proliferation during embryonic development. Activation of Wnt SP makes it possible to reprogram somatic cells (also retinal neurons) into iPSC and is important for the differentiation of pluripotent stem cells to RPE cells. The high expression of Wnt SP genes in the iE suggests that the IE has a multipotent character during life and therefore could be transformed into RPE cells used for RPE replacement <ref name="PMC5565104"/>.

==Animal Models==

==Congenital Abnormalities==
Although quite rare, abnormalities can occur during the embryonic development that causes serious effects to the features of the eyes, its function as well as the further normal development after birth. These abnormalities can occur unilaterally or bilaterally and it is also common for most reported cases to have more than one type of eye abnormalities at a time. Thus, the estimated prevalence statistics listed in the table can overlap.

{| class="wikitable"
! style="background:#f4a941" | Congenital Anomalies
! style="background:#f4a941" | Description
! style="background:#f4a941" | Epidemiology
|-
| Anopthalmia || The absence of the eyes.
| rowspan="2" | Prevalence: Anophthalmia-Microphthalmia Syndrome was estimated to be 5.3 per 100 000 cases <ref name="Anophthalmia">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: [[http://www.orpha.net/consor/cgi-bin/index.php]] </ref>
Cause: SOX2 gene mutation <ref name="SOX2 Gene"> Mauri, L., Franzoni, A., Scarcello, M.,
Sala, S., Garavelli, L. Modugno, A., ... Penco, S. (2015). SOX2, OTX2 and PAX6 analysis in subjects with anophthalmia and microphthalmia. ''European Journal of Medical Genetics, 58'', 66-70. doi: 10.1016/j.ejmg.2014.12.005 </ref>
|-
| Microphtalmia || Abnormal reduction in size of the eyeballs.
|-
| Keratoglobus || Structural abnormalities in the formation of the cornea - unknown cause - fixable through surgery<ref><pubmed>23807384</pubmed></ref>
| Prevalence: understood to be a rare condition<ref><pubmed>23807384</pubmed></ref>
|-
| Coloboma || A condition where parts of the eye is missing and failed to develop normally.
| Prevalence: Occular coloboma was estimated to be 8.0 per 100 000 cases <ref name="Anophthalmia">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: [[http://www.orpha.net/consor/cgi-bin/index.php]] </ref>
|-
| Aniridia || Complete or partial absence of the iris.
| Prevalence: Estimated to be 1.5 per 100 000 cases <ref name="Anophthalmia">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: [[http://www.orpha.net/consor/cgi-bin/index.php]] </ref>
|-
| Optic Nerve Hypoplasia || A condition where the optic nerves are underdeveloped.
| Prevalence: Reported to be the most common abnormality <ref name="The Optic Nerve Hypoplasia">Ryabets-Lienhard, A., Stewart, C., Borchert, M., & Geffner, M. E. (2016). The Optic Nerve Hypoplasia Spectrum - Review of the Literature and Clinical Guidelines. ''Advances in Pediatrics, 63'', 127-146. doi: 10.1016/j.yapd.2016.04.009 </ref>
*10.9 per 100 000 in United Kingdom
*17.3 per 100 000 cases in Sweden.
*6.3% of cases was reported in New Zealand
|-
|}

<gallery>

Anophthalmia.jpeg|'''Figure 7.''' Anopthalmia
Microphthalmia-500px.jpg| '''Figure 8.''' Microphthalmia
Opac_figure_7.jpg| '''Figure 9.''' Iris Coloboma
Opac figure 10.jpg| '''Figure 10.''' Partial Aniridia
</gallery>

==Future questions==
===Will it be possible to have eye transplants in the future?===
Lots of research has been done in making a whole-eye transplantation successful in order to finally cure blindness. Blindness is a worldwide problem and is currently untreatable due to the fact that retinal ganglion cells and the optic nerves do not regenerate. This can result from diseases including macular degeneration and end of stage glaucoma. The first successful eye transplantation was led by Stone and Cole in 1943<ref name="Return of Vision"> Stone, L. S. & Cole, C. H. (1943). Grafted Eyes of Young and Old Adult Salamanders (Amblystoma Punctatum) Showing Return of Vision. ''Yale Journal of Biology and Medicine, 15''(5), 735-754.2. PMCID: PMC2601300</ref> investigating 104 samples of the salamander species, ''Amblystoma Punctatum'', and one of its eyes were either implanted back into the same animal or it was completely transplanted to a new host. It was reported that circulation in the iris was re-established, retina was able to regenerate, a new optic nerve was connected to the brain through the optic chiasma and ocular movements were regained. Vision was reestablished by the second month. In a more recent study, in 2015, Li et al.<ref name="Structural Integrity"> Li, Y., Komatsu, C., Wang, B., Miller, M., Wang, H., van der Merwe, Y., Ho, L., Kostereva, N., Zhang, W., Xiao, B., Davidson, E., Solari, M., Steketee, M. B., Guo, S., Kagemann, L., Wollstein, G., Schuman, J., Chan, K., Gorantla, V. S., Washington, K. M. (2015). Abstract 112: Evaluation of Viability, Structural Integrity and Functional Outcome after Whole Eye Transplantation. ''Plastic & Reconstructive Surgery, 135''(5), 82. "PMC2601300"</ref> investigated the feasibility of eye transplantation by observing the surviving 15 rat models out of the original 22. They were able to confirm the integrity and functional return of vision after whole-eye surgeries with the aid of advance techniques that are available today. The Ear and Eye Foundation of Pittsburgh<ref>'''Ear and Eye Foundation of Pittsburgh''': https://eyeandear.org/our-research/ophthalmology/the-whole-eye-transplant-project</ref> is an organization that is currently running a project with lead researchers to discover a way for the optic nerves to regenerate and to cure blindness by 2020.

===Will the bionic eye pass clinical trials in the next few years?===
The bionic eye is an external visual device that has been in the making for the last several years. It hopes to bring back full vision through the aid of a pair of glasses with a camera attached to it, which then transmits high-frequency radio signals to the microchip implanted in the users' eye. These signals are converted into electrical impulses by the electrodes implanted in the chip, which then stimulates the retinal cells and passes through the optic nerve. Electrical impulses travels to the vision processing centres in the brain and these are then interpreted as an image. At the moment, users must learn to understand light flashes and visual patterns and convert them into images they can interpret. Current prototypes require the users to have a previously working eyes, which means their optic nerves must still be relatively healthy and their visual cortex must be developed. Patients who have suffered from retinitis pigmentosa and age-related macular degeneration would benefit this technology. Bionic Vision Australia<ref>'''Bionic Vision Australia''': http://bionicvision.org.au/about/research_plan</ref> is one of the leading organisations that are aiming to treat blindness and are set to perform clinical trials on two of the devices of the bionic eye implants soon. Their objectives are to develop strategies that can improve the affected visual pathway to the brain by stimulating the remaining working retinal cells and also develop safe surgical procedures.

==Glossary==

{| class="pretty table"
|-bgcolor = "DDCEF2"
|'''Term'''
|'''Definition'''
|-bgcolor="FAF5FF"
|'''Age-related macular degeneration'''||An eye disease with its onset usually after age 60 that can progressively destroy the macula, the central portion of the retina, impairing central vision.
|-
|'''Aqueous humour'''||A transparent fluid similar to plasma with low protein concentrations secreted by the ciliary epithelium.
|-
|'''Choroid'''||The pigmented vascular layer of the eye located between the retina and sclera.
|-
|'''Choroid fissure'''||A ventral groove formed by the invagination of the optic cup located at the bottom of the optic vesicle through which blood vessels enter the eye.
|-
|'''Ciliary body'''||The connection between the iris and choroid consisting of the ciliary muscle, ciliary processes and the ciliary ring. Alters the shape of the lens and ciliary epithelium in order to focus on an image.
|-
|'''Cornea'''||The transparent anterior part of the external coat of the eye covering the iris and pupil and continuous with the sclera.
|-
|'''Ectoderm||The outermost primary germ cell layer in the early embryo.
|-
|'''Endoderm||The innermost primary germ cell layer in the early embryo.
|-
|'''Ectodermal placode'''||A neurogenic placode consisting of an area of thickened epithelium in the embryonic head ectoderm layer that gives rise to neurons and other structures of the sensory system.
|-
|'''Extraocular muscles'''||Muscles controlling eye movement.
|-
|'''Fovea'''||A small depression in the retina where visual acuity is the highest.
|-
|'''Hyaloid vasculature'''||The temporary circulatory system in fetal eyes which spontaneously degenerate when the retinal blood vessels begin to develop.
|-
|'''Intraocular pressure'''||Fluid pressure inside the eye created through continued renewal of fluids.
|-
|'''Iris'''||The coloured muscular ring surrounding the pupil which manipulates the diameter and size of the pupil and controls the amount of light entering the eye.
|-
|'''Lens'''||The transparent biconvex structure posterior to the iris with the main function of focusing light onto the retina in order to form clear images of objects at various distances.
|-
|'''Lens pit'''||A pit-like depression in the fetal head where the lens develops.
|-
|'''Lens placode'''||The placode developing in the ectoderm overlying the optic vesicle, eventually becoming the lens of the eye.
|-
|'''Lens vesicle'''||The ectodermal invagination in the embryo formed opposite the optic cup and gives rise to the lens.
|-
|'''Lumina'''||the central cavity of a tubular structure.
|-
|'''Macula'''||An oval-shaped pigmented area where there is the largest density of cone cells and is involved in producing the sharpness of central vision.
|-
|'''Mesenchyme'''||Loosely organised embryonic connective tissue originating from the mesoderm.
|-
|'''Neural crest'''||A temporary group of embryonic ectodermal cells.
|-
|'''Neural retina'''||Refers to three layers of neural cells within the retina (photoreceptor cells, bipolar cells and ganglion cells).
|-
|'''Neural tube'''||A hollow tubular structure as a result of neural plate folding which later develops into the brain and spinal cord.
|-
|'''Neuroepithelium'''||Epithelium consisting of specialised cells which detect sensory triggers for reception of external stimuli.
|-
|'''Optic cup'''||A structure of the diencephalon formed after optic vesicle folding. This structure gives rise to the retina.
|-
|'''Optic groove'''||Two small grooves on each side of the developing forebrain in the neural folds. Also chiasmatic groove.
|-
|'''Optic nerve'''||Cranial nerve II which transmits impulses to the brain from visual information detected by the photoreceptive retina.
|-
|'''Optic stalk'''||Pair of slender embryonic structures that give rise to the optic nerve.
|-
|'''Optic vesicle'''||An evagination of each lateral all of the embryonic vertebrate forebrain from which the nervous structures of the eye develop.
|-
|'''Pupil'''||The central opening in the iris, allowing and regulating the entry of light into the eye.
|-
|'''Retina'''||The sensory membrane that forms the inner lining of the eye containing rods and cones with the main function of photoreception. Nerve impulses in response to visual information are transmitted to the brain via the optic nerve.
|-
|'''Retinitis Pigmentosa'''||A chronic hereditary eye disease characterized by breakdown and loss of cells in the retina leading to progressive visual loss.
|-
|'''Sclera'''||The dense, white, fibrous membrane that, along with the cornea, forms the external protective covering of the eye
|-
|'''Tear film'''||A layer of tears which spreads over the eye, ultimately maintaining the health of the ocular surface by making the external surface smooth and clear.

|}

{{Glossary}}

==References==

<references/>

==External links==

<pubmed>26956898</pubmed>

Talk:2017 Group Project 6

2017-10-12T05:28:33Z

Z3416557:

{{ANAT2341Project2017discussion}}



=Project Starting Places=
[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 10:15, 14 August 2017 (AEST) OK Group 6 below are some starting places.
=What to improve from peer reviews=
z5076158 Tick off once this has been adjusted:
*Future Research Questions heading
*Split up adult and embryo anatomy under heading “basic anatomy”
*Break down development – use dot points for types on grey matter etc, first paragraph is a big block of text – subsection it
*Key historical discoveries – add images
*Current research heading
*Change the blue title
*Basic anatomy – talks about development, move it to that heading
*Cerebellum development table takes up a lot of space
*Pictures in second trimester section of table
*Neural development heading moved to cerebellum development
*Caption photos placed together for abnormalities section – make photos look neater
*Move timeline to before the info about development
*Key historical discoveries – use a table with 2 columns – name of discoverer and brief description
*Improve on cell signaling in cerebellar development (bit length), key discoveries and animal models, make them more engaging with photos, videos etc.
*merge the introductions
*add images to microanat
*don’t centre text for cerebral nuclei table
*place info about primary and secondary vesicles above their images
*introduction repeated the word ‘hence’ too much
*look over reference list – some were just links
*references for weeks 3-6 on developmental timeline
*repeated references
*student drawn diagrams!
*link other wiki page entries
*utilize videos
*Include symptoms for abnormalities
*Include a glossary
*References found in the reference list found inconsistent and not in style (2 – 5, 10 – 13, 17, 18, 30 – 32) , 47 and 48 are duplicated
*In the early brain vesicle and abnormalities section, diagram’s description should be put in the file link under “alt text” so that they appears underneath their images instead doing it separately, this includes figure 6.
*Microanatomy should be linked in with anatomy section
*Isthmic organizer – section seemed out of place
*Complications of abnormalities could be added

{{Neural Links 2}}

PubMed Searches: [http://www.ncbi.nlm.nih.gov/pubmed?term=Cerebellum+Development ''Cerebellum Development'']

BMC Dev Biol Search: [http://www.biomedcentral.com/bmcdevbiol/search/results?terms=Cerebellum+Development ''Cerebellum Development'']

Cerebellum: links between development, developmental disorders and motor learning; [http://journal.frontiersin.org/article/10.3389/fnana.2012.00001/full]

Cellular commitment in the developing cerebellum [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4290586/]

Recent papers

<pubmed limit=5>Cerebellum+Development</pubmed>

==Neural Development==
(z5114433)
will fix referencing stuff later #ceebsrn

Neural development is one of the earliest systems to begin and the last to be completed after birth due to its highly complex structure. The first step in neural development occurs at the end of week 3 and involves the folding of the neural tubes to form the cranial and caudal region of the embryo (''https://discovery.lifemapsc.com/library/review-of-medical-embryology/chapter-26-embryonic-folding-and-flexion-of-the-embryo'') . There is a high chance of neural dysfunction and defects during the fetal neural development particularly due to the long development time frame and the need of certain nutrients such as folic acid to successfully close the tubes. Neural tube defects (NTDs) such as [[spina bifida]] and [[anencephaly]] can arise if the tubes do not close effectively.

=z5114433=
structure
time course
functional developing
what cells appear when

glial cells development

4th ventricle

Genes in abnormalities

pathway of development of cere cells
start of as neuroblast

=z5018156=
Things to remember:

Coordinates muscular activities - walking, crawling, writing

Embryo doesnt need the musuclar activities

Prenatal - neurons develop to carry out those activities later on

Postnatal - wiring up

Neural tube

Comes from pontine flexure - 4th ventricle -- the cerebellum develops into this space

Lamination of the cerebellum

https://www.ncbi.nlm.nih.gov/pubmed/19732611

https://www.ncbi.nlm.nih.gov/pubmed/21380713

Development: z5018156 - https://www.ncbi.nlm.nih.gov/pubmed/21295689

=Z5076158=
==Week 7 Work==
What I could add: Paramotal cells, molecular layer, what cerebellum connects to, how they are remodeled postnatally Kahals research
https://discovery.lifemapsc.com/library/review-of-medical-embryology/chapter-150-the-brainstem-metencephalon-fourth-vesicle-the-cerebellum - good reference
LARSONS HUMAN EMBRYOLOGY TEXTBOOK
The metencephalon gives rise to the pons and the cerebellum, the adjacent rhombic lips also contribute to the development of cerebellum. The pons functions to relay signals that link both the spinal cord and cerebral cortex with the cerebellum and the cerebellum is a centre for postural and balance control. Pontine nuclei relay information from cerebrum to the cerebellum.
The cerebellum is first recognized as a pair of thickened cerebellar plates or cerebellar primordia.
Adjacent rhombic lips gives rise to Cerebellar granule cells
Major portion of the cerebellum consists of a narrow median swelling called the vermis and this grows faster than the flocculonodular which were the primitive part of the cerebellum and therefore becomes the dominant portion of the mature cerebellum.
Folding:
Primary fissure deepens by end of third month and divides vermis and hemispheres into a cranial anterior lobe and caudal middle lobe. Lobes divide further into lobules due to development of transverse fissures. This fissure formation and foliation continues throughout embryonic, fetal and postnatal life and this is done to increase the surface area of the cerebellar cortex.
2 types of grey matter present:
- Internal deep cerebellar nucler
- External cerebellar cortex
4 deep nuclei and all output of the cerebellar cortex is relayed through these nuclei.
These nuclei and cortex are produced by a process called neurogenesis and neuronal migration
1. Dentate
2. Globose
3. Emboliform
4. Fastigular

4th month – germinal layers undergo cell division and this produces populations of cerebellar neurons.
• Ventricular layer – purkinje cells, golgi cells, basket cells, stellate cells
• Granule cells remaining from the cerebellar cortex (these arise from external germinal layer)
• External germinal layer – primitive nuclear neurons these migrate to form deep cerebellar nuclei
==Week 8 Work==
PAPER 1995
Cerebellum – about:
It consists of 3 layers with 2 principal classes of neurons
Granule cells studies of naturally occurring mutations and targeted gene disruption that block discrete steps in development of this region
Development of anterior portion of neural tube involves the formation of 3 brain vesicles:
1. Prosencephalon
2. Mesencephalon
3. Rhombencephalon
Division of rhombencephalon into metencephalic vesicles and myelincephalic vesicles (this forms in day 9)
Failure of neural tube closure creates gap along the dorsal aspect of the neural tube, which bows into a mouth-like structure as the tube bends to establish the pontine flexure.
Further deepening this newly formed pontine flexure, bringing the mesencephalon (midbrain) closer to the primordium of the cerebellum (metencephalon); anterior aspects of the myelincephalon (brainstem) fold underneath developing the cerebellum plate.

Cells fated for cerebellum are derived from both the mesencephalon and metencephalic vesicles (rhombencephalon). Neuroepithelium of the mesencephalon generated majority of the cells in the cerebellar cortex: V-like area of mediodorsal aspect of the anlarge arose from a caudal movement of cells from the mesencephalon.

PAPER 2014
Cerebellum has a very basic structure:
• Monolayer of inhibitory purkinje cells sandwiched between a dense layer of excitatory granule cells
• Subpiled molecular layer of granular cell axons and purkinje cell dendritic fibres
Granule cells receives inputs from outside the cerebellum and project to the purkinje cells, the majority of which then project to a variety of cerebellar nuclei in the white matter.
The area designated for the cerebellum to reside (anlage) during development was located between hindbrain and midbrain. Regulation of patterning in this early stage (E9) of development shows to be particularly important for development of the uniquely mammalian midline expanded region of the cerebellum, “vermis”.

Specific cell types are allocated along the dorsoventral axis. For glutamatergic cells of cerebellum, remarkably prolonged establishment and an important dynamic process that takes place at most dorsal interface between neural and non-neural roof plate tissue, the rhombic lip. This phase generates the basic dichotomy between GABAergic and glutamatergic cell types that underlies the conserved Purkinje-Granule cell circuit.
Cell type allocation proceeds a third, distinct temporal phase of development that extends into early prenatal (up to 2 years). In this phase, the principal derivative of the rhombic lip, the granule cell precursor, accumulates over the surface of the cerebellum and undergoes further rounds of symmetric division in a process of transit amplification that exponentially expands its numbers.
The anlage of the cerebellum is a product of mechanisms of segmentation that establish iterated rhombomeric subdivision within the hindbrain just after neural tube closure.
All cells of the cerebellum arise from dorsal rhomomere, a region definitively classified by absence of the expression of Otx and Hox genes. Majority of cerebellum arises from metencephalic (rostral) hindbrain.

=z5113034=
Vasculature of cerebellum originates from vertebral arteries and the arteries that arise from it.

Metencephalon; temporary structure that differentiates into pons and cerebellum ventrally and dorsally respectively.

Current Research

Key discoveries during research of cerebellar development

=Topic Selection=
Hi group! I am personally interested in the development of the heart! Also, are you guys happy to exchange details after the lab tomorrow? - z5018156

Hi! Im happy to share details! And yeah heart would be interesting, but I was also thinking maybe the ear? that could be cool

Hey, yeah I was thinking the heart- I did a course on it last semester, but i also feel its quite generic and the other groups would do something similar. Shall we wait until the end of prac and find each other? Call out number 6 LMAO (z5114433)

Hey all! I'm pretty open about topics but I was leaning towards the eye? Unless that's too close to optom, (and it might be a popular subject too?) I'm fine with anything. Let's find each other after prac! -z5113034

The ear sounds good as well as the eye, theres also the lungs as well! We can just make a list and then decide as a group! - z5018156

=Peer Review=
This page is very informative, well set-out, and easy to follow and read. The information is well-referenced and the images have a description, the correct Copyright, however some lack the appropriate Student Image template. The "Key Historical Discoveries" and "Cell Signaling in Cerebellar Development" sections could be broken up with relevant images. Other images I find are too large and could be made smaller. The smaller amount of information above the "Introduction" would flow better if it was all included as one introductory paragraph. The images in the "Abnormalities" section could include a small description directly under them to describe the image and make it more uniform with the other images on the pages. Reference list is extensive and done very well. The page could be improved by including a "Future Research Questions" section. Overall very hard to fault!

---

The information is really well written and informative. The use of images is really good, especially with the description and when they have been included in the table. The section on the Historical Discoveries is a really interesting part and adds a good amount of background information to the cerebellum. Maybe add a table for the glossary section part that just relates to the terms relating to the cerebellum. Make sure that all references are referenced properly, not just the addition of the links. Overall, a really good wiki and the information is understandable and very well done.

---

*This page was easy to follow and had relatively good flow, with relevant headings and subheadings relating to the development of the cerebellum. There were some sections under Anatomy of the cerebellum relating to the development (see Neural Development) which seemed out of place, so I suggest to put it under the Development section to improve flow.

*Basic anatomy of the cerebellum contained a good amount of information, which provided relevant background knowledge before jumping into the development.

*Images were nicely chosen and was very relevant to the content, and they were also cited properly. Perhaps you could add in some images in the table of Cerebellar Nuclei to make it easier to visualise.

*The section Cerebellum is informative but too wordy, making it difficult to read through. Adding in a couple of images in between points would making it easier to read and understand.

*The table of "Cerebellum Developmental Weeks” First Trimester was nicely done as it was simple and easy to understand, and had relevant images to visually aid the reader. Perhaps you could add in images in the Second Trimester table to balance it out.

*There is a vast amount of references used, and they were done properly.

*A "Further questions" section is needed to address any research gaps as well as explore more information on the Cerebellum. So far, well done!

---

There is a good introduction into the cerebellum which is also connected to the page and what the page will explore. The “basic anatomy” subheading is nice and succinct with minimal text and clear diagrams that clearly represent the anatomy of the cerebellum. The “Vasculature” subheading also provides a good overview with a simple diagram to complement. The only thing I find a bit odd about all the subheadings under “basic anatomy” is that I feel as though we go from the adult human anatomy of the cerebellum into embryological anatomy of the cerebellum. I think it might serve you better to split these up or just rearrange/rename your subheadings a bit. The reason for this is because the cerebellum is quite complex so I think it would help to absorb the information.
The “cerebellum development” is a good and descriptive subheading with a good use of diagrams. Since there is quite a big chunk of text, it would probably be better if you broke it down where you could. So, for example, where you say: “there are two types of grey matter in the cerebellum…” you could easily use dot points. It just helps with readability.
The “cellular migration” subheading is very good and the diagram you found is a great representation of it. I like that you added images to complement each week of development in your first trimester timeline. If you can do the same for your second trimester timeline that would be great. Your “key historical discoveries” subheading could use some images (even if it is of the people who made the discoveries). You chose a good number of abnormalities to explore in that last section. You might want to add another section for “future questions” just to hint at what more we need to learn about cerebellum development. You have a solid, long list of references.

---

Really good project page. The page goes through almost everything required for the project. You need a section about Further Questions and Current Research. The project is really well written and easy to understand. There is a good introduction giving the reader an idea of what to expect from the project page and good use of pictures giving a basic understanding of the anatomy of the cerebellum. There is a lot of use of figures and tables, which makes it easier for the reader to understand the subject. Most of the figures have a figure number and text, this also makes it easier to get a quick view of what the text refers to. The layout of the page is also comfortable to go through, but I do think the title Cerebellum in blue is a bit disturbing. There is good use of references.

*It seems like you have mixed the context in '''Basic Anatomy of the Cerebellum section''' and the '''Cerebellum Development'''. During the 'Anatomy section, you start describing the developmental origin, which I think would fit better in the Developmental section.
*The first section in the '''Cerebellum Development''' has a lot of text. Maybe you can make some subsections to split of the text and makes it more comfortable to read.
*The '''Cerebellum Developmental weeks table''' is really good and has good use of pictures. But the format makes it really big. Maybe you can do this part in a different way, so it does not take that much space. For the table about the second trimester, it would be a good support for the reader to add pictures to this table too – like the first-trimester table.
*The '''Key Historical Discoveries''' has a lot of text. Maybe you can add some pictures or change the layout a bit.

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Very efficient page in its structure and attention to detail throughout the text. Subheadings are easy to follow and did not cause any confusion. The use of diagrams and images are relevant and accompany the text well and are referred to as figures which elevated the efficiency, however, inconsistencies in labelling the images are evident with many images lacking the figure number such as “diagram of a 2 day old…”. This would ease the process of referring to images throughout the writing and improve the reading experience. There is no section on current research or further questioning which is a shame as it is an interesting aspect of reading these pages and I feel it would add an up to date relevance to the overall page. Expansion on the abnormalities mentioned under the subheading is required as only a few are mentioned and not discussed. Some of the technical terms were difficult to follow so definitely a glossary would fix this. Referencing seems to be quite consistent throughout for the most part, however some areas are lacking acknowledgement to resources. Overall, an informative page which demonstrates a thorough understanding of the cerebellum.

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Overall, this team's wikipage was really informative. They were detailed yet not too much information was given. There was a good balance with text and pictures. The pictures chosen were all of good quality as well with appropriate description, referencing and copyright information provided. The introduction was a very good brief of the entire page and explained what was to be expected. In the basic anatomy of the cerebellum, the subheadings were really well-defined. However, maybe neural development should be shifted to the developmental section instead. This section was well referenced. I like the use of the table to describe the cerebellum developmental weeks. The images used were really helpful in visualizing what was happening in those weeks. In the abnormalities section, it was short and concise with good picture. Maybe the caption of the photos could be placed together with the photo such as those in the table. This could make the photos look neater. Overall I find that this wikipage was well done, it had a good amount of text and photos and the references were all properly included.

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Overall, I think this project page is really good and well done to the team. I think the headings and subheadings flow easily and there is a good arrangement of information. There is a good amount of referencing and the images have copyright statements and brief descriptions. For the “Neural Development” subsection, instead of placing it under the anatomy of the cerebellum, I think you should move it down to the development section as it has more relevance to that. I think the Cerebellum Developmental weeks should be shifted to before the description on cerebellum development. This way, the readers can have a general idea on the development and its stages before going through he description because the description is quite content heavy and if we were to read that first, its quite confusing and hard to understand. For the key historical discoveries, maybe you could use a table with two columns where one column can be the name of the discoverer and the other column could be a brief description. The abnormalities section was done well.

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Overall this project is very extensive and appears to almost be complete. The structure and lay out is clear and easy to follow. The numerous tables and diagrams are very engaging. The material seems to be relevant, informative and well-referenced. I think the you could combine the first section into the introduction as it is confusing to have two introductory sections. Also the blue title could be larger and at the top of the page to highlight the overall topic of the project. The sections of ‘cell signaling in cerebellar development’ and ‘key historical discoveries’ and ‘animal models’ are not very engaging to read as they are just large chunks of text and perhaps images, videos or collapsible windows could be used to break them up and make them more attractive. Despite these minor suggestion, your project is extremely well done!

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The introduction and the information above the introduction is really good, however, I think it would be better if you merged these into one as it sort of seems like two introductions and doesn't flow very nicely, even though what you're saying is really good. The basic anatomy was really good, especially with the images and the reference to them. The microanatomy information is good however would be better if you added images like you did in the anatomy. The cerebral nuclei table is good, however, I think its distracting the description in the centre, just have it normal and don't centre your text. Place the information about the primary and secondary brain vesicles above their images and then refer to the images. Some of your sections, for example, cell signalling or key historical developments, are really wordy and hard to keep a focus so maybe split them up with images, videos, or tables. The rest of the page looks really good, maybe just add some more information to the abnormalities as some are only a sentence or so. The page could also benefit from using a video or two. Referencing is good.

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It was really good that the structure and function of the cerebellum was explained in a succinct way in the beginning. The introduction repeated the word 'hence' a few times, maybe it's better to modify it into bullet points, in a similar way when lecturers provide a slide on the lecture overview. Appropriate images were added as well as figure labeling. Copyright approval was also provided for the images and were referenced appropriately. The use of tables was also appropriate in some of the topic sections. Images were also in appropriate sizes that avoided covering the while page. The page was very detailed as well. Some sections like "Cell Signaling" was a bit lengthy, images would be nice. It was good that reputable journal articles were used for the project, proper in text citations superscripts were also done properly. However, revise the reference list because some were left as links and the list did not have a consistent reference format. But overall, the page looks almost complete.

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This page seems to have the one of the best organizations. All the sub headings needed for the project are included and completed (minus further questions). The introduction is a nice addition as it gives a roadmap to your page. The entire Basic Anatomy is informative and sectioned nicely into the most important topics--some of the images may be a bit too large however. I like that the information for the first and second trimester is separated, instead of clumping it all together. Cerebellum development, cell signaling, and key historical discoveries have a lot of text and might need some diagrams or tables to break up the text. Also it would help to put the key historical discoveries at the beginning so that the reader knows how it led to the information we know today. The neural development section should be moved below microanatomy and before early brain vesicles since it leads into that section. The

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This peer review is based on the relevant dot points of the ‘Group Assessment Criteria’, as well as subheadings suggested by Mark. This information can be found on the student page.

{| border="1" align="left"
|-
|Criteria
|Strengths
|Weaknesses
|-
| 1. The choice of content shows a good understanding of the topic area
| The ‘basic anatomy of the cerebellum’ section is written well and in detail. It provides a solid introduction to the wiki page, as well as background information that assists in understanding other sections. The chosen visual aids enhance the written information, and allow the reader to visualize some of the more complex ideas.

The ‘signaling processes’ and ‘key discoveries’ sections were both well addressed, with the information being expressed clearly.

The developmental timeline provides a nice summary of cerebellum development, especially throughout the first trimester. The accompanying images are both relevant and useful in understanding the text.

Overall, the wiki page is structured well, with the chosen sub headings making the page easy to navigate.
| The wiki page lacks some important areas of information, including:
*‘Future questions’ regarding development of the cerebellum
*‘Current research’ in relevant fields
*A glossary of terms

Some sections could also be improved. The ‘animal models’ section has been addressed minimally, with only one example being provided. Try to include several more examples of animal models. In addition, the ‘abnormalities’ section lacks detail for some of the examples (see ‘rhombencephalosynapsis’).

Some areas of the wiki page would benefit from visual aids, such as the ‘animal models’ and ‘signaling processes’ sections.
|-
|2. Content is correctly cited and referenced
|Most areas of the wiki page contain some degree of referencing. ‘Cell signaling in Cerebellar development’ was the most well-referenced section.
The reference list is extensive and is mostly correct. The majority of the sources in the reference list are peer-reviewed primary research articles.

Most of the images on the page have been referenced correctly (see all images in the ‘abnormalities’ section).
|Referencing throughout the wiki page is inconsistent. Some areas contain minimal in-text citations (see ‘cerebellum development’) and other sections lack referencing entirely (see weeks 3-6 of the developmental timeline). Remember to cite any and all text that is unoriginal in regard to idea or structure.

Some of the images on the wiki page have not been referenced correctly (see ‘lateral view of embryo central nervous system at 5 weeks’). In addition, the copyright section of figure 4 states that ‘copyright has been requested’; avoid uploading images until after the copyright request has been approved.

Some references have been repeated in the reference list (see references 47 and 48).
|-
|3. The wiki has an element of teaching at a peer level
|The information presented on the page is written at a level suitable for peers.

Many of the chosen images and tables help clarify some of the more difficult concepts discussed on the page.
|Many of the acronyms and terms used in this assignment are either poorly explained, or not explained at all. Remember to include relevant definitions in the ‘glossary’ section of the page.

The page currently lacks student-drawn diagrams; try to include some for the final submission (and remember to cite the source of inspiration).
|-
|4. Relates the topic and content of the Wiki entry to learning aims of embryology
|The wiki page addresses most of the relevant learning aims of embryology, including embryonic development, a developmental timeline, signaling processes, key discoveries, animal models and congenital abnormalities.
|There are some sections relevant to the learning aims that have not been included, such as ‘current research’ and ‘future questions’.
|-
|5. The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic
|Most of the content on the wiki page has been researched well, particularly the ‘basic anatomy of the cerebellum’ and ‘cerebellum development’ sections.

The reference list contains a large variety of reliable sources of information (i.e. primary research articles). This demonstrates that this topic has been well researched.
|Links to other wiki pages on the UNSW embryology wiki have not been included. Try linking some sections of the page to other wiki entries, such as ‘lecture 4 – week 3’ or ‘lecture 5 – ectoderm’.
|}
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Strengths: 
• The authors of this wiki page have included a variety of topics relevant to the development of the cerebellum. Topics range from the normal anatomy of the cerebellum, abnormalities, and the normal developmental process to animal models. Thus it is evident that criteria 1 has been satisfied which is excellent! 
• A broad variety of tables and images have been utilized within this wiki page which is another excellent feature that has been included. Not only has this enhanced the presentation of the page, but the images serve as a visual aid in assisting in the explanation of certain concepts to peers (particularly those who are visual learners) (criteria 2 and 4 satisfied). For example the use of images was utilized to help simplify the explanation regarding the vesicles that development. 
• It also appears that authors have included a broad variety of references in-text to cite all information utilized. Most source utilized appear to be recent and all have been correctly cited (criteria 3). 
• The authors of this page have also explored evidence of significant research relating to basic and applied sciences that extends beyond the formal teaching activities (criteria 5) by exploring avenues including animal models and how the use of animal models have contributed to our understanding of the cerebellum. Authors of the page have also explored abnormalities of cerebellar development which was excellent 
Areas of improvement: 
• In order to improve, authors may wish to expand on different animal models utilized.
• The authors of this wiki page may also wish to utilize videos as another visual tool to aid in the presentation of content included. 
• Another area of improvement would be to cite sources that are of a more recent date, rather than citing sources from the 1970s. The reason being is that such sources may include information that is currently outdated, thus the page may be providing inaccurate information about cerebellar development. 
• Authors of the page may have also covered certain topics in greater depth. For example the heading titled “Cell signaling in cerebellar development” may have been subdivided into different types of genes and signaling factors involved in cerebellar development. Authors may then elaborate on each gene/signaling factor. This will help enhance presentation whilst also improving the readability of the information presented.

Grade: DISTINCTION

General Comments:
Most sections of this wiki page have been presented at a high standard. There are only a few areas that could do with some improvement.

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'Basic Anatomy of the Cerebellum' has really useful and clear diagrams that support the content. However, the content was a bit brief in this section. All easy to read and follow. 'Early Brain Vesicles' has useful diagrams but needs more text to back them up. 'Cerebellum Development' is well written and referenced with appropriate diagrams and captions. 'Cerebellum Developmental Weeks' has very brief descriptions; needs to be more detailed and the pictures better explained or better captioned. 'Key Historical Discoveries' are interesting and well referenced. 'Ramon y Cajal' might need to be corrected to 'Ramon and Cajal' if reference is in Spanish.. Maybe add some pictures to this section too. 'Animal models' could use more subheadings and more examples of animals models as there is only currently one described. 'Abnormalities' has interesting pictures and examples but is a bit brief in its descriptions. Overall, interesting topic and well used pictures. Some sections still need work; Glossary and maybe add a 'Future Research' topic to the page. Also a requirement of the project is to include one hand-drawn diagram which has not yet been added.
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'''Peer review project 6:'''

* Overall the project was good and had both a abnormalities, animal model, timeline, signalling and development origin section. It does not have a current research and question for the future section.
* I like the timeline. It was nice and easy to read and gave a good overview over the developmental process. I like the use of embryonic pictures. Maybe instead of having a key historical discoveries section it could be integrated in the timeline?
* Good selection of pictures and the picture have caption. But the caption does not following the protocol.
* The abnormalities could have more context to it.
* I think it would improve the project if the timeline where before the developing process because then you read the table, get an idea about what is going to happen and then you can read the steps in detail. The developing process section could use some more breaks and pictures to make it look a little less dense.
* In general, good referencing but some sections like purkinje/pyramidal cells miss their reference.
* The anatomy section was good and informative

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The appearance of the project page is really good and the content is well written and very extensive on the Cerebellum. The balance of text to pictures is generally good, however I do think the section on the on ‘cerebellum development’ is maybe a little too wordy and could be broken up with more pictures/ animations, or could be cut down. The pictures that have been chosen are of high quality from appropriate sources and well referenced. I found the ‘cerebellum developmental weeks’ particularly clever as a way of putting this information across, greatly helped by the accompanying pictures as a visual aid. I do not think that the title at the top needs to be in blue, as it doesn’t seem to fit with the general theme. I think a ‘future research’ section would be particularly helpful to address any exciting new developments or the focus of recent studies. I do however think you have done a really good job so far, well done

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Cerebellum GROUP Project 6
- I like how it first introduces cerebellum as an organ and progresses to describing what will be discussed in the page in a nice summary for the introduction. It also described what type of things to expect on this page which is a nice way to introduce the project

- I like how the pictures have a small description underneath to describe what the picture is talking about and it was also referred to in the text

- Anatomy was very detailed and also included small details such as including vasculature as well which I liked

- Microanatomy was divided into clear subheadings to describe different type of cells in cerebellum, but possibly lacking some references in a few places for this section.

- Table of the type of cerebellar nuclei was useful and a picture of the location of nuclei would’ve made it even better

- Nice division of early brain vesicles into primary and secondary and also describing metencephalon. Including description about the other brain vesicles is needed as well

- Cerebellum development paragraphs could be divided more so that it easier to read instead having it as a large chunk of text. Other than that great explanation of the development and very detailed.

- Cellular migration picture was very nicely used in this section and helped explain granule and purkinje cell migration

- Cell signalling was covered well but maybe dividing up the text and adding some photos will help distribute text in a way so that its easier to read

- Cerebellum developmental week table was nicely done with images for each stage of neurulation which correlated well with the description of the weekly development. Maybe could’ve rearranged the images and text so that it isn’t too spaced out

- I liked how you have also included key historical discoveries which was rarely seen in most of projects.

- Abnormalities was well done but could do with some more detail into each abnormality and possibly include symptoms as well for some of the abnormalities

- Including the glossary would’ve made it better, referencing was well done and detailed and good use of reliable source

- Overall, a solid page with a detailed amount of information for each subheadings that is well written. Fixing up the details I have pointed out will make it a great project.

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This page starts off nicely with a brief introduction. The page looks almost completed with well written texts and diagrams, are referenced thoroughly but inconsistent in some part in the cerebellum development week 3 – 6 . They have covered most of the requirements, just the current research and findings are missing, would be beneficial if you include them. The abnormality section has good amount of texts and pictures for each one, mention a few more of abnormalities if available. The animal model lacks images. References found in the reference list found inconsistent and not in style (2 – 5, 10 – 13, 17, 18, 30 – 32) , 47 and 48 duplicated. Include glossary terms in the glossary section. In the early brain vesicle and abnormalities section, diagram’s description should be put in the file link under “alt text” so that they appears underneath their images instead doing it separately, this includes figure 6.

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* Microanatomy
** Should be moved upwards and linked together with anatomy
*Cerebellum development
** Section felt long and overly-packed. Could benefit from better formatting or use of appropriate subheadings to divide information into more easily digestible parts
* Isthmic organiser
** Section seemed somewhat out of place, should consider moving this section somewhere
* Abnormalities
** Complications of abnormalities is an area that can be discussed to enhance content
* Overall, good effort and well written page. However:
** Some diagrams lacked descriptions and figure legends/abbreviation definitions – diagrams should be self-explanatory and be understandable in combination with their descriptions, when taken out of their contexts within the page
** Minor grammatical errors present throughout the page
** Remember to remove zIDs before final submission

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I think overall, this project is the most wholesome and well formatted. You have provided a great deal of information, which you have supported with many relevant references. It is clear that a lot of effort has been put in - well done. At times there is a lot of content, e.g. cerebellum development section, but it is fine because your language is plain and under stable and you have provided suitable diagrams. Perhaps adding a video could be a good addition. Your first trimester table has good detail and is easy to understand, however I would suggest changing the colour scheme of the table because it was a bit hard to differentiate the rows and looked like there was just a huge white space with words in the middle. Nothing that can't be easily fixed though. Same for the table under it. I think you have good flow to your page, however I would suggest changing the size of the subheadings in the abnormalities section because they're all the same, so got a bit confused at first.

Overall very well done.

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*I personally think that this page is the best out of all six groups. Content is generally good with clear elaborations and labeled figures that are essential in explaining the anatomy and development of cerebellum. Figures are well labeled and clearly referenced.
*Although the content has been properly referenced in the text, the group may want to decide on one style of referencing i.e. APA or BJP for reference list.

__

Group 6

Introduction: I think this is a good idea but I would try and make it a bit more concise/general Basic Anatomy/Microanatomy: I like the way you have described the anatomy through description of pictures - it is very clear to understand and i think it is well categorised with an apt amount of information on each section Vesicles/Cerebellum Development: there is a great amount of detail in this section but I would work to make it more readable especially with the large chunks of text in the cerebellum section Cell Signaling: this section is well categorised and well referenced Timeline: good use of images here

Overall: a well researched a referenced page. Only comments would to try to make some sections concise and consider how each section flow into each other

Talk:2017 Group Project 5

2017-10-12T05:28:03Z

Z3416557: /* Peer Review */

{{ANAT2341Project2017discussion}}


==Suggested Starting Places==
[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 10:15, 14 August 2017 (AEST) OK Group 5 below are some starting places.

{{Respiratory Links}}

PubMed Searches: [http://www.ncbi.nlm.nih.gov/pubmed?term=Lung+Development ''Lung Development''] | [http://www.ncbi.nlm.nih.gov/pubmed?term=Respiratory+Development ''Respiratory Development'']

BMC Dev Biol Search: [http://www.biomedcentral.com/bmcdevbiol/search/results?terms=Lung+Development ''Lung Development'']

Recent papers

<pubmed limit=5>Lung+Development</pubmed>

=Peer Review=
This paper is divided into logical categories and has very good layout. The student drawings are all good, and the developmental timeline is very informative. Most images are well-referenced and have the appropriate Copyright, except the images in the 'Developmental signaling processes' section which lack a description and Copyright. The "Structure of Respiratory Network", "Developmental signalling processes", "Research" and "Animal models" sections of the page lack in-text citations and thus lack credibility.

The use of movies is very clever and helpful provided using content off the UNSW Embryology Wiki page is permitted. The layout of the entire page is very good, however the size of some of the images needs to change as they appear pixillated and blurry. Images could include a small description directly under them to direct the reader to what they are looking at. The references need to be fine tuned, and some grammatical errors need to be addressed. This page would benefit from a lengthier introduction leading in to lung development and a glossary list. Otherwise this is a very informative page!

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Future questions and current research subheadings are incomplete. Don’t forget to add references, copyright statements and the student image template to each of the images that have been used on the wikipage. References should be used on Lung Histology to show the research that has been done. The animal models section is comprehensive but there are barely any references to show where the information was found.

Subheadings and content that have been used show a good understanding of the topic area. The team have used their own images to show their understanding. The team has used images in the ‘Developmental timeline’ table which shows comprehensive research. The images have brief descriptions below them, hence readers will be able to understand what the image is displaying. Important words in relation to the lung have been bolded. The abnormal development section is done comprehensively with references and images. References were cited properly, however there is an error on reference 20.

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The project page is looking good. I particularly found the developmental timeline to be very informative and easy to follow. I like the fact that you have used a table here to display it along with diagrams that fit each stage, with each diagram being cited and referenced correctly.
I think the diagram that is related to the histology section could be a little clearer to read as it is a little jumbled and slightly hard to distinguish everything.
The section on developmental signaling processes is good, and gives the detail without making the section too long and complicated.
‘current understandings and areas of research’ has no information as of yet, it would be good to add some recent research papers with a short summary.
The use of movies is helpful, but maybe consider moving them further up the page, to a more relevant section, the beginning of ‘developmental origin’ would be better.
A glossary of terms would be helpful, as some of the jargon is complicated.
There seems to be a citing error in the reference list that should be dealt with.
Overall it is a very interesting topic and I think you have executed it well so far

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The page is quite informative, however there are incomplete sections including the introduction and the last few topics towards the end. There is a clever use of self drawn images to avoid any copyright issues, but the lung histology image can be a bit hard to read due to the lack of contrast (the grey outline and font being a bit light to read) and the image itself is bit unclear (Is it a lateral view? cross sectional? towards the apex of the lung?). The bolding of main terms at the start of the page is a nice touch, it would work better if there was a glossary at the end of the page stating the bolded terms and their meaning. It would also be better if the rest of the page had their main terms bolded as well and added to the glossary. The movies section seemed a bit out of place and did not flow from the previous and next topics, it would be better to move them into the "developmental" topics. In the abnormal development and animal models sections, more images that correlate to each subheading would be advised to help the reader visualise the abnormalities or results instead of reading chunks of words. Such images could include x-rays, images of physical observations of sufferers, graphs and figures. Development of the lungs topics were easy to: follow, read and understand, which is extremely important. Ref 22 isn't stated properly.

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The project has a very good lay-out and is written relatively clearly. The table with the developmental timeline and historical discoveries of those developmental stages is excellent and the images that go along with each stage are relevant and have a summary and the appropriate copyright information when you click on them. Some pictures on the page do not have the appropriate copyright information or a summary of them when clicking on them that still needs to be added. In-text citations need to be added to a lot of the sections. There are 7 in-text citations at the beginning of the references section that do not refer to any specific information that should be moved to the appropriate information.

The information in the project is good and you explain studies that have been done to determine this information throughout the project which is an effective way to describe past and current research. There is currently no information under “Current understandings and areas of research” and “Future questions,” but these headings could potentially just be eliminated.

The project is relatively clear but a couple things could be added, changed, or moved to add more clarity. There are some basic grammatical issues and spelling errors that can easily be fixed (e.g. “These branching structures involve are regulated by a network of signalling factors”). In “Developmental signalling processes,” adding whether each signalling molecule is either a ligand, receptor, or transcription factor (e.g. Sox9 is a transcription factor, SHH is a ligand, and HS-GAG is a receptor), what cells these molecules are expressed in, and which cells these molecules act on (if different than where they’re expressed) may make this section clearer. In “Animal Models” the introduction of mouse models would make more sense if there was an explanation of the mice used in the studies (i.e. what strains of mice are used, how are they genetically modified, do these mutations result in a KO, etc.) rather than just the genes being looked at.

Overall good project. Referencing needs to be fixed, summary and copyright information needs to be added to some pictures, and blank subheadings either need information or should be eliminated. The information in the project is good, the lay-out is good, the interspersed information about research is good, and the pictures support the information well.

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*This page is very informative, the headings and subheadings were highly appropriate and made the development process much easier to follow.

*I liked how you provided the Anatomy, Histology and Vasculature of an Adult Lung, which provided a good amount of background knowledge before exploring the developmental process. Perhaps you could label the images with “Figure 1/2/3 ...” so you could easily refer to them in-text, such as “Figure 1 shows the anatomy of the adult lung” instead of “This diagram shows the anatomy of the adult lung”. Although this section was very informative, it seems to lack references.

*The table on the Developmental Timeline was perfectly done, as it ties in the development with historical discoveries and had appropriate images to provide visual aid. Furthermore, this table has a good amount of references on it. Well done!

*Although most sections were cited correctly, there is quite a few sections which did not have references at all (see “Structure of Respiratory Network” and “Lung Anatomy and Histology”) so it would be good to add them in to avoid plagiarism.

*A good amount of images were used (images were very well drawn and easy to understand) and they were accompanied with relevant information. The Abnormal Development section was very informative, however it would be better to insert more images in this section as it is quite an important topic.

*Future questions and Glossary were left blank and would be very useful if they were done but I assume that they would be completed with time. Overall, the page seems to have a good amount of information on it so far, well done.

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This wiki page is very informative and a good read! When reading I noticed that the images don’t have a figure number, although this isn’t necessary, it can make it easy to refer to figures in text and therefore explain them better. For the heading lung histology, you can add proper dot points by adding an asterix before the information, this will make your page present better. Both headings future questions and current research need to be finished as they are incomplete. Using self drawn pictures makes your page easy to follow and understand, this is a great feature of your page. Copyright information is added well for the most part, however I found some images under the heading “Developmental signaling processes” which didn’t have any copyright information or an appropriate description, also make sure the student template is added at the end of every image description. I particularly enjoyed the timeline, it is very well written and is easy to understand. Good job on the project thus far.

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A good page going through a lot of the main steps required for the project page, but the page needs a lot of references.

* '''The Lung Anatomy, Histology, and Cardiovasculature''' sections give a good and short understanding of the lungs. The Histology part could need a better layout using the wiki-formatting. All the sections need references! There are almost no references in these sections. I like the big introduction to the lungs, but I am not sure how much it has to do with the embryonic development – especially the Histology part. The self-drawn pictures support the learning when reading, but they are a bit weak in colors. I must click on the figure and then zoom to read and see details of the figures. It would be nice if you can see details at the same time reading the project page. Maybe you should draw the pictures with a more colorful pen.
*'''The developmental timeline''' is really detailed and has a lot of pictures to support the understanding. The images have the right information.
*'''The Conducting System''' section has two pictures that need more information on the picture page – like copyright information. You can look on the image tutorial how do give a picture page proper information or look through some of the other sections on your group project.
*'''Alveolus: the functional unit:''' This section explains a study about overweight in pregnancy, but does not give the reference of the study. It is important to tell the reader where you found this study.
*'''Developmental signaling processes''' section gives a good, short description. Easy to read and understand. But both pictures are missing detailed information – also copyright information. You also mention “a recent study” without giving a reference to the study.
*'''Current understandings and areas of research''' section is missing the context.
*'''Animal Models''' section has a good context and a good setup but could use a brief introduction to what you are going to talk about. Maybe also a figure could be nice to support the reading. You also mention Bmp as a key pathway but does not explain much about it. Since it is mentioned in the short introduction, then the reader would expect that there will be more information about that specific pathway.
*'''Abnormal Development''' is a really good section. It has a lot of references, is easy to read and understand, has the right information on the pictures, beautiful layout. I like that it gives a short understanding of the different abnormalities.

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This page is really impressive when the hand drawn images caught my eye as well as the balanced text-to-images ratio. It is well organised and there was a decent flow throughout the page. It is useful that keywords were formatted to be in bold formatting to draw the attention of the readers to the main terms. The development timeline is very fascinating, it had a description as well as images. Summaries are well-informative as well as brief in some sections. Some images were reference properly and copyright approval was provided. Abnormal development was neatly organised into sections and appropriate journal articles for evidence. However, there are a few abnormalities that did not feature an image to provide more visual aid to the readers.

The 'Alveolus' was left in bold format while the rest were in normal format, this could be easily changed in the edit page. The hand drawn images did not provide a reference where it was based off. Also, one of the images has a very low resolution ("This image is a stylised typical developmental branching pattern over time in a lung bud."). The images should be encased in boxes and a label underneath would be neater. Laboratory results from the animal models would be useful to see. The lung histology section didn't provide any references. The movies section disrupts the flow of the sections, it might be best to place them at the bottom of the page.

This page seems like it is almost complete.

Revise the reference list. Some were left as links and the overall reference formatting was inconsistent. Some were left as APA format and some were left in another format. There was a cite error in one of the references as well.

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Overall, this page has a good arrangement of information. For the lung anatomy, histology and cardiovasculature, the content is concise and good. The images were all self drawn and a lot of effort has been put to it. Good job to the person who did it. However, for the lung anatomy, histology and cardiovasculature, there are no references at all. Also, for the lung histology, perhaps adding in histological images and referencing it when writing the text would make the section better. The developmental timeline was also very well done. I love how all the information was presented in a table and was easy to follow through. The images had their copyright statements, brief overview and proper referencing. Again, there are no references for the structure of respiratory network and its sub sections and for the developmental signalling sections. Also, the images should be labelled as figure 1 or table 1 and could be mentioned in the text where appropriate. Perhaps a glossary could benefit this page. The abnormalities section was well referenced and there was a fair amount of abnormalities covered. Maybe more images could be added.

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This page is very well-structured and demonstrates an extensive understanding of the topic at hand. I found the headings and subheadings easy to follow and contributes to a smooth flow of the page which had a very ‘step-by-step’ feel. References are fairly consistent throughout, however a significant amount of the areas are lacking any acknowledgement to research including the information under the subheading “Animal Models”, “Developmental signaling processes”, etc. Good use of diagrams, especially in depicting the anatomical and histological features of the lung and linking to key points on the timeline – I felt it accompanied the text really well and did not overcomplicate or confuse the concepts. Referring to these images as figures would enhance the quality of the writing overall. Perhaps a section on the functionality of lung structures or an expansion on the function of the layers would provide a good understanding of the topic – I found a lack of focus towards functional aspects overall (only mentioned briefly under “Lung Anatomy”). Entries into the glossary would have helped with understanding the text.

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I don't like that first sentence above Lung Anatomy below the Lung heading. I feel like it is just dumped there so maybe try expanding on this a little bit and making it more into an introduction. The information in the lung anatomy is really good, and that drawing is too! The only suggestion I would make here is instead of saying "this diagram", instead refer to it as Figure 1 and then label the image Figure 1. The lung histology information and picture again was really good, however same thing with reference to the image as I suggested for anatomy. Same thing with cardiovasculature reference to images. The timeline is really great, label your images as figures again though and then can have the little explanation. The brief summary above the timeline could look more structured if you placed it in a simple table.The rest of your information is good, however, some suggestions I would like to make to improve your page would be adding some videos in. These are always engaging and offer a different style of learning for people. A glossary of key terms could also benefit your page. Referencing overall looks good, however, there are a few errors in your referencing. Overall really great page though.

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This project page is very detailed and extensive yet still clear and easy to follow. The tables and many diagrams make the page very engaging. The material is relevant and informative. The structure is well layed out with the use of headigs and subheadings. The use of movies in the ‘current understandings and areas of research’ is very creative and makes the content easier to understand. You have clearly put a lot of time and effort into this project and I only have a few minor recommendations for improvement. Firstly the in-text referencing is minimal in some sections and this should be worked on before the project is due. Also a more detailed and descriptive introduction section could be used to explain what the project is about. Also some of the diagrams I believe are too large and are overwhelming on the page. A large heading of ‘The Lungs’ could also be placed at the top of the page in larger writing to make it more engaging, perhaps with a simple diagram of the lungs.
Overall, congratulations this project is extremely well done.

---

Lung histology and cardiovascular are beautifully drawn but maybe the terms could be bolded because it is a little hard to fully make out the labels on the diagrams. I like that you guys integrated both the information and diagrams together by referring to them in the text instead of just planting the image there without referring to it. It makes the page enjoyable to read. Also, referencing done throughout the abnormalities section is thorough and indicative of the extensive research done on it, good job. For the developmental timeline, it might help to move the pictures below the table--and label the images-- so that the table is only text and more easy to read all in one instead of having the images adding unnecessary spacing. This may be a personal preference however. For developmental signalling processes, both images containing information about FGF10 have the descriptions below them. It might help to add that descriptions to the images themselves so that they don’t interrupt the flow of that section. There is some information missing from current research, future questions, and glossary hat need to be completed as well.

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This peer review is based on the relevant dot points of the ‘Group Assessment Criteria’, as well as subheadings suggested by Mark. This information can be found on the student page.
{| border="1" align="left"
|-
|Criteria
|Strengths
|Weaknesses
|-
| 1. The choice of content shows a good understanding of the topic area
| The developmental timeline is excellent; this section is very detailed and the ideas are expressed clearly. The accompanying images for each stage of development enhance the information in the table and make some of the more complex ideas easier to visualize.

The ‘lung anatomy’ and ‘lung histology’ sections provide background information that makes the rest of the wiki page easier to comprehend. The student-drawn images in these sections are really well done, and make the ideas in the text easier to understand.

The ‘animal models’ and ‘abnormal development’ sections are explained clearly and in detail.
The ‘key discoveries’ component of the assignment was addressed well (I liked how it was integrated with the developmental timeline).
The information in ‘developmental signaling processes’ was expressed clearly, and covered the section in adequate detail. The accompanying images also enhance the information presented in this section.

Overall, the wiki page has an excellent layout, with the chosen sub headings making the page easier to follow.
| The ‘future questions’ and ‘current research’ sections of the wiki page lack content. There are some references to current research throughout the wiki page (see ‘alveolus: the functioning unit), however descriptions of the findings are often vague and there is no information included about the source (e.g. the authors, the date, the title of the research paper).

Some sections of the wiki page may be improved by adding visual aids (e.g. in ‘animal models’)
|--
|2. Content is correctly cited and referenced
|There have been attempts at referencing throughout the assignment. A reference list has been produced and appears mostly correct. The ‘abnormal development’ section was referenced particularly well.

The reference list is extensive, with the majority of the sources being peer-reviewed primary research articles.

Most of the images on the wiki page have been referenced correctly (see all images in ‘developmental timeline’)
|Referencing throughout the wiki page is inconsistent. Many areas lack referencing entirely (see ‘lung anatomy’ and ‘lung histology’), and other sections have minimal in-text citations. Remember to cite any information that is not original (in either wording or idea)

Student drawn images from the ‘lung anatomy’, ‘lung histology’ and ‘lung cardio vasculature’ are not referenced correctly. Remember to cite the source from which the image was derived.

Some references have been repeated in the reference list (see references 15 and 16).
|-
|3. The wiki has an element of teaching at a peer level
|The information on the wiki page is written at a level appropriate for peers. The ‘anatomy of the eye’ section provides background information that clarifies information further down the wiki page.

Most of the included diagrams and tables enhance the written information.
|Many of the acronyms and terms used in this assignment are either poorly explained, or not explained at all. Be sure to add definitions under the ‘glossary’ section so the reader can more easily comprehend some of the more difficult subject areas.

Some images on the page don’t have descriptions. Try adding descriptions to make the images easier to understand.
|-
|4. Relates the topic and content of the Wiki entry to learning aims of embryology
|The wiki page addresses most of the relevant aims of embryology, including embryonic development, abnormal development, signaling processes, animal models and key discoveries.
|The wiki page lacks content relevant to other aims of embryology, such as current research. Be sure to add some information under this sub-heading.
|-
|5. The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic
|Much of the content on the page has been well researched, particularly the developmental timeline.

The extensive reference list shows that, overall, this topic has been well researched across a wide variety of sources.
|No links to other pages on the UNSW embryology wiki have been included. Try linking this wiki page to other aspects of the embryology wiki, such as the ‘lecture 11- respiratory’ page.
|}
--- Strengths: 
• The wiki page appears to explore a variety of topics regarding the development of the lung, ranging from topics such as lung anatomy and histology, developmental origin andt and also abnormalities associated with development. Furthermore, all topics are relevant to lung development (criteria 1). In addition, a variety of images, tables and movies have been utilized alongside the written-text (criteria 2). This helps present information to students who prefer to learn visually. 
• The contents are presented in an appropriate level for the peer. The author for most of the time attempts to provide clarification for acronym accompanied with images and tables that make it easier for the peer learning (criteria 4). 
• The authors of this wiki page have also successfully described evidence of significant research relating to basic and applied sciences that goes beyond the formal teaching activities (criteria 5) by exploring animal models that have contributed to our understanding of lung development. The authors have made an excellent start by describing mouse models with respect to different gene signaling processes and their involvement in lung development.
 
Areas of improvement: 
• Authors should provide a more detailed description of the signaling processes involved in lung development (FGF and SHH)., Also, very few signaling pathways have been listed under this subheading. 
• The author seems to have some citation errors in the reference list (article 22). Some section (lung anatomy, lung histology, the conducting system, alveolus and current research) seem to not have any in-text citation. The articles on hyaline membrane disease seem very old and they could be outdated. 
• Some subheadings are not explained in details (lung cardiovascular) whereas other (current understanding and area of research and future question) lack contents.
• Some acronyms lack clarification such as Sox9 and HS-GAG as the author provide a brief description of their role without attempting to explain what they are. Also, some of the drawn images are not very clear for the reviewer. 
• Authors may have described the history of research which may have contributed to our current understanding of lung development. For example a timeline may be developed to clearly describe this (criteria 6).

Grade: DISTINCTION

General Comment:
This wiki page has addressed most aspects of this assignment really well. Only a few areas need some improvement.

---
'''Peer review project 5'''

* The project contained both developmental origin, timeline, signalling processes, current research and findings, animals model and abnormal development sections. The project therefore has all the sections which were a requirement for the project. But when you read the developmental origin section it does not say which germ layer it comes from. That is written in another section which I find confusing.
* Good idea drawing your own pictures, but because it is done with a pencil it is difficult to see what’s written on the picture.
* I like the anatomy introduction to the lungs – but I don’t see how the histology part is relevant to the project
* The abnormal development section was well-written and seemed like the group had done their research
* The current research section is still empty
* I liked the development timeline with the historical discoveries. But I think the development is the key stone of the project and therefore it would be nice if it had is own section instead of being the table. But the context itself was good
* I think the conducting system section is good and I like how you referred to the signalling processes which is also well described.
* Some sections still need referencing
* I liked that you included videos in your project

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Introduction could be longer, briefly introduce what you are going to discuss in this project page. The drawings are nice but could have been better if they were darker and coloured. In the glossary section, everyone do this as you go with your part as there are lots of technical terms. With those pictures included on the page, give them a name e.g. Figure 1, figure 2 etc. and then state them in the text where you would like the readers to see. As seen in the lung cardiovasculature and lung history section, it starts off with “this diagram”, the diagram should be indicated for example: Figure 1 shows…, or the diagram (figure 1) on the right shows … etc. The lung history and structure of respiratory network section are not referenced. The developmental timeline is well presented with both text and images, well referenced, and constructed nicely in the table. In the current understanding, summaries of journal articles and their findings would be beneficial. With animal models, it needs to be referenced and include a few figures. Image showing each of the abnormality in development is a bonus as well. In the other hand, the texts in the abnormal section are nice written, easy to understand and referenced well which show a lot of researches have put into this.

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The anatomy, histology and cardiovasculature sections are written and structured very well. The figures are direct, clear and enhance the text. The bolded words highlight anatomy specific for the lung and would be wonderful for the future glossary. Timeline is formatted extremely well and the level of detail coupled with the figures used is excellent. The structure of the respiratory network and the development signalling pathways are again done very well but would benefit from deeper referencing. The inclusion of short movies is entertaining and a helpful learning tool. Abnormal development was covered extensively and referenced well. Overall there was a cohesive writing style and approach to the topics, which flowed very well and created an engaging page.

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* Structure of respiratory network
** Should be moved upwards and linked with anatomy
* Animal models
** Section could have used some introductory description to give context on why this section is being explored and its importance
* Overall, solid effort. However:
** Minor grammatical errors present throughout the page
** Some diagrams lacked descriptions and figure legends/abbreviation definitions – diagrams should be self-explanatory and be understandable in combination with their descriptions, when taken out of their contexts within the page
** Use of intext citations can be improved upon
*** Relative lack of citations suggests presence of uncited information in the page
** Remember to remove zIDs before final submission

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Really well done. I think your project is very straight to the point; there is a lot of content, but it doesn't feel overwhelming and I put this down to your formatting, use of diagrams and tables. Very good job on the developmental timeline. Everything is easy to understand, there isn't too much info and your images and references are all appropriate. I particularly like how you've done your signalling section. I think a lot of groups have presented very well researched information on signalling, but that it has been too overwhelming where as you guys have presented a short and sweet summary of your main 4 processes with relevant diagrams. The language in this section was appropriate for peer level, so that made it easy for me to follow rather than having to re-read sentences over and over again because they contained too many complex terms. Well done on finding relevant videos to support your animal models sections, I personally find videos more helpful than diagrams so this definitely was a good addition to your project, and you've provided a nice short summary of what to expect in each video too. Your animal models section has a good amount of detail without being too overwhelming, however you need references there. Well done on your abnormalities section - although there is quite a bit of info, you have provided the main important points which made it easy to follow. Perhaps more pictures could be added to it though.

Overall, it's clear you haven't finished but it does seem like you know what you are doing. Your project has been easy to read with many relevant figures, tables and videos - well done. There is some work to be done on referencing, however, for the most part all the things you need to improve can be easily done. Good job

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*Most references are missing especially in the introduction, structure of respiratory network, developmental signaling processes and animal models. The group may want to decide on one style of referencing for eg. APA or BJP.
*Good inclusion of several images that are relevant and they facilitate understanding. However, the images are not properly captioned and referenced.
*Good and consistent effort could be seen from various sections of the page with clear organization of content in tables and paragraphs. Content is generally fine with good elaboration that is easy to follow.
*The focus of the page is also evenly distributed instead of skewing towards one.

__

GROUP 5

Lung Anatomy/Histology/Cardiovasculature: I think this section is an excellent start to your groups page - the histology section especially adds some depth. The drawings are really nice to view too! Developmental Origins/Timeline: the table is really well structured and there is a nice amount of depth in the description. I like the inclusion of historical developments also Structure/Developmental Signalling: This section flows nicely on from the previous subheadings and is also well written. However there is a lack of referencing in both of these sections Abnormal development: again a good amount of depth and well written.

Overall: not much to fault with this project it looks like you guys are on the right track!

Talk:2017 Group Project 3

2017-10-12T05:27:43Z

Z3416557:

{{ANAT2341Project2017discussion}}



==Suggested Starting Places==
[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 10:15, 14 August 2017 (AEST) OK Group 3 below are some starting places.

{{Heart Links}}

PubMed Searches: [http://www.ncbi.nlm.nih.gov/pubmed?term=Heart+Development ''Heart Development''] | [http://www.ncbi.nlm.nih.gov/pubmed?term=Cardiac+Development ''Cardiac Development'']

BMC Dev Biol Search: [http://www.biomedcentral.com/bmcdevbiol/search/results?terms=Heart+Development ''Heart Development'']

Recent papers

<pubmed limit=5>Heart+Development</pubmed>

==Group Topic Intro==

=Peer Review=

'''Peer review project 3:'''

Some general comments to the project:
*The project contained both developmental origin, timeline, signalling processes, current research and findings, animals model and abnormal development sections. The project therefore has all the sections which were a requirement for the project.
* Overall, I think the project was good. It was well written, easy to understand as a student, the sections correlated well and the context was good. I especially liked the signalling section, even though some context is missing. I think the idea of adding a treatment part to project is a good but I could not find it in the project. As mentioned some context is missing, which is the notch pathway, sonic hedgehog and retinoic acid sections.
* The project has a good introduction. You have a clear idea of what you are about to read, which is nice.
* The layout could be a lot better, I think the picture location could be adjusted. In the developmental origin part, the pictures make the section look very confusing. Some of the subheadings, like the abnormal development is pushed to side by the pictures, so when you scroll down the project you miss it.
* In general, the pictures miss their caption, sources and number. Therefore, you do not know which picture there is referred to when you are reading the project. I miss some more pictures in the developmental sections. Some of the home made drawing is not very descriptive
* In the developmental origin section I think the last sentence is very long. You get so much information in one sentence that you sometimes forget what you just read.
* The timeline is easy to read and understand. Could contain some key discoveries.
* Thought the glossary of terms is a nice addition to the project.
* Overall the referencing is good, but in some sections like primary heart field and heart tube formation, the referencing is missing. In some sections the articles/or links are at the bottom of the section, which makes it a little confusing.
* I don’t feel like the primary heart field and heart tube formation correlates very well with the secondary heart field and cardiac looping section. When I start reading the latter I feel like I am starting on something completely new instead of continuing reading on the heart developing. I get the feeling I am reading two different persons work, and some work should be put into these sections to make it feel more fluent.
* An idea for your project could be that you add a short anatomy section after the introduction, so the reader gets a picture and an overview of how the heart is structured. Then it is easier to understand the developing of the heart when you know how the heart is going to end up looking like.

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Don’t forget to remove the hyperlinks that are under ‘Heart’ at the beginning of the page. Remove student numbers from the page. Add a brief description under images so that readers will understand what the image is showing. Remember to move references that are written in some sections to the ‘References’ subheading. The Notch Pathway is incomplete.

Subheadings and content that have been used show a good understanding of the topic area. The use of a table for the ‘Development Timeline’ shows the teams innovativeness. The use of simple sentences in the table allows readers to understand content simply. References have been done well, they are cited properly. The team have used their own images to show their understanding of the heart. The images that they have used have been properly cited: there are references, copyright statements and the Student Image template. Thorough description of abnormal development, animal models and current research which shows the comprehensive research that was done for the heart. The use of Glossary of Terms is helpful to readers who may not understand what some terms are.

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Very informative and well written wiki. The glossary of terms is particularly useful and presented beautifully. The frequent addition of images and hand-made drawings are really good as they provide a useful visual reference point. The inclusion of a brief overview about the different animals studied in regards to the heart is very interesting. There is a minor spelling error in the table referring to Developmental timeline (week 5). The use of references is great, however maybe just include the links at the bottom of the wiki, to assist with the flow of information. Also add a description of your images so that viewers can more easily identify how the image relates to the text and the relevance of it. Overall, a really good wiki and well done.

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The project is very good. There is a lot information on the page, there is a good description of each picture when you click on them, and there is a good brief introduction of each topic before going into depth on certain points. Most things are described clearly with pictures to support the information. Ending the project with a glossary of terms adds clarity to the project.

In particular, the “Developmental Signalling Processes” section is excellent. There is a description of where molecules are expressed, what cells they act on, the molecules’ roles in the cell signalling pathway on individual cells, and the molecules’ roles in overall heart development. The table describing different types of FGF signalling is excellent. In this section and throughout the project, there is a lot of description of research that has led to the discovery of the information presented on this page. The section “Animal Models” and “Current Research and Findings” add to this.

There are still a couple things to be fixed before the project is complete. There are some grammatical and spelling errors, particularly in “Proepicardium and Coronary Heart Development” that need to be edited. Some subheadings have nothing under them. Some references need to be fixed. Copyright information is needed when you click on some of the pictures. Instead of just using a paragraph style, emphasizing information by bolding specific words or using bulleted information may make the project easier to read and understand. Near the beginning of the project, a picture of the locations of the truncus arteriosus, bulbus cordis, primitive ventricle, and primitive atrium in the heart tube may add to the description of early development. In addition, a description of valve development could add to the project. Overall very good project.

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Use of headings and subheadings break this complex developmental process in to understandable, clear sections.
The images chosen to reinforce the material are appropriate and I particularly like that time has been taken to draw a number of these.
There does seem to be an awful lot of information, and I wonder if this can be cut down at all. For example there is the section on signaling during development, which is a more complex section to understand. This is greatly helped by the diagrams but I can see that there are additional headings that are yet to have information added. It might be an idea to pick a few signaling pathways that occur and really perfect those. I think it has the potential to become very confusing to the reader otherwise.
It is very useful to the reader that you have included a glossary of terms, however I wonder if it may be more effective if this table is placed at the beginning of the page, or as a link at the top that can be opened up, so as the reader can familirise themselves with the terms prior to reading the page.
The page appears to be referenced extensively throughout and appropriately. Good job

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*Overall, this page has a good structure and was enjoyable to read. The headings and subheadings were clear and made it easier to understand the developmental process of the Heart.

*Perhaps it would be better to include relevant background information of the heart (such as blood flow and structure) before delving into the developmental process straightaway.

*There is a good amount of images (and well-drawn images) accompanying the text which aided in understanding the content. However some were not labelled, such as in Developmental Origin where in the text you referred to the images “In figure 2…” and “See figure 4” but the images were not labelled so it was difficult to tell which images you were referring to.

*The table on the Development Timeline was short and concise which was good however it would be better to insert images in the different stages to make it easier to visualise.

*Most parts were cited correctly and properly, however some parts need to be fixed; the Pubmed article reference by “Antoon Moorman” appears in several sections of the page and needs to be deleted. Most sections had a good amount of references, however some sections weren't cited at all such as "Current Research and Findings and "Cardiac Stem Cells".

*Some sections were left blank (The Notch Pathway, Sonic Hedgehog, and Retinoic Acid) which gives the page an unfinished feel, however I assume they will be completed over time. Glossary of terms was clever and made the content easier to understand (the heart is quite complicated to understand). Well done overall.

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Overall, this page had a finished feel because the page is so heavily packed with information, there are some sections that were not completed. There is however, a lot of information that may leave the reader feeling a bit overwhelmed. Some sections are also hard to understand and comprehend especially due to the heavy use of biotechnological jargon (ie. SMAD-dependent, SMAD-independent pathways, β-catenin). A terminology/glossary section would be extremely helpful for this issue. I'd advise using more images in "Abnormal Development" (ie. x-rays or physical observations of sufferers) to help the reader visualise such abnormalities. Referencing under images should be moved to the references section and should be referenced using the '''''< ref >''' '''< / ref >''''' if in text. Overall, there is a lot of information, some of which is not necessarily important. I'd advise to cut down, make paragraphs more simple and straight to the point, and use images to help the reader visually understand and comprehend.

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Introduction is very good and explains a lot. Under the heading “Primary heart field and heart tube formation” – the reference at the bottom should be removed.
Secondary heart field and cardiac looping: First sentence doesn’t really make sense, maybe switch it up a bit.
Under current research and findings you have labelled a figure figure 1, when it is not the first figure in your wiki page, seems a little confusing. Images also don’t have appriopriate copyright info, description and referencing. Also figure 2 is placed right in the middle of the sentence, maybe put it to the right so it doesn’t interrupt reading.
Information could be formatted better under the heading atrial septal defect! Maybe some subheadings for the different defects? Same goes with the ventricular septal defect, its easier to read when things are broken up. Glossary is very good!

All the information written on your page is very well written and easily understood.
Images could be labelled better, add a figure to each of them as when you are referring to figure 1 and 2 in your writing, the images aren’t labelled so its hard to tell what image you are referring to.
With references, I don’t like how there is a bunch at the end of some headings? Could be because you still need to read them but looks messy.
There is an overwhelming amount of information, so good job on doing so much research but it was quite tedious to read, not sure if this much information is needed? But it is very hard to fault your wiki page so this might be a bit picky.

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The introduction is a brief and clear overview of the page. I liked how you acknowledged what your page will explore about the heart development. The “Developmental origin” subheading had good information and good diagrams in addition. However, I would adjust your layout a bit in this section so that the diagrams don’t look so awkward. You could do this by breaking down that second paragraph. The timeline provided a brief overview but I would also suggest adding another column for images. There is also a spelling error on week 5 – it says “srtats” where it should be “starts”.
As you go into “primary heart field and heart tube formation”, “secondary heart field and cardiac looping” and the next few sections, the references appear at the bottom of the sections. You should fix this so that they only appear in the reference list at the end. You could also probably bold “heart tube fusion”, “heart looping” and other terms in your developmental timeline since you explore them in depth.
The “developmental signalling process” subheading is very detailed. Since you also have a few more parts to complete into this section, it might be better to try to minimise some of the text. Your inclusion of current research is good and unique as you explore one paper in depth. However, I would suggest that you find another one or two. The “animal models” subheading should probably have a diagram or two of the referenced research papers if possible. Again with “abnormal development” subheading I would suggest some more images to see what these defects look like and possibly cutting down some text. In “future questions” you might also be able to provide a possible direction research might take to potentially answer this question. Also, you had a very good, long list of references.

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The page goes through everything required for the project page. It would be nice if the pictures on the page have a figure number and a short title on the figures, so it is easier for the reader to understand what figure belongs to what part of the section. A figure number on the picture makes it able for the writer to refer to a specific picture. There is a good use of tables and self-drawn figures/picture. This makes the page clearer and more readable. There are some references on the page that needs a different formatting, so it is not fully viewed in the sections. It is important that the references are given right after the specific section and not at the bottom of the section.

*'''The Introduction''' section gives a good excitement for the reader before reading the page. This gives an idea of what information to expect from the page. A little section about the anatomy of the heart and a picture could give a better preparation for the reader to understand the developmental part of the heart.
*'''The Development Origin''' section has a bit confusing layout.
*I like that the '''Cardiac Neural Crest and Outflow tract''' sections have a self-drawn picture, but maybe you can draw it a bit clearer, so it is easier to read the writing and understand the figure There is no figure text on the page of the figure.
*'''Current Research And Findings, Animal Models and Abnormal Development:''' These sections have a bit of a messy layout. The context is good, but there I a lot of text and pictures kind of mingling into each other. You could make these sections more separate in the layout.
*'''The Glossary of terms''' helps the reader a lot.

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The headings were all neat, concise and impressive. It successfully highlighted and sectioned the key topics in the development of the heart. The addition of the technical signalling pathways and the details of the development were well summarised with appropriate references in superscript format. There was a nice variety of visual resources, both hand drawn and externally sourced. Most images have their copyright approval and reference included perfectly, except "Figure 1 Morphological defects in CTCF mutant embryonic hearts" and "Figure 2 - defects of mitochondria in CTCF mutant hearts". There was a nice flow throughout the page through the use of effective paragraph sectioning. The table for the glossary of terms was really useful and neat.

Some of the images didn't have a box around it and these figures were not labelled, this should be easily changed in the edit mode. Some of the hand drawn images were somewhat unclear, due to the writing as well as the rough outline of the heart. Signatures should also be removed. The references were also retained in the bottom of the sections. It was a confusing because it wasn't next to any paragraphs that needed to be referenced. A reference was also repeated in this section.

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*Introduction
**Introduction is clear with explanation on why the group decided to focus on heart as well as a brief outline of the page.

*Developmental origin
**Good use of images that are relevant in explaining the developmental origin of the heart. References are also made to the figures. However, captions for the images are missing so it is unclear as to which is figure 2 that the author is making reference to.
**Clear explanation that is easy to understand.

*Developmental timeline
**Good use of a table in summarising the embryonic developmental timeline of heart.
**Elaboration for the development of heart during each week is also clear and extensive. A suggestion would be to include the week i.e. “Week 2: primary heart field and heart tube formation” for the subheadings as it can get confusing easily having to scroll back to the table.
**Some references are missing.
**Some images are well labeled but some are not.

*Developmental signaling processes
**Clear explanation that is coupled with images that are relevant to developmental signaling processes.

*Future questions
**The questions listed seem abrupt. Author may want to consider including the significance and need to further investigate these questions.

*Glossary of terms
**Author may want to consider arranging the glossaries in alphabetical order. Otherwise, good inclusion of a list of terms.

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''For example:''
"This image is based upon Robert H Anderson, Sandra Webb, Nigel A Brown, Wouter Lamers, Antoon Moorman Development of the heart: (3) formation of the ventricular outflow tracts, arterial valves, and intrapericardial arterial trunks. Heart: 2003, 89(9);1110-8 PubMed 12923046

Robert H Anderson, Sandra Webb, Nigel A Brown, Wouter Lamers, Antoon Moorman Development of the heart: (3) formation of the ventricular outflow tracts, arterial valves, and intrapericardial arterial trunks. Heart: 2003, 89(9);1110-8 PubMed 12923046

Marc Sylva, Maurice J B van den Hoff, Antoon F M Moorman Development of the human heart. Am. J. Med. Genet. A: 2014, 164A(6);1347-71 PubMed 23633400"

Finally, there is a great variety of reputable sources of information. The only thing that needs changing is that the reference list should be revised. Some were left as a link and the list were inconsistent with its reference format.

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This wikipage had all the sections required for this assignment and the team was very detailed in their content. There was also a good amount of referencing. However for certain areas, the entire reference was there instead of just the number. Also, the student numbers should be removed from the page. There was also a good number of photos used and it was good that they had a mix between self-drawn images and images obtained online. However, a way that could improve the images would be to add a description or a caption under each figure so it's easier to know what the picture is about. Some photos in this article lacked description, reference and copyright information, so that could be added as well. For most of the article, I can see that the team carried out a great amount of research for this topic, however it was a little difficult to understand some parts as they were very lengthy and slightly too content heavy. For the developmental timeline, the use of a table was good but the information could be presented in a more concise manner and the headings could be slightly more prominent to make it more readable. The signalling processes was also very well researched but quite lengthy, perhaps a few main signalling pathways could be chosen instead. For the abnormal developments, each abnormalities were well researched on. Perhaps images could be added to show the abnormalities and also maybe one or two more defects would be good. Overall, I think this group did a great job in researching and providing information on this wikipage. Maybe with a bit of tweaking here and there to make it more concise and readable, this wikipage would make a really good project.

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Well-structured page which seems to be quite detailed and long to read. The extensive use of subheadings make it a little harder to follow in some areas such as under “Developmental timeline”, where after the table the subheading “Primary Heart Field and…” appears to be a little misplaced or is lacking flow completely. Need to remove the student numbers from the page and also the two links under the initial “Heart” heading. In text referencing throughout the page seems to be consistent for the most part however, there are some areas where the correct format needs to be used (i.e., under “Wnt signaling” and “Cardiac Neural Crest and Outflow tract”). Some images do have a description of what is addressed however, many of them do not – this expansion would help with the overall reading experience as well as add further information for understanding. Overall, an extensive knowledge of the topic is well demonstrated through an attention to detail – but perhaps a more concise approach would add some clarity to the text.

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The introduction was very good! I like how it introduced why the heart is so critical in early development, explained what you were going to discuss and where there would be gaps due to a lack of medical knowledge. The information in developmental origin and the developmental timeline is really great, however, I think you need to consider joining these two headings and not splitting them into one. You also state in developmental origin "as seen in figure two", however, none of your images have figure titles so I am not sure which figure you're actually referring to. The timeline is a good basic reference point, so I think it would be nice for it to be before the origin outline as it gives the basics which you then go into more detail about. I like that you put in the developmental signalling processes and then outlined each one of these, obviously the rest of those processes that have subheadings but no information just need to be finished. The current research is really interesting, again images just need a figure of some sort. The future questions section is a little confusing as I'm not sure if that's an area you're going to go into more depth over or if that's a future question you think research should look in to? So a clarification would be good. The glossary of terms is super helpful and all referencing looks good!

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At first glance this project seems very detailed and lengthy. In my opinion, it could have too much text and maybe summarizing and condensing some sections could be beneficial. Collapsible windows or maybe more use of subheadings or dot points could be used to make the page clearer and less overwhelming. The diagrams and tables are very engaging and informative. However I do think the position and sizing of the diagrams could be improved to align it with the text better. The text and most of the diagrams seem to be well referenced. Another suggestion for this page would be to make the overall title of ‘Heart’ larger and clearer, perhaps include a diagram of the heart with the title to make it more attractive. The overall title should also be placed above the contents section.
Despite these suggestions, well done this page is very detailed and informative and you have clearly put a lot of work and effort into it.

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Great detailing of the development and signaling processes involved, it really showed me that the group had extensive knowledge on this topic. In addition, there is a good balance of personal images (e.g. wnt signaling diagram) and web images which showed me that the group dedicated time to make sure the reader fully understood each aspect of the topic. Most images also are properly cited with copyright statements, references, and description (some are missing, but overall are done well). It was very helpful to include a glossary of terms at the end for the reader to refer to. An image for the cardiac looping steps would help to visualize steps. Information needs to be added for the notch pathway, sonic hedgehog, retinoic acid. While the detail is very informative, there is a lot of information and can be a little overwhelming. It might help to add more bullet points (with only essential information) or to edit some of the superfluous information. In addition, captions for the images would help so that the reader knows which image you’re referring to when referring to them in the text.

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'Introduction' is clear and informative, well referenced and gives a good outline for the rest of the page. 'Developmental Origin' has a bit of a confusing set up.. pictures are seemingly scattered and need captions. The 'Morphology of the Heart tube formation' hand-drawn figure is almost an exact replica of the original.. not sure if this is allowed because they are so similar. 'Developmental Timeline' has a very brief table.. would benefit from a better description of each week of development. This section has a couple of random references that should be at the bottom. 'Developmental Signalling Processes' diagrams need captions. There is a lot of information here which is very detailed. 'Current Research and Findings' has good subheadings and picture use; pictures need to have copyright information and citations added. Very detailed with good references throughought. 'Future Questions' needs to be added to but has shown evidence of initial research into this area. 'Glossary of terms' is a very good idea that has not yet been shown in other group topics. Maybe look into researching how to link certain words in the article to redirect to the bottom of the page to the Glossary of terms for quick definitions? Some references also need to be properly cited in the 'References' section. Over all, really well researched with some sections needing a bit more work.

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Overall a very in-depth page with most of the required subjects covered. Some general notes; the figures would have benefited from appropriate captions but were helpful nonetheless. Referencing and overall visual formatting could be improved. The page is written well and enjoyable to read.

"Primary heart field and heart tube formation" could benefit from a diagram or figure since it is a lot of text that could be hard to conceptualise. The signalling processes are explained very well and in deep detail. Just a note though; the addressing of so many different variables in the signalling is a little confusing and hard to follow. Perhaps a more condensed response might be a little more straightforward. The diagram of the signalling pathways under "Wnt Signalling" was likewise hard to follow, and no key was given. Current Research and Animal Models were covered well and the explanation for their research and the key results highlighted were fascinating. Abnormal development was likewise addressed very well and the glossary of terms was very much appreciated.

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- Introduction was very well written and great spelling and grammar. Good referencing, simple way to start a page

- Developmental origin of the heart was explained well and I liked how they referenced to the figure in the text as well, showing that the picture is actually important in this section. Correct referencing was used in this section which is good. A moving video of developmental origin of the heart would have been really useful here

- Developmental timeline was a bit too brief, and would help to put some pictures to explain how some of the main steps looked like

- Further explanation of the development was separated and structured well and had good amount of information for each main step. Citation of the reference shouldn’t be here but in the references

- A nice picture was used to explain the difference between straight, looped and converged which I personally found very interesting and informative

- The drawings included were very well drawn, precise and different colours helped differentiate each part of the heart and also referenced.

- I really liked the developmental signalling processes and they had explained each important factor of the process in a lot of detail. Would have been good if they had finished this section. A good use of table to differentiate different FGF and their functions

- Current research and findings selected were definitely very new and also explained in a lot of depth

- Abnormalities section was slightly lacking, although there is good information, adding 3 or 4 more abnormalities would be even better. Some pictures in this section would have made it more interesting and explain the content better.

- Overall, a very nicely set out page with good information in each section and appropriate referencing in most parts. Inclusion of glossary and a large variety of subheadings made this page great. Some further work in some subheadings would make this page perfect.
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- I think your intro was really good because it was very straight to the point and gave a great summary of your project as a whole.
- Developmental origins was well done, not too complex. The diagrams definitely helped break down this complex model. I have seen some helpful videos online that summarise this process, so maybe you could add a video to it? Just because it is still a lot to grasp and if the person is anything like me, they'll find videos more helpful than the diagrams (but your choice of pictures were great and good referencing). The placement of the pictures looks a bit wonky, but I don't think it's something you have control of.
- Developmental timeline table was a bit brief, I think more detail needs to be added to it because the rest of the developmental section has a lot of content; the table should summarise it all so someone can have a quick idea of it all rather than having to read the whole section which is quite lengthy. Good job for having a table in the first place though. The diagrams in this section were relevant and well sized. Once again, a video would be nice but that's just me. Some referencing errors, but that can be easily fixed.
- Great work on the signalling section, it's really complex so I'm sure that would have been a mission to collate however I think it could be less wordy just because it is so hard to follow at times. You've done a lot of research which is great, but maybe shortening it a bit would be more beneficial to readers. Again, videos could help. Good use of the table to summarise it all. I can see that it's not finished, but it seems like you guys know where to go with it. Good referencing.
- I think your abnormal development section was well done, it wasn't too overwhelming and it is very detailed with proper referencing and suitable pictures.
- The stem cells section seemed a bit random to me because it wasn't mentioned in the intro. If it falls under "the possible treatments to be developed in the future", perhaps you could address that in the first sentence because right now it just seems like hey here's some info on stem cells... and I'm here wondering what the relevance of this is. Seems well researched though, just need to state its relevance.
- Future questions a bit empty.
- Glossary is great, maybe you could have a glossary for the signalling part too

Overall it is clear that you guys have put in a lot of time and effort, so well done on that. At times though, it just feels a bit overwhelming. There's good use of diagrams an tables, but I think the amount of content still needs to be a bit more concise. Your referencing for the most part is really good, however some parts in the development section are different, but it's nothing that can't be easily fixed. Overall, good job!

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* Introduction
** Justification of chosen topic was an interesting approach
* Developmental signalling processes
** Links between explored processes and heart development were made by could be more explicitly presented
* Current research and findings
** May have been too extensive at times
*** Felt like there was un-needed focus on methods used in the explored projects. Section could be streamlined to have less focus on methods and more highlighting of results of experiments presented
* Overall, well-structured and well written. However:
** Minor grammatical errors present throughout the page
** Some diagrams lacked descriptions and figure legends/abbreviation definitions – diagrams should be self-explanatory and be understandable in combination with their descriptions, when taken out of their contexts within the page
** Remember to remove zIDs before final submission

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GROUP 3

Introduction: Well written and concise - sets up a good expectation of whats to come Developmental Origin: I like how you have referenced the images in the text - though I would try to fix the image placement (it's hard - I am struggling also!) Developmental Timeline: This section is excellent - great amount of detail, well written, and great supporting images Developmental Signalling Processes: Also a very good section (just keep writing how you have for the rest of the subheadings!) - also need to fix up the referencing of that 2nd image Current Research And Findings: There is a commendable effort here to summarize current research. I might be nitpicking here but maybe try to make this section a little more concise as it is large blocks of text Glossary of Terms: Useful section to include

Overall: The level of research and depth of writing of this page is excellent. There isn't too much to change - and if the rest of the subheadings left to complete are in the same style as the rest of the page I think you guys should be pretty happy!

Talk:2017 Group Project 2

2017-10-12T05:27:08Z

Z3416557:

{{ANAT2341Project2017discussion}}



[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 10:15, 14 August 2017 (AEST) OK Group 2 below are some starting places.

{{Renal Links}}

PubMed Searches: [http://www.ncbi.nlm.nih.gov/pubmed?term=Renal+Development ''Renal Development''] | [http://www.ncbi.nlm.nih.gov/pubmed?term=Kidney+Development ''Kidney Development'']

BMC Dev Biol Search: [http://www.biomedcentral.com/bmcdevbiol/search/results?terms=Renal+Development ''Renal Development'']

Recent papers

<pubmed limit=5>Renal+Development</pubmed>

Yay.

[[User:Z5178275|Z5178275]] ([[User talk:Z5178275|talk]]) 16:48, 10 August 2017 (AEST) I'm keen to do anything, but I think the brain is a little to complex for me. It also seems like a lot of other groups want to do that as well.

Cynthia here, I don't want to do the brain lol. I don't mind anything else though

[[User:Z5076039|Z5076039]] ([[User talk:Z5076039|talk]]) 17:03, 10 August 2017 (AEST)

==Peer Reviews==
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A really well-written and well presented wiki. The information was simplified and therefore was easy to comprehend. The use of images throughout the wiki was highly useful as they provided a visual reference point and enhanced the information presented.

A few things to work on include, take out the links that have been scattered through some of the paragraphs, either reference them with a number (footnote style) or include them in the list at the end. Simplify the section on kidney Blood supply. In the Abnormalities section of the wiki, there is a list of some of the main congenital defects that occur in kidneys, however not all of these dot-points are expanded on. Maybe you could include some more abnormalities that relate to the list or specifically mention that only a selected few are going to be expanded on. The current research section may need some more attention. Overall, the layout is fantastic and well done on a great wiki.

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This page is very informative and easy to read. I like the way it begins with the anatomy of the kidney in the developed human, and then progresses through its embryological development. The inclusion of developmental timeline table aids the flow of the page. Images are well integrated into the page with informative descriptions, however are not correctly referenced and do include the suitable Copyright statement or Student Image Template.

The 'stages of nephron development' subheading includes numbered bullet points, but would appear more finished by using the Wiki bullet points. In the "Genes expressed" section it would be beneficial if the terms RET and GDNF were expanded on. The 'Blood Supply' section is clearly unfinished, but will require in text citations and images would help it to read easier.
The page references well, but many sections are still unfinished. The page would benefit from a glossary at the end, and the "General info on the renal system" section should be included higher up on the page, or integrated into one of the other sections such as under the "Kidney" heading. This page is very easy to read, but still needs some work.
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References should be cited correctly, i.e. don’t leave the links in the paragraphs and use proper citation. The images used should include references, copyright statements as well as the Student Image template required. If there are copyright images the team could be innovative and use their own diagrams to display structures. Use references for the ‘Timeline of Kidney Embryology’ to show that a variety of sources were used to complete the table. Current Research and Future Questions subheading is incomplete. Glossary of terms could be used to explain certain words, for example explaining in simple terms what GDNF and RET are.

Subheadings and content that have been used show a good understanding of the topic area. The team has bolded important words in relation to the kidney structure. The team has also placed a description under the images which allows readers to understand what the image is showing. The use of a table of ‘Timeline of Kidney’ allows readers to understand the content of the wikipage easily (maybe add images to the table). The team has shown comprehensive research; however, they need to show more referencing of sources to display the research that they have done.

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Overall this seems like a very well put together project and is very informative and easy to follow, and enjoyable to read. There is an appropriate balance of both text and visual diagrams, which greatly helped my understanding of the development of the kidneys. Figure 4 appears to be missing a reference. I do think perhaps an animation to explain nephron development may add additional clarity, and would provide another level of interaction for the reader. Perhaps also think about adding a student drawn diagram. The table is a great way to display the developmental stages in an easy to read manner.
The ‘blood supply’ section appears to be copy and paste which I assume will be rewritten? The section on current research is simply a list of PubMed links, and should be expanded to display content that is informative to the reader. Likewise, ‘questions for the future’ and ‘general info on the renal system’ remain as headings without any accompanying information. I think the questions for the future could be an interesting section, however general info I would think will have been covered elsewhere in the project.
The topic has clearly been researched well, and is well referenced, with most references being from scientific papers.
All in all I think this is a high quality project, that will only require a few additional tweaks to take it to the next level.
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There is a lot of good information on this page and it is easy to read and understand. The table that introduces the developmental timetable of kidney development is a quick, clear way to introduce the topic. Bolding the anatomical structures is a good way to emphasize the key information of the kidney anatomy.

The information on the page is represented relatively clearly, but a couple of fixes could add clarity. In the description of the Mesonephric stage, the embryological feature, the nephrogenic chord is first introduced as the nephrogenic chord, then referred to as the nephrogenic duct in the next paragraph. Using the same words to describe the same feature makes it less confusing for the reader. Adding a picture to the “Blood Supply” section would also help visualize the kidney vasculature. There is some information about signalling factors in “Nephron Development” that seems oddly placed and may function better in the “Genes Expressed” section. In “Genes Expressed” there is an introduction of two genes, RET and GDNF. RET is clearly the focus of the section but more information about GDNF would benefit this section. Also, making clear what type of molecules RET and GDNF are (receptors, ligands, transcription factors, etc.) and explaining the mechanism of their interaction would make this section clearer.

There are a couple of subheadings at the end of the project that need information in them, pictures that need copyright information and summary when you click on them, in-text citations that need to be added, and basic spelling and grammatical mistakes, all of which can be fixed with some simple editing. The information is solid, the abnormalities section is very good, and the discussion of current research “Can kidney disease be associated with nephron number?” is a good way to end the project. Overall good project.

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The page flows very well and is easy to read. However, there is incorrect citing or no citing at all for images and texts which can trigger copyright issues, in some sections (mostly the beginning) of the page. The structure and anatomical position is extremely easy to read and comprehend, as well as the use of a table for development. Id advise to insert more images for development and the remaining sections to help the reader visualise the process instead of being overwhelmed by the information. Developmental abnormalities seem to contain information not necessarily needed. Maybe add the 5 paragraphs above "Kidney developmental abnormalities are diverse and they correspond to defects at different stages of kidney development" statement in a separate research topic. Good use of images for abnormalities though. Overall, the page is quite informative and has been researched effectively. It could be improved by slight tweaks in format aforementioned and correct referencing.

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Structure and use of headings is clear and very easy to follow with a good flow. There is good implementation of labelled diagrams all throughout in sections where they are needed which is not only visually appealing, but also well balanced in regards to the amount of text included. References are not included with most of the images; also, whereas some areas are well referenced with in-text citations, other sections lack any form of references. The information is easy to read and understand due to its conciseness and use of numbering as well as shortened paragraphs. However, the initial introduction lacks a cohesive essence as the second sentence on the placenta seems out of place and unrelated to the first sentence. Also in the introduction, the references need to be entered in appropriately as the links aren’t in the form of in text references. Good use of questions as subheadings under “Current Research” as it provides an overview of the topic and peaks the curiosity of the reader – also adding to the enjoyment and ease of reading the research. Overall, well-structured page which is easy to read and is well-organised.

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I found the introduction to the kidney didn't flow very nicely and each sentence and paragraph were just points added in. Also, the grammar and punctuation in the introduction paragraph needs to be edited. The final thing that needs to be altered in the introduction paragraph is the links that have just been placed in. I'm not sure if they are the references but if so they need to be referenced correctly. The anatomical position and kidney structure are written really well! The only improvement I could make is with figure one and two reference them within the writing e.g. "Their inner structure can be divided into 2 main areas: the outer cortex, and the inner medulla, as illustrated in Figure 2", otherwise this section is really great. The timeline of the kidney embryology is good - basic outline which makes it easy to follow such a complex process. To make the page flow in a more succinct manner I think it would be good to put the kidney timeline under the kidney development heading instead of separating the two as the kidney development information expands on the timeline really well. The kidney development information is really good, and I think the images really complete it. However, the link at the end of nephrogenesis needs to be referenced correctly with intext. Also under blood supply, it says "THIS IS COPY AND PASTE" so I'm not sure if that's copied off another page or your own notes but that needs to be fixed. The abnormality section was really good and current research is a really interesting thing to include, that section just needs some more information which I'm sure you guys are already on top of! Overall its a really great page, good effort.

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I believe the headings chosen cover a sufficient amount of points you need in order to describe kidney development!
Referencing needs to be changed, its easy to use the code on the wiki cheat sheet and that automatically makes a reference for you!
When describing position, explain what retroperitoneal means, its not commonly known and also Thoracic 12 (T12) so people know what T12 refers too.
For images, you need to find the copyright information and reference them properly, Mark has step by step instructions on what needs to be included in the image description. There aren’t many references in the first section of the page, it would benefit if you included some. Under nephrogenesis, point 3, you can find the articles pubmed ID and add the reference in that way instead of manually doing it.
For developmental abnormalities, I feel like this could be explained better, it gets technical straight away and this can become quite confusing.
Current research and questions need to be worked on but I’m sure that’s whats intended.
Overall I think the content on this page is very relevant to kidney development and it was interesting to read. The two major things you should fix are image copyright and references and intext referencing.

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The introduction was a clear overview of the kidney, its main parts and its role. The connection to embryological development is great because it ties in with the rest of the page. The only note here is that the references need to be properly referenced, not just pasted with the link. The anatomical position and kidney structure parts were good because there wasn’t too much text and it only served to complement the diagrams. This is a good section to put before kidney embryology as we can understand what is developing as the embryo grows.
The timeline of kidney embryology was very brief. This is not bad considering you go into kidney development in more detail in the next section. However, I think another column for images would be worthwhile for the reader to visualise each stage or week of development.
Again, there are a few referencing errors that I’m sure you’ll rectify soon. There is a good use of references in nephron development. You’ve also clearly noted the copy and paste of the blood supply section. For this part, I would strongly recommend some diagrams because vasculature can be quite complicated to understand with just text.
The subheading, “Developmental abnormalities”, had a good chunk of research at the beginning that gave an overview of types of abnormalities before exploring three in detail. There was also a good amount of referencing. Clearly, the current research subheading is underdeveloped but there seems to be many articles that you will explore.
The reference list will be more reflective of your research once you fix some of those referencing errors.

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Good project page that goes through almost everything required for the page – the Current Research and Future questions section is lacking context though. The project is well written and easy to understand. Some sections have a better layout than others, so maybe you can work on making the same layout for the whole page. Some sections also have the wrong formatting of references, but other sections have perfect formatting. You must be careful with copy-pasting (Blood supply section) text into your project page without giving a reference from where you copy pasted the text from. Some of the pictures on the page also need more information on the image page itself like copyright information. It is good that you have added figure number to your pictures and a little description of it – this helps the reader to understand the context.

*'''The introduction''' to the Kidney is a really good, informative section. You need to change the format of your references in this section though. The layout might be a little bit confusing since there is a title “Kidney Structure” is in the middle of the page due to the pictures on each site.
*'''Nephron development and The developmental Abnormalities:''' These sections have a different layout compared to the earlier sections. It’s a lot of text, so try to make it look a bit more comfortable for the reader to go through. Maybe you can try to make the layout similar to some of the other sections and give the page a better flow.

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This page presents nicely and very easy to read. In the introduction section, instead of pasting those references, put them in pubmed reference properly so they can be put automatically into the references. They have introduced good and enough information on the anatomy of the kidney. It was not fully referenced in the kidney development section but it was well written in this section with informative pictures and figures. It could be easier to direct the text to its picture accordingly. The timeline would be more beneficial if pictures were included. Nice and shot subheadings. In the abnormalities section, brief paragraphs with well-referenced starting off nicely. Pictures and texts are presented fairly good and are easy to see without a mess, but some of the terms were hard to understand e.g."when the left and right kidneys fuse at their lower poles by a '''parenchymal isthmus''' located ventral to the abdominal aorta, forming a "U" shape", maybe have a glossary section at the end of the page. A lot of references in this section is a bonus indicating it was researched well. In the current research section, majority is a list of article links which I assume they are not yet touched on at this state, which is ok. But make sure to have 2-3 journal articles in this section. A few of future question along the way if you have any would be great. Overall, it is a nice written page, looking forward to see this as a whole!

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This wikipage is easy to read and the details provided was informative. The amount of text in each section was just nice and wasnt too overwhelming or insufficient, which was good. Overall, I noticed that the references could be improved. Instead of adding the link at the bottom, the team should use the code to reference such as in the section "Nephron development". Although the use of photos were really helpful and the choice of photos were great in the context they were added in, they were generally inconsistent in either description, reference or copyright information, which should be added to all photos. The anatomical position and kidney structure had clear and concise information and was easily understandable. The timeline of kidney embryology was really nice and I like how it was all 1-2 sentences long, making it really readable. In the section of developmental abnormalities, there is a large amount of text in the beginning that doesnt belong to any abnormality. Perhaps a subheading "Congenital Abnormalities of the Kidney and Urinary Tract" could be added to make it clearer as to what the text is about. Good use of image in each abnormalities though. The article appears to be unfinished but I'm assuming the team will be completing it after this peer review. To sum up, I like the readability of this wikipage and the images chosen, however, referencing and image descriptions could be further looked at for an even better page!

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Overall, this project page is easy to read. Most of the information provided is very concise and specific. For the anatomical position and kidney structure, do remember to add in the references in the text. Before using the short form, do include the full name. For example Thoracic 12 (T12) instead of T12. I really appreciate the timeline of development table as it provides a brief overview before moving onto the details. The section of kidney development is well done with good subheadings to help with the flow of the content. However, more images or videos can be included for better understanding. Again, for the “nephrogenesis” and “ascension” and “genes expressed” section, its lacking references. For the developmental abnormalities, maybe a subheading could be used to categorise the first few paragraphs of information as it was hard to understand the flow of the content. Since it was mentioned that “there are defects in different stages of kidney development”, the team could use this as a basis in arranging the information. Perhaps, the team could assign one abnormality for each stage of the kidney development. I think that would help the section have a better flow. The team have also stated that the information for blood supply and current research is still ongoing. For the images, some images are lacking referencing, the copyright statement and also a brief description explaining the image. This team has kept their page simple and easy to understand. With a few more added information and slight tweaks, It would be a really good page.

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This page is really impressive for its organisation and balanced ratio of texts to images. There is a nice structure and flow in each different sections, this caught my attention and I read through most of the sections without any problems. All of the images were also labelled appropriately, the key words were formatted in bold and certain definitions were stated. These all helped in keeping the page really interesting and organised. A list of abnormalities and its causes were also stated in a very neat and informative matter with bullet points and images. It was nice to see that the research question was relevant and thought provoking.

Some paragraphs were not referenced especially the first paragraphs in each section. In-text citations should be changed into superscripts in some sections. This page contained really visually appealing images however, some images were not referenced and/or it didn't state the copyright message that states it can be reused with no issues. Some of the headings (e.g. 'Stages in nephron formation' and 'Common congenital kidney defects') were in an italics format, this could be changed into another sub-sub heading or maybe increase its font size. Blood supply section should be reviewed, summarised and referenced appropriately.

Information about the kidney development were mostly sourced from reputable journals articles that was published quite recently. However, the reference list section should be reviewed to keep the referencing format consistent. At the moment, it has APA format and some have different format I am not familiar with.

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The layout of this webpage is extremely clear and engaging. The use of diagrams and tables makes the page more appealing to read. I like how the diagrams are split between the left and right sides of the page, the symmetry makes the project aesthetically pleasing. I also think the use of headings and subheadings makes the page well structured and easy to follow.
All the material seems to be relevant and informative. The information and diagrams seem to be well referenced. I think that some paragraphs such as bloody supply and developmental abnormalities need to be broken up as the one large paragraph of text is not appealing to read, however this is understandable as the project is not completed yet. Incorporating diagrams, YouTube videos or perhaps collapsible windows in these sections could be beneficial. Another suggestion for this page would be to make the overall title of ‘Kidney’ larger and clearer, perhaps include a diagram of the kidney with the title to make it more attractive.

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Organization of the page is done really well, especially for Nephrogenesis and the different stages involved. There is a lot of good detail in each section, specifically the abnormalities section (it may help to break down the introduction of the abnormalities with an image however). The subheadings included show a good knowledge of the topic and guide the reader through kidney development. Good support of ideas using helpful images and timeline table of kidney development. I think the page would be more complete if the current research, questions for the future, and general info on the renal system were complete. Also, it may make more sense to put general information at the beginning to orient the reader (depending on what the “general info” entails). Some animal models and examples of signals involved in the “Genes Expressed” section would also help complete the page. For the images, there should be copyright information added, a description of the image, and the proper reference.

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The introduction is clear and well-thought-out; simple enough that the layman can understand but comprehensive enough to lead logically into the more extensive information on the page. Perhaps a discussion of the kidney's function ought to be included with the description of kidney structure. Kidney development; the choice of that particular style of formatting runs a risk of not tying the development with the timeline but the small table at the top serves well to stop that, even if it is a little of a hassle moving back and forth to keep up. The content was well-written and appropriate in voice and depth of knowledge. Visually well-presented with figures appropriately explained. Developmental abnormalities were covered well, and although bullet points may not be the best way to present the information, it allowed for the key points to be understood very quickly and effectively. The transition from topic to topic was logical and flowed appropriately. Some aspects of the page must of course be filled out but overall a well-rounded, well-structured and informative page.

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This peer review is based on the relevant dot points of the ‘Group Assessment Criteria’, as well as subheadings suggested by Mark. This information can be found on the student page.

{| border="1" align="left"
|-
|Criteria
|Strengths
|Weaknesses
|-
| 1. The choice of content shows a good understanding of the topic area
| The embryology timeline is well written and very informative. It gives the reader a general understanding of the process of kidney development before each stage of development is covered in detail.

The topic of ‘kidney development’ is described clearly and in detail. The well-structured subheadings make this section of the wiki page easier to follow. The chosen figures also enhance the information presented, and facilitate the readers understanding.

The brief introduction to the anatomy of the kidney provides a nice introduction to the topic, and helps the reader understand the basics.
| The wiki page is missing several important areas of information:
*There is no section covering key historical discoveries relevant development of the kidneys.
*There is no section on animal models that have been used to advance scientific understanding of kidney development
*The page lacks a glossary of terms

Even though some information regarding signalling processes has been integrated into the 'kidney development’ section, the wiki page may benefit from a section entirely dedicated to signalling processes (this is one of Mark’s recommended sub-headings)

There is currently very little information regarding current research on the wiki page – this section needs some work.

Although the heading “future questions” has been added to the wiki page, there is no information associated with it.
|-
|2. Content is correctly cited and referenced
|There have been attempts at referencing throughout the assignment. A reference list has been produced and appears mostly correct. References have not been repeated throughout the list.

The reference list is comprised mainly of peer-reviewed primary research articles.

Some images have been referenced correctly – see ‘figure 3’.
|Overall, referencing throughout the wiki page is poor. Some sections completely lack referencing (see ‘kidney structure’, ‘genes expressed’). Other sections have only 1 link attached to them (see ‘nephrogenesis’). Any information that is not original (in idea or structure) needs proper sentence-by-sentence citations. The most well-referenced section is the introduction to ‘developmental abnormalities’, and that still contains some uncited material.

Try not to rely on only one source of information per section (see ‘nephrogenesis’). Try to find a variety of research articles to source your material from. This will increase the quality and reliability of the information in the wiki page.

Many of the images have been cited incorrectly and used without permission (see ‘figure 1’ and ‘figure 2’) Remember to include the full reference, the original summary and the copyright license information for each image.
|-
| 3. The wiki has an element of teaching at a peer level
|The information presented is mostly at a level appropriate for peers. Some background information has been provided to aid in the reader’s understanding.
The chosen visual aids make some of the more complex ideas easier to comprehend (see ‘figure 3’). Some of the images also contain helpful descriptions that aid in understanding of the material (see ‘figure 3’ and ‘figure 8’)
|Many of the acronyms and terms used in this assignment are either poorly explained, or not explained at all. By including a glossary, the reader will be able to understand some of the more difficult subject areas.

No student-drawn diagrams have been included in the wiki page. Try to include some hand-drawn images, as well as other devices (e.g. tables, analogies) to aid the reader.
|-
|4. Relates the topic and content of the Wiki entry to learning aims of embryology
|The ‘Kidney development’ section was well-structured and was covered in great detail.

Developmental signaling processes were addressed, which is another important learning aim of embryology.

Current research regarding kidney development has been mentioned.
|There has been no discussion of key discoveries regarding kidney development.

Although a thorough understanding of certain topics areas has been demonstrated, certain areas (such as current research) still need improvement.
|-
|5. The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic
|Certain aspects have been well researched such as anatomy of the kidney, kidney development and developmental abnormalities.
|No links to other pages on the UNSW embryology wiki have been included. Try linking this wiki page to other aspects of the embryology wiki.

The small number of sources cited in the reference list demonstrates a poor and narrow approach to researching this topic. A greater library of sources should be used to develop this page (mainly primary research articles).
|}
---
Strengths: 
• The wiki page appears to explore a variety of topics regarding the development of the kidney, ranging from topics such as nephrogenesis, ascension of the kidneys, the importance of gene expression in kidney development and also abnormalities associated with development. Furthermore, all topics are relevant to kidney development (criteria 1). In addition a variety of images and tables have been utilized alongside the written-text (criteria 2). This helps present information to students who prefer to learn visually. 
• Within the wiki page, a broad variety of references have been included, all of which appear to be recent. All sources included appear to be correctly cited and referenced in-text, thus the authors of the page have clearly satisfied criteria 3. 
• It was also great how the authors have not only discussed abnormalities associated with development, but have also investigated current research being conducted into this particular area of embryonic development. Thus, the authors are on track to fulfilling criteria 5 of the assessment. A possible area to investigate may be to examine whether certain abnormalities may be treated through the application of stem cell therapy for example. 
Areas of improvement: 
• The authors may wish to include videos which may help reinforce information presented within the wiki page. Videos may revolve around the stages of development of the kidney and may appeal to peers who prefer a learning style focused on visual explanation of concepts (criteria 4). 
• The authors may also explore research previously conducted into this field which has allowed our understanding of renal development to grow. Thus authors may include a timeline showing discoveries over the years which have contributed to our understanding. 
• The topic labelled “blood supply” should also include images to perhaps show the vascular map of arteries and veins which branch out towards the kidney. 
• Authors may also wish to create a subheading titled “signaling” in order to describe the signaling processes involved in renal development. Another key improvement would be for the authors to provide a more detailed description of the genes involved in renal development, very few genes have been listed under this subheading.

Grade: CREDIT

General Comment:
Most of the sections on the page have been done well, but some areas still need improvement.

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This page had a good general introduction to the kidneys and their function; the referencing needs to be fixed though. The pictures are helpful but do not have any copyright information or journal referencing which needs to be fixed ASAP. 'Timeline of Kidney Embryology' was very brief. 'Kidney Development' covered it in much more detail. Pictures used were well captioned and useful. Figure 4 in this section needs copyright information and proper citation. Figure 5 needs copyright information. 'Blood Supply' subheading has a 'THIS IS COPY AND PASTE' statement as the paragraph has been copied from a journal article but no reference has been made to said journal article.. I think this needs to be removed ASAP. 'Developmental abnormalities' is well written, referenced and has some bolded words which make it easier to interpret. Subheadings are clear and the pictures are informative. 'Current Research' has not yet been completed but several research articles are shown which is promising. 'Questions for the future' and 'General info on renal system' subheadings also need to be added to. Overall, good start but would benefit from more content. Also each group page needs to have at least one hand-drawn diagram so this should be added.
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- Introduction covered anatomical position and structure which was done well and good use of pictures for kidney structure especially. Incorrect use of referencing in this section (don’t copy and paste the URL in the text and place it in the references)

- Short brief timeline that helped gave quick summary of the development of kidney was done well. Putting pictures or videos of this process would help a lot

- Out of all subheadings, development was done the best and had a lot of info and some limited proper use of referencing

- Including ascensions and genes expressed was good in development and I thought they covered development in a lot of detail. However, one of the subheadings on blood supply was incomplete and was taken straight off from an article. It did mention that this was copied and pasted, but some effort to reword it would be nice to see

- A very detailed explanation of the overview of developmental abnormalities but not many examples of the abnormalities were explained. Including at least 5 more abnormalities would be good to see

- Overall, what was written was good information but more work and detail is needed and probably more subheadings as well. Referencing was poor throughout the page and should be updated as soon as possible

- The references used were from big and trustworthy journals which is good. Glossary included would have been useful

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* Introduction
** Solid with nice exploration on anatomy and function
* Genes expressed
** Should include some citations to support statements made e.g. in "current literature highlights..."
* Blood supply
** Be wary of plagiarism
* Developmental abnormalities
** Extensive but suitably brief
** Some efforts made to explore complications of the abnormalities discussed but could be expanded on further
* Current research
** If papers are going to be listed for viewer's further reading, brief summaries of their abstracts of content should be included
* Overall, solid effort and well-structured page. However:
** Minor grammatical errors present throughout page
** Intext citations should be checked thoroughly before final submission
** Remember to clear zIDs before final submission

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GROUP 2

Kidney: I would restructure this section to give a clearer introduction and description of the anatomy (and clearer heading) - this could occur just by switching around the order of some of the content. Images are well captioned. Timeline of Kidney Embryology/Kidney development: This section is great. I like the very concise timeline as an introduction to this section. The stages are well written and contain good detail (just watch out with that last section of blood supply which I am sure you will fix) Developmental abnormalities: I would give the first few paragraphs a bit more context through a heading - or going into greater detail with an example. Lots of good detail and good visual examples Current Research/Questions for the future/General info on the renal system: obviously this section will be completed more over the coming weeks

Overall: I would try and style the other sections of the page in a similar light to Kidney Development section which has a great format. I like the use of imaged throughout which add good value to the text. A bit more detail to be added to some sections but definitely on the right track

Talk:2017 Group Project 1

2017-10-12T05:26:38Z

Z3416557:

{{ANAT2341Project2017discussion}}



=Cerebral Cortex=
==Introduction==
https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0024757/ [[User:Z5177691|Z5177691]] ([[User talk:Z5177691|talk]]) 22:37, 23 August 2017 (AEST)

==Lobes and Function==
4 Lobes: parietal, temporal, frontal, occipital
Video Overview: [https://www.khanacademy.org/science/health-and-medicine/human-anatomy-and-physiology/nervous-system-introduction/v/cerebral-cortex "Cerebral Histology"]
[[User:Z5177691|Z5177691]] ([[User talk:Z5177691|talk]]) 22:32, 23 August 2017 (AEST)

==Neocortical Development==
Nature article: https://www.nature.com/nrn/journal/v9/n2/full/nrn2252.html [[User:Z5177691|Z5177691]] ([[User talk:Z5177691|talk]]) 22:57, 23 August 2017 (AEST)

===6 Layers===
Layers I, II, III, IV, V, VI (see [http://www.ruf.rice.edu/~lngbrain/Sidhya/ "Cortical Layer Review"] [[User:Z5177691|Z5177691]] ([[User talk:Z5177691|talk]]) 22:57, 23 August 2017 (AEST)

==Anatomy and Function==

to do:

-change from dot points

-add images

-references

-finish function information

===Cell Types===
http://www.ruf.rice.edu/~lngbrain/Sidhya/ [[User:Z5177691|Z5177691]] ([[User talk:Z5177691|talk]]) 22:57, 23 August 2017 (AEST)

==Abnormalities==
PubMed Article: [https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0024757/ "Developmental Disorders"] [[User:Z5177691|Z5177691]] ([[User talk:Z5177691|talk]]) 22:41, 23 August 2017 (AEST)

=Peer Reviews=

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This page is very well structured and sequential. It provides a very detailed explanation of development under chronological subheadings. Subpages under images are well informed, but some images lack a proper Copyright phrase and Student Image Template to indicate reproducibility. On the main page, some subheadings need to be capitalised (formatting) and student signatures need to be provided on relevant sections, rather than student numbers . The "Anatomy of the Cerebral Cortex" section is filled with dot points, and could be improved using paragraphs, images and Wiki formatting. The layout of the Abnormalities section could be improved, by changing the headings and subheadings. The images and videos on the page are all very relevant to the topic, but I don't think the screenshots from youtube are appropriate of reputable. The page could benefit from a glossary list and 'Future Research' section. However, the reference list was well constructed. Overall the the page addresses the brief very well.

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Be careful in how the sentences are expressed for example in the introduction ‘the cerebral cortex is actually the outermost layer’; avoid using ‘actually’ in this sentence. Don’t forget to remove the student numbers from the posts. Minor grammatical errors; no use of commas in long sentences. The images do include copyright however the team has forgotten to place the Student Image Template that is required. The team should add a small description of the images that are on their webpage so readers will see immediately what the image is showing. The team could do a further questions subheading or an animal model subheading to explore more on the research of the Cerebral Cortex.

Subheadings and content that have been used show a good understanding of the topic area. The use of dot points where necessary are done well which makes the project easier to understand and read through. The use of tables to demonstrate the ‘Timeline of Corticogenesis’ is done comprehensively; maybe an image for each day that is explained should be added to show consistency (as only the last row has an image). The team has used their own diagrams which shows that the team was innovative in displaying their research. The references used are cited correctly, however, there are links at the bottom where they need to fix up and place it under references.

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Overall, the page is has nice structuring making it relatively easy to follow. But they are missing major topics necessary including historical discoveries, developmental signalling processes, current research and animal models. The introduction was short and concise, which provided a relevant amount of background knowledge. The anatomy and functions of the cerebral cortex could be put before the development so that it ties in with the introduction. The images and videos were relevant to the topic, which aided in understanding the content. However, labelling, adding a description and citing is necessary for images and videos which has not been done. A table would be a great feature for the timeline because right now its annoying to read and has a messy, unfinished look. References need fixing.

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The page has good structure and formatting, however there is a significant unfinished touch. Anatomy of the Cerebral Cortex heading could place all the information in a table to make it easier to read as well as images to help the viewer visualise the process. Maybe remove the student numbers because they are unnecessary and make the page look not as professional. figures and tables need to be labelled as well as referencing and copyright claims. The diagram under the statement "Migration and division of all six layers of the cortex is completed during the third trimester. Each layer has distinct synaptic connections and cell types that contribute to the specific functions of the cortex." needs to be further explained because I had a hard time understanding the image and what each section meant. The video is a nice touch to help understand the function and placement of the cerebral cortex. Developmental abnormalities was well written, easy to understand and flowed nicely.

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Well-structured and provides a vast amount of background information on the functions and structure of the cortex before delving into the details of development. However, the anatomy of the cerebral cortex and the layers are difficult to understand due to heavy use of dot points – perhaps images would be of good use in this section. There is consistently limited evidence of in-text references or citations throughout the information (rather than at the beginning of some of the sections) which makes it harder to link or follow where information was gathered. Headings are concise and easy to follow however the “other info to add” subheading under “Anatomy of the Cerebral Cortex” needs to be reworded for efficiency. Under the subheading “A) Disorders due to …” the disorders are inconsistently numbered – a 2 needs to be placed with “Hemimegalencephaly” as well as 8 with Schizencephaly. Functions of the cerebral cortex is hard to follow as dot points are used with lacking descriptions or expansion. Perhaps further discussing the actions of each functional area would provide more sufficient information in this part.

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The layout is looking very good, pictures could be a little smaller. I like the choice of headings, they explain well what is going to be talked about. I feel like you need to add headings like animal models and current research needs to be fixed but I’m sure that’s what is intended. I have some minor points for some of the headings:
Early development:
Spelling: Rhomboncephalon, and the instead of three at the beginning of a paragraph. Overall this heading was covered well
Development of cerebral cortex:
With images, you can add figure titles and this could make your page flow better!! Maybe expand a bit more on the key developmental zones in the human cortex, a brief explanation of what happens could help. The table is very well explained, however for E50-55 I can’t see a reference for all the information, also for the picture in the table for E50-55, you haven’t copied the copyright information so you should add that so it can be used in the page and also add the student template. I really like the drawn picture, but again a figure description would be helpful. This section is very well done.
Anatomy of the cerebral cortex
Some great points but needs to be broken up into paragraphs. Your Wikipedia link for the image is a good image however you should find the original, I recognize it from Cajal’s drawings so I think it could be in a paper about the cerebellum with Cajal. You have good ideas for this heading, also maybe add another image.
Functions of the cerebral cortex
For functional areas, I think a 2 sentence description of each area would be good and maybe a picture for reference.
Abnormalities
Intext referencing would be better. For images, add the student template to each!! Im not entirely sure how I feel about the youtube screenshots as images, maybe use one but try and find some in research articles aswell.
Overall, I think you’ve done a really good job at summarizing abnormalities.

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The introduction was a good opening to the Cortex page as it gives a brief overview and understanding of the cortex generally. The next subheading, “Early development of the Brain”, provides of a simple and clear explanation of the early development process however images would be a great addition to help visualise the text. Try having a look at some images that were shown to us in previous lectures on the brain development where it showed the neural plate, neuroectoderm and subsequent developments.
The next subheading, “Development of Cerebral Cortex”, would probably do better to be called “Later Development of Cerebral Cortex” as it would be a seamless flow from the previous subheading of “Early development…”. It was good that a labelled image was used and information was added for explanation. It helped orient me as I was going on to read about the timeline of corticogenesis. The timeline was detailed and the use of bold helped highlight key terms. However, I would suggest making another column for images on each day. Visual reinforcement just makes the information easier to absorb and make more sense.
The subheading, “Anatomy of the Cerebral Cortex”, is clearly in the editing process. I would just once again definitely recommend the use of images in this section, both hand-drawn diagrams and labelled images from the internet. I thought the use of a video was a clever way to cover the cerebral cortex functions. A bit of general text that briefly covers the functions of the main parts would be a good addition in this section, as a segue into the video.
The “Abnormalities” subheading was a good balance of text and images. It was easier to read because it was split into categories. I would only suggest that you mention at the beginning of the section that abnormalities associated with the cerebral cortex development can be divided into the following categories… I can see the references were placed at the beginning of the section and I’m assuming that is temporary. It is better if they are dispersed within the text where appropriate. There are a good bunch of references but you could probably aim for 25-30 for this page.

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This page needs some more information about current research, signaling processes, future questions and references to animal models. It would also be good with a table or quick overview of developmental origin. There has been a good use of pictures and tables. The setup of the section about abnormalities is really good. This page needs to use more references during the sections and not only at the start of a section. A glossary list would also be good for the reader to understand the page.

*'''Introduction''': Gives a quick knowledge of the cerebral cortex. A picture would be good to support this introduction and maybe a bit more description of the different terms. This section also needs references.
*'''Early Development:''' Good setup with bulleting. I find some of the context a bit confusing to read - especially these two sentences "From there three primary vesicles, there is a further division at the anterior extremity of the medullary canal into five secondary vesicles during week five" and "During the fifth week, the embryonic brain undergoes rapid growth folding the neural tube and consequently resulting in three brain flexures" Maybe you can rephrase this.
*'''Development of Cerebral Cortex:''' Good section! Good overview.
*'''Timeline of Corticogenesis:''' Please give a short introduction of what Corticogenesis and Neurogenesis means. Good picture supporting the E50-55, maybe you can put this picture already in the section called "Key developmental zones in the human cortex" since this is the first time we get introduced to the different zones and plates and it would give a better basic knowledge before getting into Corticogenesis.
*'''Anatomy and Function of the Cerebral Cortex''': These two sections should maybe be earlier on the project page together with the introduction since it's a basic understanding of the Cerebral Cortex. Both sections look a bit messy, try to work on making it more simple and easier to read - it kind of looks like personal notes and not a proper information site :-) These sections also need some references. The video in this section gives a good understanding. Good idea putting a video on the page.
*'''Abnormalities associated with Cerebral Cortex Development:''' This section is really good. Great overview of the different scenarios and a lot of pictures to support the reading. Instead of mentioning all the references in the start of the section, you should add the specific reference used for each subsection, this will make it easier for the reader to look up references for specific sections.

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In the introduction section, it was not referenced where the information facts are from. This section should introduce a brief information on the topic, what you are going to discuss on the whole wiki page, introduce current researches and animal models to support the new findings and understandings. Also, don't use "actually" in the sentence.
On the page, It is better to write in full sentences instead of dot points as I've seen a lot of them and include any of scientific words in the glossary section at the end of the page. Where you've inserted picture, it will be clearer to also include it within the text in brackets for example (Figure 1).
Any figures or pictures on this page needs references as well.
In the abnormality section, it is well written with supporting pictures, but in my opinion, it is easier to read if the the figures/pictures are on the same side and texts on the other side instead of alternating. This section was very thoroughly referenced too. I think a small paragraph under the heading introducing the different type of disorders before going into greater details.
Don't focus too much on the anatomy as I can see this section is not finished nor written in paragraph and no pictures or figures, would be better to swap anatomy with some other embryology discussion for example, signalling processes.
Touch on current researches, animal model if any and future questions as they were not seen on the page. Also include a glossary table. References section is looking good but more is needed.

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Overall, a really informative and well-written wiki. The information was well presented and was understandable. The abnormalities section of the wiki, was particularly well done, as it was a good idea to group each abnormality with the disruption of the main event that lead to the abnormality, as it informs the reader that different abnormalities arise from a disruption of different processes that occur in the development of the cerebral cortex. The diagrams and pictures were useful as it functions as a reference point.

Overall, the layout was good, however maybe use more of a dot-point layout in the Anatomy section and maybe add some diagrams of pictures to enhance the information given. Also the sub-title "what is it?" is probably not needed as the introduction itself suggests that you will be describing what the cerebral cortex is and what is does. The Functions of Cerebral cortex may also need a bit more text as the video should just be a supplement rather than the main source for information in that section. Overall, well done as it was an informative and well written wiki.

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Overall I find the information provided to be concise and easy to understand. The introduction was great in giving us a brief overview of page. The layout of the early development of the brain and the development of the cerebral cortex was really nice. I like the use of bullet points as this makes it easier to read. Also good amount of referencing is seen in this area. The use of the table is also a nice touch to the page and I like the picture used for E50-55. However, it could help to have another column with pictures for each row. That would help with the understanding of the text. For the anatomy of the cerebral cortex, it seems a little messy and hard to read as it is too point form. Perhaps these could be phrased into proper sentences with certain parts placed into bullet points to make it easier to read. Also, with the anatomy, pictures would be very helpful to aid in the explanation. For the functions of the cerebral cortex, it lists the functional areas but not the functions of those areas. Although it is stated in the video, which is a nice addition to the page, this could be improved by adding short sentences that state these functions that were mentioned as well. For Sections 1.4 and 1.5, references are also needed to state where the information was obtained from. The abnormalities section provides detailed explanations of the various disorders associated with the development of the cerebral cortex. There is also a good amount of pictures used. One thing I noticed was the references which was placed on the top of the section instead of throughout the text.

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Overall, the page has a good structure and flow with good headings and subheadings. The information provided was concise and easy to comprehend. The introduction provides a brief overview and sufficient background knowledge about the cerebral cortex. I like how the team thought of mentioning about the early development of the brain before narrowing it down to the cerebral cortex. However these two sections do not seem to flow well. Maybe you could have 2-3 sentences that could help ease into the development of the cerebral cortex. I really love the timeline of corticogenesis. This part has been done really well. One minor improvement that could be made is to add images under each embryonic stage instead of just the last stage to better aid the reader into understanding the development. Also, a brief description of what corticogenesis is could be included before the table. For these two sections, there were a good amount of references.

For the anatomy of the cerebral cortex, it seems a little messy and hard to understand as its written in point forms. Perhaps, the dot points could be changed to proper sentences with histological images to tie it together. For the functions of the cerebral cortex, I think you could use a table to list down the areas and then provide a brief description of the functions of that particular part. The video is a good addition to the page. These two sections are lacking citations and references.The abnormalities section was well done. However, the citations should be added within the text instead of at the top of the page. Since there are a lot of abnormalities, maybe the team could list in a few sentences about all the abnormalities that they are going to discuss to have a better start to the section. For the images that are used on this page, the images should be labelled as “figure 1” or “table 1”. Maybe, sections on the “animal models” and “current research” could be added to wrap the page up.

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Overall the project was very good and clear. Pictures were well placed and bullet points spaced out information, making the page easy to look at and follow. The layout of the beginning and end sections with the short paragraphs and interspersed bullet points broke up the information and highlighted key facts. The introduction was a good overview of the page, including a quick summary of the anatomy, function, and development of the cerebral cortex.

There were some basic grammatical and spelling errors (e.g. “neurons” is spelled wrong under the subheading “Layer 4”), but for the most part did not take away from the clarity of the page. One sentence, “From there three primary vesicles, there is a further division at the anterior extremity of the medullary canal into five secondary vesicles during week five,” seems to be missing something at the beginning that would increase clarity.

Some pictures had a lot of information in the summary when clicking on them while others lacked sufficient information. Some pictures that could benefit from more information are Corticogenesis of mouse and humans.jpeg, SBH.png, Disorders of Cortical Formation2.png, Symptoms of microcephaly.png, Hemimegalencephaly.png, and SchizencephalicBrain.jpg. These pictures are relevant to the topic and are pretty self-explanatory so this does not take away much clarity from the page but for the parameters of the project, additional summary should be added. The picture Stage22 HPA2L.jpg has good information in the summary but it is oddly structured. FASface.jpeg does not have any copyright information included. Having Gray754.png displayed on the page rather than as a link would look better.

The video describing the functions of the cerebral cortex was a good introduction to that topic. The video was easy to watch and understand. The first video about corpus callosum agenesis was a good introduction to the topic, but the second video about corpus callosum agenesis was long and the lecturer was hard to understand. That subheading would benefit from a brief description of that topic rather that a long video explanation.

The switch from a mix of bullets and short paragraphs to all bullet points in Anatomy of the Cerebral Cortex makes the page look less cohesive. The last bullet point in Layer 4 is hard to understand and the last 2 bullet points in Layer 5 would flow better if they were combined. The information in these sections are good and relatively easy to follow.

Overall the project is very good. The table explaining the timetable of cortex development is a clear way to break down the topic. Breaking down the information of abnormal development into what went wrong in the embryology (e.g. migration problems vs. differentiation problems) highlights importance of embryology in congenital disorders. There is a lot of information about the abnormal development of the cortex but could use some information about past and current research and animal studies. Reference list at the end looks good but the in-text citations of abnormal development should be interspersed with the information rather than all at the beginning.

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*Overall, the page is well structured and relatively easy to follow with the headings and subheadings relevant to the topic area (embryology of the cerebral cortex).

*The introduction was short and concise, which provided a relevant amount of background knowledge before delving straight into the development.

*Perhaps the Anatomy and Functions of the cerebral cortex could be put before the development so that it ties in with the introduction.

*The use of dot points under Anatomy and Function of the Cerebral Cortex was excessive and gives off an unfinished feel. Perhaps you could add in a couple of images to make these dot points easier to understand. Also, it might be better to use the * function to create these dot points.

*The use of the table on the "Timeline of Corticogenesis” was quite clever and made it easier to understand, however I suggest that you add photos in E30, E31-32 and E40-45 since there seems to only be one photo in E50-55. The page is lacking a "further questions" section which would be quite informative in understanding the research gap to date.

*I think the Disorders was nicely done and was very informative. The use of images in the left and right side of the page made it aesthetically pleasing to read. However this section lacks references, which I think you should add to avoid plagiarism.

*The images and videos that are on the page are very relevant to the topic, which aided in understanding the content. However perhaps you could label them using "Figure 1", or "Table 1" etc as well as putting an appropriate description under the image/video. Also, the link of an wiki image under Layers was not inserted properly, so be sure to check that for next time.

*References were inconsistent throughout the page, however most were done properly.

----
The chosen headings for the development of the cerebral cortex were very suitable to highlight the key topics in providing a page of summarised information. It was then easy to navigate through the page using the shortcuts and finding information. Although, there was one sub sub heading “Timeline of Corticogenesis” that was formatted to be in bold while the rest were not.

The disorders listed seems to be really interesting and it covers the whole spectrum of the case abnormalities. But I suggest to get rid of the letter bullets (e.g. A), B), C) ) for the breakdown of the abnormalities.

The introduction had a quick and concise text, however, an image of the cerebellum would be suitable in this section on the side. While the sub sub heading stated that the introduction section will talk about the features of a cerebellum, a paragraph about the development and its stages were written down in this section as well. This could be moved into the ‘Early Development of the Brain’ subheading underneath. Bullet points of the brain layers as well as a diagram would be helpful for the visualisation of the brain.

For the sections that explain the development in specific weeks, a table would be advisable to make it neater and easier to look at. Also, an image was left inside the table grids and it was confusing whether it was meant to be there or not. Perhaps adding a photo gallery showing the stages at the bottom of the table would be better.

Hand drawn diagrams were really precise, neat and was very visually appealing. It was taking up all the space and unless it is intentional, I suggest to resize the drawing into a smaller one that fits the page as well as the accompanying text and content of the drawing.

The variety of visual aids were really entertaining and were referenced properly.

Finally, the reference list at the bottom of the page did not have a consistent format. It was mostly APA format however the others looked like a different format.

---

The most obvious flaw was the lack of polish in formatting of some of the page. Bullet points are only so useful when it comes to writing a wiki page, instead of taking notes. The page is unfinished, but, the content included especially in the "Development of Cerebral Cortex" and "Abnormalities associated with Cerebral Cortex Development" was extensive and well done. The large table that linked the development with the time period was very useful and the choice of bolding key words allowed the main idea in the paragraph to be quickly understood from a glance. The use of images very much enhanced the descriptions and checker-like the layout of the different abnormalities was refreshing. Some subheadings, such as the Anatomy and Function of the cerebral cortex, could be elaborated on but the overall structure of the page is logical and fluid, and the writing is clear and concise without being superficial.

--- 
Strengths: 
• The page has an excellent structure covering a broad variety of topics regarding the cerebral cortex. It was great to see how you also explored abnormalities associated with the cerebral cortex. Furthermore the use of various subheadings and headings related to cerebral cortex development meets criteria 1 and 2 of the assessment. 
• The presentation of the wiki page was excellent in that a variety of images, videos and tables were utilized. The use of such sources of information helps present information in a much more clear and concise manner, whilst also providing a thorough explanation to visual learners. Hence the wiki page has an element of teaching at a peer level (criteria 4 is satisfied). 
• A large number of references have also been included within the wiki page, a characteristic which helps increase the reliability of information presented. Furthermore, most sources are recent which another great characteristic. Thus, it appears that the group has satisfied criteria 3 for the assessment. 
• Each topic appears to show a significant amount of detail which is excellent. In addition, the use of images alongside the text is a great tool as the audience is able to better visualize the concept being described. 

Areas of improvement: 
• Although you have provided a variety of recent references, to improve you may avoid using sources as old as 1977 as results presented from this study may be outdated. 
• It was excellent that the functional areas of the brain were listed, however to improve you may wish to elaborate on the specific functions of these areas. You may also explore how abnormalities of these areas during development may impact upon the behaviour of the individual following birth 
• Whilst a variety of topics have been covered, you may wish to also describe the importance of signaling throughout the process of cortical development. For example, you may investigate different growth factors and receptors involved in the process. 
• Another possible improvement would be to perhaps include a timeline of different researchers who contributed to the in-depth understanding of the developing cortex that we have today. You may also describe what each researcher discovered. 
• In order to completely satisfy criteria 5, you may wish to conduct further research beyond the scope of formal teaching activities. For example you may explore the contribution of animal models towards our understanding of cortical development. 

----

This peer review is based on the relevant dot points of the ‘Group Assessment Criteria’, as well as subheadings suggested by Mark. This information can be found on the student page.

{| border="1" align="left"
|-
|Criteria
|Strengths
|Weaknesses
|-
| 1. The choice of content shows a good understanding of the topic area
| The developmental origin of the cerebral cortex is addressed well under the sub-heading ‘Early development of the brain’.

The development timeline of the cerebral cortex is described clearly and in detail in the table of the ‘Timeline of corticogenesis’.

Abnormal development of the cerebral cortex and the associated conditions are covered in an immense amount of detail. The accompanying images and videos enhance the written information, as well as making it easier for the reader to comprehend. In addition, the sub-headings of this section compartmentalize the congenital diseases in a logical manner that highlights the link between abnormal development and specific diseases.
| There are several key topic areas missing from the page:
*There is no section covering key historical discoveries relevant to the cerebral cortex and its embryological development.
*There is no information relating to developmental signalling processes
*There is no section on current research in fields relevant to the embryological development of the cerebral cortex.
*There is no section on animal models that have been used to advance scientific understanding of the cerebral cortex.
*There is no section on future questions regarding the development of the cerebral cortex.
*A glossary of terms has not been included.

Some sections that have been included are somewhat irrelevant to the subject matter. For example, there is a large (unfinished) section on the anatomy and functions of the cerebral cortex. While it is important to provide a bit of an anatomical background on the subject, it shouldn’t be a major focus of this assignment. Focus more on the sections mentioned above, and keep the project focused on the embryology of the cerebral cortex.
|-
|2. Content is correctly cited and referenced
|There have been attempts at referencing throughout the assignment. A reference list has been produced and appears mostly correct. References have not been repeated throughout the list.

Peer-reviewed primary research articles have been used in this assignment.

The student-drawn image has been cited correctly, as have most of the images used in the ‘abnormal development’ section.
|Overall, referencing in this assignment is very poor. Most of the content is completely devoid of any references (see ‘introduction’, ‘anatomy of the cortex’ and ‘abnormal development), and sections that have been referenced have been referenced “by paragraph” (see ‘timeline of corticogenesis’)

Many of the sources used in this assignment are inappropriate and/or unreliable. Try to rely more on primary research articles and less on textbooks or websites.

Many of the images have been cited incorrectly and used without permission. Remember to include the full reference, the original summary and the copyright license information for each image.
|-
|3. The wiki has an element of teaching at a peer level
|The information presented is mostly at a level appropriate for peers. Images and hand-drawn diagrams have been included to facilitate the readers understanding of the subject matter. Some of the images contain useful descriptions of the subject matter, and aid in understanding of the topic.
|Many of the acronyms and terms used in this assignment are not well explained. Include a glossary of terms to make some of the content easier to follow and understand.
|-
|4. Relates the topic and content of the Wiki entry to learning aims of embryology
|The development of the cerebral cortex was covered extensively, which is a very important learning aim of embryology.
|There are certain learning aims of embryology that have not been included in this assignment, such as developmental signaling processes (see criteria 1 for more information). There has been no discussion of relevant historical or current research (adding in the subheadings “key developments” and “current research” would help rectify this).
|-
|5. The content of the wiki should demonstrate to the reader that your group has researched adequately on this topic
|Certain aspects have been researched and presented well (such as embryological development).

Links to other pages of the UNSW embryology wiki have been included, however they have been used as references rather than just links.
|Information from the UNSW embryology wiki has been used as direct sources of information. Instead they should be included to relate this particular wiki page to other areas of learning.

The small number of sources cited in the reference list demonstrates a poor and narrow approach to researching this topic. A greater library of sources should be used to create this page (mainly primary research articles).
|}

Grade: FAIL

General Comment:
While some aspects of the wiki page have been done well, the page is largely unfinished. Many sections still need to be added, and others are in need of improvement.

----
The introduction of this page gives a good general background but could benefit from adding bullet points to describe the six horizontal layers of the cortex and maybe a short summary of its clinical significance. 'Early Development' was well written, easy to follow and well referenced. 'Development of Cerebral Cortex' would benefit from a short introductory statement instead of going straight into the 'Main classes of neurons'. Pictures and tables in this section were informative and engaging to the reader. Hand-drawn picture was well done, colourful and easy to interpret. 'Anatomy of the Cerebral Cortex' looks unfinished and isn't easy to read as it doesn't flow or show a clear structure. No references can be seen and no pictures or tables to make for easier reading or understanding. The different layers of the cortex would greatly benefit from a table with structure/function format or a clear diagram. The same is true for 'Functions of the Cerebral Cortex'. 'Abnormalities associated with Cerebral Cortex Development' I liked the setup of this section because of its clear headings and subheadings as well as its informative pictures. The captions on some of these pictures need to be elaborated on. Also couldn't see any in text referencing which really needs to be present. Content is clear and concise and easy to follow. This section was engaging and well done. 'INFO/Research Links' was not finished yet but shows lots of research articles that could be promising.
----

'''Peer review project 1:'''

I have some general comments which applies to almost all of the sections in the project:
* The referencing is not proper. A lot of the sections do not have reference or all of the reference are at the bottom of the section.
* Some of the sections have bullet points instead of text. It feels like you are reading somebodies notes not a project.
* It would be nice with more pictures to get a better understanding. The pictures there are good, but it does not have any caption. The size is to big as well for some of the pictures (the drawing with the mouse and human model)
* The project does not have a current research, future questions section or animal, which is a requirement for the project.
* I think it would be better for the project if the anatomy and function sections stood before the development part. It would give a better understanding or at least I think so.
* In general, I don’t feel like the project is connected, and expressions like cortigenesis and neurogenesis is not defined.
* I really think the timeline is nice. But a lot of the text within the timeline would have been more appropriate to write in the cortex development section. It should contain some key discoveries instead. But the text there is good, makes sense to me and is well written.
* In the early development of the brain section I don’t understand some of the sentence like: “From there three primary vesicles, there is a further division at the anterior extremity of the medullary canal into five secondary vesicles during week five. These are fundamental divisions of the adult brain and communicate freely with each other”. Some of it should properly be rephrased.
* There are some repetions during the project. The text could be compromised.
* In general, the language is neutral and written in a good scientific way.

----
- Covers only development, anatomy, functions and abnormalities, more subheadings could be better and exploring other areas of the embryology of the cerebral cortex

- Nice introduction that summarises what the cerebral cortex does and some of its structural layers. Would be nice to see a diagram with the layers of the cerebral cortex or a diagram of the cerebral cortex in the introduction.

- Development of the brain was covered really well and was detailed and also proper and good amount of referencing in this section. Good use of lot of pictures in this section, which made it much easier to understand.

- Timeline of corticogenesis was explained very well in a straightforward manner and use of the table helped.

- Anatomy of cerebral cortex as well as functions of the cerebral cortex is still incomplete and is mainly in dot points and no referencing

- Abnormalities was done well and very detailed and covered many types of abnormalities. Disorders were also divided into categories which is good.

- Good use of pictures in the abnormalities of the section for each abnormalities but use of videos were probably not necessary in this section

- Overall, introduction, development and abnormalities were all done well and good grammar and spelling. Other main headings definitely needed more work and referencing was done incorrectly or absent in some parts. There could be more subheadings and there is no glossary.

- References are from proper journal articles/peer reviewed journals which is good.

----

- Introduction provides a good summary, however the list of layers is quite long so maybe adding a diagram would make all that information a bit easier to take in? Or perhaps, listing the layers in dot point form rather than a long sentence.
- Early development of the brain is very detailed, well researched as evidenced by the many references. Perhaps a short table summarising all that information could be added. Some formatting issues, but nothing that can't be easily fixed.
- Development of cerebral cortex section very well done. Good use of diagrams and the table; they made the information easier to understand. However maybe the drawn diagram could be smaller (good job though!). Easy to follow.
- Anatomy and functions sections are obviously unfinished, but it is clear that extensive research has been done to produce all that in the first place. So good job, once it is all formatted, I'm sure it will look great. All the dot points were easy to understand anyway.
- Abnormalities section was very well researched. Great use of diagrams. Personally, I found the subheadings easy to grasp in the Contents, however it was a bit overwhelming to scroll through it all.

Overall, a good job. It is clear that some sections are incomplete, but it seems like there is a clear direction of where it is going. I would recommend a glossary of terms, just because the cerebral cortex is so complex and all the terms can become overwhelming. Tables in the development would help with this also just to provide a quick and easily accesible summary of development.

----

* Introduction
** Could have been linked together with anatomy and function for better structuring of page
** Simple diagram could have been used to provide context on body location
* Development of the cerebral cortex
** Section should be expanded upon to give context to the content
*** Seemed like a sudden introduction of neuronal classes and key developmental zones without much expansion
** Section seemed to be more about components of the developing cerebral cortex rather than development itself – could update subheading to reflect this or update content to focus more on development
* Timeline of corticogenesis
** Could have been its own subheading
* Anatomy
** Should be moved up towards start of the page with introduction
* Functions
** Should be moved up towards start of page with introduction
** Functional areas should be expanded upon to briefly discuss their different roles
** Should not rely too much on linked video
* Abnormalities
** Diagram “disorders of cortical formation” gave little information relating to section – seemed like illustration related little to the mentioned stages. Instead, could have mentioned that abnormalities arise during proliferation, migration and organisation during cortical development
** Lettering and numbering of subheadings in this section should be switched for clarity
* Overall was well done. However:
** Some diagrams lacked descriptions and figure legends/abbreviation definitions – diagrams should be self-explanatory and be understandable in combination with their descriptions, when taken out of their contexts within the page
** Minor grammatical errors present throughout the page
** Mostly well-structured but some subheadings can be shifted around - see above for specific feedback
** Remember to clear zIDs before final submission

----
*Introduction
**References are missing.
**Labeled images could be included to illustrate the relative position of cerebral cortex and cerebrum in the human brain and the organization of cerebral cortex into the six horizontal layers.

*Early development of the brain
**Written expression could be clearer. For example, L1: “The brain begins to develop during the third week (of pregnancy) when the neural plate and (neural) tube (are derived) from the outermost layer of embryonic cells, (that is) the neuroectoderm.”.
**A table listing the major development occurring at each week (i.e. week 3 – start of development of brain, week 4 – fusion of the neural folds) could be included for easier understanding of the developmental timeline
**Labeled images should be included for clear illustration of the relative positions and development of various parts of the cerebral cortex.

*Development of cerebral cortex
**Appropriate inclusion of images that aid in understanding the content. However, there is little reference or explanation to the images in the text. No caption is included for the images. The first image and the second image are redundant to each other as they are both illustrating the key developmental zones in the human cortex. Author may want to consider taking one of them out.
**Good use of a table in summarising the developmental timeline for corticogenesis. Clear explanation of corticogenesis.

*Anatomy of the cerebral cortex
**Content could be better organized in paragraphs instead of point forms.
**Labelled images should be included for clear illustration

*Functions of the cerebral cortex
**More content could be added to each of the functional areas listed.
**Video is appropriate and useful in facilitating understanding.

*Abnormalities associated with cerebral cortex development
**References should be included where appropriate instead of generalizing as “references used to write”.
**The amount of content seems slightly overwhelming as compared to other sections of the page which are equally important as well. Nonetheless, good effort in explaining the abnormalities in great details.
**Some references are missing.

*References
**Good effort in for having both journal and book references. However, it would be good to adhere to either APA or BJP style of referencing.

__

GROUP 1

Early Development of the Brain: Well written, maybe a little concise, there are some great images which could be useful for this section also Development of Cerebral Cortex: Lots of good information, maybe try to make this section a bit more fluid - comes of a little disjointed Anatomy of the Cerebral Cortex/Functions of the Cerebral Cortex: This section does not read well to the eye - that's not to say it is incorrect - I would try putting this into a friendly format Abnormalities associated with Cerebral Cortex Development: This section is huge, but each condition has a fairly concise explanation so well done

Overall: There is lots of sound information on the page - main emphasis would be giving the page a clean up of the format and trying to make the sections flow together a little nicer

User:Z3416557

2017-10-12T03:39:25Z

Z3416557:

{{ANAT2341ProjectGroup2017table}}

[[File:Chicken embryo E-cad and P-cad gastrulation.png|500px]]

Chicken embryo E-cadherin and P-cadherin in gastrulation<ref><pubmed>27097030</pubmed></ref>

Here is the [[Student Page]] demonstration page I showed in the Practical class.

Use this page to practice editing and don't forget to add a topic to the [[2017 Group Project 4]] page.

 
{{2017ANAT2341 footer}}

[[Student Page]]

__

GROUP PROJECTS - PEER REVIEW

GROUP 1

Early Development of the Brain: Well written, maybe a little concise, there are some great images which could be useful for this section also
Development of Cerebral Cortex: Lots of good information, maybe try to make this section a bit more fluid - comes of a little disjointed
Anatomy of the Cerebral Cortex/Functions of the Cerebral Cortex: This section does not read well to the eye - that's not to say it is incorrect - I would try putting this into a friendly format
Abnormalities associated with Cerebral Cortex Development: This section is huge, but each condition has a fairly concise explanation so well done

Overall: There is lots of sound information on the page - main emphasis would be giving the page a clean up of the format and trying to make the sections flow together a little nicer

GROUP 2

Kidney: I would restructure this section to give a clearer introduction and description of the anatomy (and clearer heading) - this could occur just by switching around the order of some of the content. Images are well captioned.
Timeline of Kidney Embryology/Kidney development: This section is great. I like the very concise timeline as an introduction to this section. The stages are well written and contain good detail (just watch out with that last section of blood supply which I am sure you will fix)
Developmental abnormalities: I would give the first few paragraphs a bit more context through a heading - or going into greater detail with an example. Lots of good detail and good visual examples
Current Research/Questions for the future/General info on the renal system: obviously this section will be completed more over the coming weeks

Overall: I would try and style the other sections of the page in a similar light to Kidney Development section which has a great format. I like the use of imaged throughout which add good value to the text. A bit more detail to be added to some sections but definitely on the right track

GROUP 3

Introduction: Well written and concise - sets up a good expectation of whats to come
Developmental Origin: I like how you have referenced the images in the text - though I would try to fix the image placement (it's hard - I am struggling also!)
Developmental Timeline: This section is excellent - great amount of detail, well written, and great supporting images
Developmental Signalling Processes: Also a very good section (just keep writing how you have for the rest of the subheadings!) - also need to fix up the referencing of that 2nd image
Current Research And Findings: There is a commendable effort here to summarize current research. I might be nitpicking here but maybe try to make this section a little more concise as it is large blocks of text
Glossary of Terms: Useful section to include

Overall: The level of research and depth of writing of this page is excellent. There isn't too much to change - and if the rest of the subheadings left to complete are in the same style as the rest of the page I think you guys should be pretty happy!

GROUP 5

Lung Anatomy/Histology/Cardiovasculature: I think this section is an excellent start to your groups page - the histology section especially adds some depth. The drawings are really nice to view too!
Developmental Origins/Timeline: the table is really well structured and there is a nice amount of depth in the description. I like the inclusion of historical developments also
Structure/Developmental Signalling: This section flows nicely on from the previous subheadings and is also well written. However there is a lack of referencing in both of these sections
Abnormal development: again a good amount of depth and well written.

Overall: not much to fault with this project it looks like you guys are on the right track!

Group 6

Introduction: I think this is a good idea but I would try and make it a bit more concise/general
Basic Anatomy/Microanatomy: I like the way you have described the anatomy through description of pictures - it is very clear to understand and i think it is well categorised with an apt amount of information on each section
Vesicles/Cerebellum Development: there is a great amount of detail in this section but I would work to make it more readable especially with the large chunks of text in the cerebellum section
Cell Signaling: this section is well categorised and well referenced
Timeline: good use of images here

Overall: a well researched a referenced page. Only comments would to try to make some sections concise and consider how each section flow into each other

User:Z3416557

2017-10-12T03:29:29Z

Z3416557:

User:Z3416557

2017-10-11T04:16:04Z

Z3416557:

2017 Group Project 4

2017-10-05T03:59:55Z

Z3416557:

{{ANAT2341Project2017header}}

= Eye Development =
[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 16:09, 14 September 2017 (AEST) OK Feedback
* Timelines
* Embryonic contributions from germ layers and neural crest
* Cellular components
* Current research areas
* Get rid of the bold formatting for sub-headings.
* Animal models compared to human development
* Central neural pathway

== Anatomy of the Adult Eye ==

The eye is a complex sensory structure which allows a variety of species to intake and process visual information from the world around us.

To discuss the key anatomical components of the eye, we will break down the eye in parts<ref>Chen, J., 2011. Handbook of Visual Display Technology. Springer Berlin Heidelberg. Chapter 2.1</ref>:

'''Supporting Structures (Orbit, Extraoccular Muscles, Lacrimal Gland, Eyelid)'''
[[File:22292144 10208413540209536 722417340 o.jpg|250px|thumb|right]]
The orbit of the eye consists of a framework of bones and connective tissue which provide structural support and protection to the sensitive human eye. 7 bones contribute to the orbit of the eye: frontal, lacrimal, sphenoid, zygomtatic, ethmoid, maxilary, palatine. Several openings exist in the orbital structure, 2 key fissures are the superior orbital fissure and inferior orbital fissure and the posterior optic canal. These openings allow crainial nerves passageway.

A set of 6 extraoccular muscles allow for a strong voluntary control of the movement of the eye. These muscles include superior recuts, inferior rectus, lateral rectus, medial rectus, inferior oblique, superior oblique muscles. These muscles are some of the smallest in the human body and are designed to produce fast, controlled motion to focus on an object of interest.

The eyelid is the anterior covering of the eye, consisting of a thin fold of skin. It is controlled by the levitator palpabrae superioris muscle. Superio-laterally to the eyelid is the lacrimal gland, which serves to create a film of tear, an important component to keeping the anterior surface of the eye moist. The eyelid assists in this process by opening and closing, or blinking, which spreads the tear film across the surface of the eye. Tear film and debris caught in the tear film are excreted through the lacrimal duct which is located on the infero-medial surface of the eyelid.
[[File:22251179_10208414266827701_870733039_o.jpg|250px|thumb|right]]

'''Layers of the Eyeball (Sclera, Choroid, Retina)'''

The superficial layers of the eyeball is the sclera, a thick fibrous layer which becomes thicker as it extends posteriorly. The sclera is the visible as the white part of our eye. It's function is to provide structural stability to the eye and serves as attachment for some extraoccular insertions. Deep to the sclera is the choroid, a vascular network which provides nourishment to the layers of the eyeball and plays a large role in the growth of the eye. Deep to the choroid is the retina, a network of nerve fibers which transmit visual information. The retina contains 2 types of photoreceptors which convert visible light into nerve impulses. Rods work best in low light environments while cones work best in high light enthronements and detect colour and sharp detail.<ref>Curcio CA, Hendrickson AE. Organization and development of the primate photoreceptor mosaic. Prog Ret Ret. 1991;10:89–120.</ref>: The retina does not extend to the anterior part of the eyeball, unlike the sclera and choroid layers.

'''Anterior structure (Lens, Cornea, Pupil, Iris, Ciliary Body, Conjunctiva Anterior Chamber)'''

The most anterior component of the eyeball is the cornea, which is a multilayered avascular transparent structure who's major function to the refract light to assist image formation (contributes about 75% of total refraction). Continuous with cornea superiorly and inferiorly is the conjunctiva. Deep to the cornera is the iris, or the coloured ring visible in the eye. The iris consists of 2 muscles which act to enhance and diminish the size of the pupil, a hole in the middle of the iris allowing light to enter the eye. Deep to the pupil and iris is the lens, which is a transparent structure which contributes the other 25% of the eye's refractive power. The lens changes shape through accomodation controlled by the ciliary body muscles. The ciliary body is the anterior extension of the choroid. The function of the lens is to focus images by changing refractive power based on the position and depth of focal objects. In between the anterior surface of the lens and posterior surface of the cornea is the anterior chamber. This chamber is filled with aqueous humor supplied by the ciliary body, who's function is to provide nutrients to ocular structures and maintain intraocular pressure.
[[File:22251314_10208414283908128_862494115_o.jpg|250px|thumb|right]]

'''Posterior structure (Optic Nerve, Optic Disc, Macula, Fovea, Posterior Chamber)'''

In the posterior section of the retina is the macula, a central spot in which a high concentration of cone photoreceptors are found. The direct centre of the macula is called the fovea which contains solely cone photoreceptors. The fovea is only part of the eye which can conduct 'perfect' 20/20 vision. It has a high workload and hence a strong vascular supporting structure<ref><pubmed>6462623</pubmed></ref>:. The most posterior part of the eye is the optic nerve (along with the central retinal artery and central retinal vein), which is responsible for transporting nerve impulses to the cerebral cortex for processing. The opening of the optic nerve is called the optic disc, which contains no photoreceptors and is a blind spot of the eye. Between the posterior surface of the lens, the retina and the optic disc is the posterior chamber. The posterior chamber contains a vitreous humour, a jelly like substance with a high viscosity.

==Overview of eye development==

=== Timeline of embryonic development ===

{| class="wikitable"
! style="background:#f4a941" | WEEK
! style="background:#f4a941" | DEVELOPMENT
|-
| 3-4 || Eye fields, Optic vesicles
|-
| 5-6 || Optic Cup, Lens Vesicle, Choroid Fissure, Hyaloid Artery
|-
| 7-8 || Cornea, Anterior Chamber, Pupillary Membrane, Lens, Retina
|-
| 8-10 || Eyelids
|-
| 9-15 || Iris, Ciliary Body
|}

=== Carnegie Stages ===

Carnegie Stages is a system of 23 stages used to describe developmental events of the vertebrate embryo. At stage 10 we see early signs related to eye development <ref><pubmed>7364662</pubmed></ref>.

{| class="wikitable"
! style="background:#f4a941" | STAGE
! style="background:#f4a941" | EVENTS
|-
| Stage 10 (22 days) || The optic primordium has developed. Two small grooves develop on each side of the developing forebrain in the neural folds - this is the optic grooves. The optic placode has begun to develop, which is seen by a small thickening of the surface ectoderm lateral to the hindbrain.
|-
| Stage 11 (24 days) || Optic vesicle begins to form from the optic groove. Otic pit has formed.
|-
| Stage 12 (26 days) || The optic vesicles have extended from the forbrain to the surface ectoderm. The optic vesicle now lies close to the surface ectoderm.
|-
| Stage 13 (28 days) || The optic vesicle interacts with the surface ectoderm and will induce this ectoderm to form the lens placode, which is the precursor of the lens.
|-
| Stage 14 (32 days) || The lens placode is indented by the lens pit and may be cup-shaped.
|-
| Stage 15 (33 days) || The lens pit will close and form a circle that separates from the surface ectoderm and becomes the lens vesicle. The lens vesicle and optic cub lie close to the surface ectoderm, which creates a slight elevation in the region of the eye.
|-
| Stage 16 (37 days ) || First indication of the development of the eyelids.
|-
| Stage 17 (41 days) || Retinal pigment is visible. The eyes are still laterally places, but starts to take a more anterior position. The lower eyelid fold has begun to form.
|-
| Stage 18 (44 days) || Mesenchyme invades the region between the lens epithelium and the surface ectoderm. The eyes has shifted to more anterior position. The groove above and below the eyes are deeper, but have not joined yet. Eyelid folds develop.
|-
| Stage 19 (48 days) || The upper and the lower eyelids now meet at the outer canthus.
|-
| Stage 20 (51 days) || The lens cavity is lost. The upper and lower lids meet laterally and medially. The eyelids now partly cover the eye.
|-
| Stage 21 (52 days) ||
|-
| Stage 22 (54 days) ||
|-
| Stage 23 (57 days) || The face is beginning to look human.
|-
|}

=== Embryonic Contributions ===

The eyes are derived from four sources:

{| class="wikitable"
! style="background:#f4a941" | Embryonic contributions
! style="background:#f4a941" | Eye component
|-
| Neuroectoderm of the forebrain || Retina, Posterior layers of the iris, The optic nerve
|-
| Surface ectoderm of the head || The lens of the eye, The corneal epithelium
|-
| Mesoderm between the neuroectoderm and the surface ectoderm || The fibrous and vascular coats of the eye
|-
| Neural crest cells || Choroid, Sclera, Corneal endothelium
|}

=== Short overview ===

[[File:DevelopmentEye-PMC43029243.jpg|400px|thumb|right|'''Figure 1.''' Stages of lens formation in mouse embryos]]

The eye starts to develop at 22 days. The optic grooves (sulci) appears in the neural folds at the cranial end of the embryo. When the neural fold fuse to form the forebrain, the optic grooves will form optic vesicles. The optic vesicles are continuous cavities from the cavity of the forebrain and project from the wall of the forebrain and into the mesenchyme. The optic vesicle extends from the diencephalon and will come in contact with the surface ectoderm of the head. This induces the formation of a lens placode. The surface ectoderm near the optic vesicles will thicken and form the lens placodes. The lens placodes will sink into the surface ectoderm and form lens pits. The edges of the lens pits will travel towards each other and fuse to form round lens vesicles, which will later lose connection with the surface ectoderm. The optic vesicles do also keep developing - they will form double-walled optic cups which are connected to the brain by the optic stalk. The two layers of the optic cup will differentiate in different directions. The cells of the outer layer will produce melanin pigment and later become the pigmented retina. The cells of the inner layer of the optic cup will proliferate fast and develop glia, ganglion cells, interneurons and light-sensitive photoreceptor neurons. These cells are in the neural retina. The ganglion cells of the retina are neurons that send signal to the brain. The axons of the ganglion cells of the neural retina will grow in the wall of the optic stalk. The cavity in the optic nerve will start disappearing, and instead, the axons of the ganglion cells will form the '''optic nerve'''.
The optic stalk is now the optic nerve <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>

The optic cups will fold inwards around the lens while the lens vesicles have grown inwards so they have fully lost their connection with the surface ectoderm, which locates them in the cavities of the optic cups. The retinal fissures (linear grooves) will develop and cover the ventral surface of the optic cups and down to the optic stalk. The retinal fissures contain vascular mesenchyme and hyaloid blood vessels will develop here. The hyaloid artery supplies the structures in the eye with blood and the hyaloid vein will return the blood from these structures.

'''Formation of the optic vesicle'''

It is a specific area of the neural ectoderm that will become the optic vesicle - this happens because of a group of transcription factors - Six3, Pax6, and Rx1. These transcription factors are expressed in the most anterior tip of the neural plate. This area will split into bilateral regions and form the optic vesicles. The Pax6 protein has shown to be especially important for the development of the lens and retina. This protein is important for photoreceptive cells in all phyla. Pax 6 is also present in the murine forebrain, hindbrain, and nasal placodes, but the eyes are most sensitive its absence <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

The sonic hedgehog gene is important for the separation of the single eye field into two fields. If this gene is inhibited, the eye field will not split which will result in cyclopia, a single eye in the center of the face <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

== Development of the eye components ==

=== Lens ===

Human lens induction occurs at around 28 days and is completed around day 56. The surface ectoderm will thicken near the optic vesicle and create the lens placode and later form the lens vesicle <ref><pubmed>20171212 </pubmed></ref>. Lens cells come from ectoderm and differentiate into either lens fibers or the lens epithelium. The anterior monolayer of epithelial cells of the lens will create the lens epithelium, which makes the sheet of cuboidal epithelium covering the anterior surface of the lens. The posterior lens vesicle cells will produce the linear primary fibre cells aligned parallel to the optic axis. These fibres will create the lens mass and form the embryonic lens nucleus. The lens epithelial cells will keep proliferating and produce new cells which generate a secondary lens fiber cells. This rows of cell will form the outer shells and keep the lens growing throughout life. This makes the eye lens unique - it will have an addition of new cells inside the surrounding capsule all the time <ref><pubmed>25406393</pubmed></ref>.

=== Retina ===
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=== Ciliary Body ===

The ciliary body is a muscular and secretory tissue and is located directly behind the lens. The ciliary body forms part of the anterior segment of the eye and is an important regulator of eye physiology and the vision. The ciliary body produces the aqueous fluid which fills the eyes and nourishes the lens and cornea - this aqueous fluid function to keep the eye in a pressurized and inflated state, which is important the vision.The ciliary body also synthesizes collagenIX and tenasin-C <ref><pubmed>17275804</pubmed></ref>.

The ciliary body extends from the iris root (anteriorly) to the ora serrata (posteriorly). It consist of ciliary muscles and ciliary processes. Each ciliary process (fold) is covered by a double-layered secretory epithelium; the outer pigmented and the inner unpigmented (closes to the lens). The epithelial layers of the ciliary body comes from the retina of the optic cup. We see two different ciliary body epithelium: the inner non-pigmented ciliary epithelium which is connected with the neural retina and the outer pigmented ciliary epithelium which is connected with the retinal pigmented epithelium. The epithelium of the iris is the further anterior extension. The epithelial layers are associated with a stroma containing the ciliary muscle. The ciliary muscle is complex, but can be divided into three portions; anterior, posterior and internal <ref><pubmed>12127103</pubmed></ref>.

In the chick eye development, we see the mesenchyme grow together on the margin of the optic cup and will form the stroma of the ciliary body and the iris, which is located more anteriorly. It is unknown how if the lens has a role in inducing the secretory ciliary body epithelium and the muscular iris epithelium <ref><pubmed>17275804</pubmed></ref>.

=== Iris ===

The Iris develops at the end of the third month of development. The iris is a thin layer and derives from the anterior rim of the optic cup. In the anterior of the eye, the optic epithelium is nonneural and matures as ciliary body and iris epithelia.

=== Cornea ===

http://www.sciencedirect.com/science/article/pii/S1877117315000642

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1298807/pdf/taos00013-0203.pdf

=== Aqueous Chambers ===
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=== Choroid and Sclera ===
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<ref><pubmed>23528534</pubmed></ref>

=== Eyelids ===

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=== Lacrimal Glands ===

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=== Extraocular muscles ===
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<pubmed>26410132</pubmed>
<pubmed>23071378</pubmed>

We could talk briefly in this sections about the causes of short/long-sightedness and common causes of blindness at a developmental level - z3416557

== Congenital Anomalies ==
We could talk briefly in this sections about the causes of short/long-sightedness and common causes of blindness at a developmental level - z3416557

Although quite rare, abnormalities can occur during the embryonic development that causes serious effects to the features of the eyes, its function as well as the further normal development after birth. These anomalies can occur unilaterally or bilaterally and it is also common for most reported cases to have more than one type of eye abnormalities at a time. Thus, the estimated prevalence statistics listed in the table can overlap.

{| class="wikitable"
! style="background:#f4a941" | Congenital Anomalies
! style="background:#f4a941" | Description
! style="background:#f4a941" | Epidemiology
|-
| Anopthalmia || The absence of the eyes.
| rowspan="2" | Prevalence: Anophthalmia-Microphthalmia Syndrome was estimated to be 5.3 per 100 000 cases <ref name="Orphanet Report Series - Rare Diseases Collection">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: http://www.orpha.net</ref>
|-
| Microphtalmia || Abnormal reduction in size of the eyeballs.
|-
| Coloboma || A condition where parts of the eye is missing and failed to develop normally.
| Prevalence: Occular coloboma was estimated to be 8.0 per 100 000 cases <ref name="Orphanet Report Series - Rare Diseases Collection">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: http://www.orpha.net</ref>
|-
| Aniridia || Complete or partial absence of the iris.
| Prevalence: Estimated to be 1.5 per 100 000 cases <ref name="Orphanet Report Series - Rare Diseases Collection">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: http://www.orpha.net</ref>
|-
| Optic Nerve Hypoplasia || A condition where the optic nerves are underdeveloped.
| Prevalence: Reported to be the most common abnormality <ref name="The Optic Nerve Hypoplasia">Ryabets-Lienhard, A., Stewart, C., Borchert, M., & Geffner, M. E. (2016). The Optic Nerve Hypoplasia Spectrum - Review of the Literature and Clinical Guidelines. ''Advances in Pediatrics, 63'', 127-146. doi: 10.1016/j.yapd.2016.04.009 </ref>
*10.9 per 100 000 in United Kingdom
*17.3 per 100 000 cases in Sweden.
*6.3% of cases was reported in New Zealand
|-
|}

[[File:Anophthalmia.jpeg|150px|thumb|left|'''Figure 2.''' Anopthalmia birth defect]]
[[File:Microphthalmia-500px.jpg|150px|thumb|centre|'''Figure 3.''' Microphthalmia birth defect]]

==Glossary==

==References==

<references/>

==External links==

z5075309 - <pubmed>26956898</pubmed>

2017 Group Project 4

2017-10-05T03:58:52Z

Z3416557:

{{ANAT2341Project2017header}}

= Eye Development =
[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 16:09, 14 September 2017 (AEST) OK Feedback
* Timelines
* Embryonic contributions from germ layers and neural crest
* Cellular components
* Current research areas
* Get rid of the bold formatting for sub-headings.
* Animal models compared to human development
* Central neural pathway

== Anatomy of the Adult Eye ==

The eye is a complex sensory structure which allows a variety of species to intake and process visual information from the world around us.

To discuss the key anatomical components of the eye, we will break down the eye in parts<ref>Chen, J., 2011. Handbook of Visual Display Technology. Springer Berlin Heidelberg. Chapter 2.1</ref>:

'''Supporting Structures (Orbit, Extraoccular Muscles, Lacrimal Gland, Eyelid)'''
[[File:22292144 10208413540209536 722417340 o.jpg|250px|thumb|right]]
The orbit of the eye consists of a framework of bones and connective tissue which provide structural support and protection to the sensitive human eye. 7 bones contribute to the orbit of the eye: frontal, lacrimal, sphenoid, zygomtatic, ethmoid, maxilary, palatine. Several openings exist in the orbital structure, 2 key fissures are the superior orbital fissure and inferior orbital fissure and the posterior optic canal. These openings allow crainial nerves passageway.

A set of 6 extraoccular muscles allow for a strong voluntary control of the movement of the eye. These muscles include superior recuts, inferior rectus, lateral rectus, medial rectus, inferior oblique, superior oblique muscles. These muscles are some of the smallest in the human body and are designed to produce fast, controlled motion to focus on an object of interest.

The eyelid is the anterior covering of the eye, consisting of a thin fold of skin. It is controlled by the levitator palpabrae superioris muscle. Superio-laterally to the eyelid is the lacrimal gland, which serves to create a film of tear, an important component to keeping the anterior surface of the eye moist. The eyelid assists in this process by opening and closing, or blinking, which spreads the tear film across the surface of the eye. Tear film and debris caught in the tear film are excreted through the lacrimal duct which is located on the infero-medial surface of the eyelid.
[[File:22251179_10208414266827701_870733039_o.jpg|250px|thumb|right]]

'''Layers of the Eyeball (Sclera, Choroid, Retina)'''

The superficial layers of the eyeball is the sclera, a thick fibrous layer which becomes thicker as it extends posteriorly. The sclera is the visible as the white part of our eye. It's function is to provide structural stability to the eye and serves as attachment for some extraoccular insertions. Deep to the sclera is the choroid, a vascular network which provides nourishment to the layers of the eyeball and plays a large role in the growth of the eye. Deep to the choroid is the retina, a network of nerve fibers which transmit visual information. The retina contains 2 types of photoreceptors which convert visible light into nerve impulses. Rods work best in low light environments while cones work best in high light enthronements and detect colour and sharp detail.<ref>Curcio CA, Hendrickson AE. Organization and development of the primate photoreceptor mosaic. Prog Ret Ret. 1991;10:89–120.</ref>: The retina does not extend to the anterior part of the eyeball, unlike the sclera and choroid layers.

'''Anterior structure (Lens, Cornea, Pupil, Iris, Ciliary Body, Conjunctiva Anterior Chamber)'''

The most anterior component of the eyeball is the cornea, which is a multilayered avascular transparent structure who's major function to the refract light to assist image formation (contributes about 75% of total refraction). Continuous with cornea superiorly and inferiorly is the conjunctiva. Deep to the cornera is the iris, or the coloured ring visible in the eye. The iris consists of 2 muscles which act to enhance and diminish the size of the pupil, a hole in the middle of the iris allowing light to enter the eye. Deep to the pupil and iris is the lens, which is a transparent structure which contributes the other 25% of the eye's refractive power. The lens changes shape through accomodation controlled by the ciliary body muscles. The ciliary body is the anterior extension of the choroid. The function of the lens is to focus images by changing refractive power based on the position and depth of focal objects. In between the anterior surface of the lens and posterior surface of the cornea is the anterior chamber. This chamber is filled with aqueous humor supplied by the ciliary body, who's function is to provide nutrients to ocular structures and maintain intraocular pressure.
[[File:22251314_10208414283908128_862494115_o.jpg|250px|thumb|right]]

'''Posterior structure (Optic Nerve, Optic Disc, Macula, Fovea, Posterior Chamber)'''

In the posterior section of the retina is the macula, a central spot in which a high concentration of cone photoreceptors are found. The direct centre of the macula is called the fovea which contains solely cone photoreceptors. The fovea is only part of the eye which can conduct 'perfect' 20/20 vision. It has a high workload and hence a strong vascular supporting structure<ref>Hendrickson AE, Youdelis C. The morphological development of the human fovea. Ophthalmology. 1984;91:603–612.</ref>:. The most posterior part of the eye is the optic nerve (along with the central retinal artery and central retinal vein), which is responsible for transporting nerve impulses to the cerebral cortex for processing. The opening of the optic nerve is called the optic disc, which contains no photoreceptors and is a blind spot of the eye. Between the posterior surface of the lens, the retina and the optic disc is the posterior chamber. The posterior chamber contains a vitreous humour, a jelly like substance with a high viscosity.

==Overview of eye development==

=== Timeline of embryonic development ===

{| class="wikitable"
! style="background:#f4a941" | WEEK
! style="background:#f4a941" | DEVELOPMENT
|-
| 3-4 || Eye fields, Optic vesicles
|-
| 5-6 || Optic Cup, Lens Vesicle, Choroid Fissure, Hyaloid Artery
|-
| 7-8 || Cornea, Anterior Chamber, Pupillary Membrane, Lens, Retina
|-
| 8-10 || Eyelids
|-
| 9-15 || Iris, Ciliary Body
|}

=== Carnegie Stages ===

Carnegie Stages is a system of 23 stages used to describe developmental events of the vertebrate embryo. At stage 10 we see early signs related to eye development <ref><pubmed>7364662</pubmed></ref>.

{| class="wikitable"
! style="background:#f4a941" | STAGE
! style="background:#f4a941" | EVENTS
|-
| Stage 10 (22 days) || The optic primordium has developed. Two small grooves develop on each side of the developing forebrain in the neural folds - this is the optic grooves. The optic placode has begun to develop, which is seen by a small thickening of the surface ectoderm lateral to the hindbrain.
|-
| Stage 11 (24 days) || Optic vesicle begins to form from the optic groove. Otic pit has formed.
|-
| Stage 12 (26 days) || The optic vesicles have extended from the forbrain to the surface ectoderm. The optic vesicle now lies close to the surface ectoderm.
|-
| Stage 13 (28 days) || The optic vesicle interacts with the surface ectoderm and will induce this ectoderm to form the lens placode, which is the precursor of the lens.
|-
| Stage 14 (32 days) || The lens placode is indented by the lens pit and may be cup-shaped.
|-
| Stage 15 (33 days) || The lens pit will close and form a circle that separates from the surface ectoderm and becomes the lens vesicle. The lens vesicle and optic cub lie close to the surface ectoderm, which creates a slight elevation in the region of the eye.
|-
| Stage 16 (37 days ) || First indication of the development of the eyelids.
|-
| Stage 17 (41 days) || Retinal pigment is visible. The eyes are still laterally places, but starts to take a more anterior position. The lower eyelid fold has begun to form.
|-
| Stage 18 (44 days) || Mesenchyme invades the region between the lens epithelium and the surface ectoderm. The eyes has shifted to more anterior position. The groove above and below the eyes are deeper, but have not joined yet. Eyelid folds develop.
|-
| Stage 19 (48 days) || The upper and the lower eyelids now meet at the outer canthus.
|-
| Stage 20 (51 days) || The lens cavity is lost. The upper and lower lids meet laterally and medially. The eyelids now partly cover the eye.
|-
| Stage 21 (52 days) ||
|-
| Stage 22 (54 days) ||
|-
| Stage 23 (57 days) || The face is beginning to look human.
|-
|}

=== Embryonic Contributions ===

The eyes are derived from four sources:

{| class="wikitable"
! style="background:#f4a941" | Embryonic contributions
! style="background:#f4a941" | Eye component
|-
| Neuroectoderm of the forebrain || Retina, Posterior layers of the iris, The optic nerve
|-
| Surface ectoderm of the head || The lens of the eye, The corneal epithelium
|-
| Mesoderm between the neuroectoderm and the surface ectoderm || The fibrous and vascular coats of the eye
|-
| Neural crest cells || Choroid, Sclera, Corneal endothelium
|}

=== Short overview ===

[[File:DevelopmentEye-PMC43029243.jpg|400px|thumb|right|'''Figure 1.''' Stages of lens formation in mouse embryos]]

The eye starts to develop at 22 days. The optic grooves (sulci) appears in the neural folds at the cranial end of the embryo. When the neural fold fuse to form the forebrain, the optic grooves will form optic vesicles. The optic vesicles are continuous cavities from the cavity of the forebrain and project from the wall of the forebrain and into the mesenchyme. The optic vesicle extends from the diencephalon and will come in contact with the surface ectoderm of the head. This induces the formation of a lens placode. The surface ectoderm near the optic vesicles will thicken and form the lens placodes. The lens placodes will sink into the surface ectoderm and form lens pits. The edges of the lens pits will travel towards each other and fuse to form round lens vesicles, which will later lose connection with the surface ectoderm. The optic vesicles do also keep developing - they will form double-walled optic cups which are connected to the brain by the optic stalk. The two layers of the optic cup will differentiate in different directions. The cells of the outer layer will produce melanin pigment and later become the pigmented retina. The cells of the inner layer of the optic cup will proliferate fast and develop glia, ganglion cells, interneurons and light-sensitive photoreceptor neurons. These cells are in the neural retina. The ganglion cells of the retina are neurons that send signal to the brain. The axons of the ganglion cells of the neural retina will grow in the wall of the optic stalk. The cavity in the optic nerve will start disappearing, and instead, the axons of the ganglion cells will form the '''optic nerve'''.
The optic stalk is now the optic nerve <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>

The optic cups will fold inwards around the lens while the lens vesicles have grown inwards so they have fully lost their connection with the surface ectoderm, which locates them in the cavities of the optic cups. The retinal fissures (linear grooves) will develop and cover the ventral surface of the optic cups and down to the optic stalk. The retinal fissures contain vascular mesenchyme and hyaloid blood vessels will develop here. The hyaloid artery supplies the structures in the eye with blood and the hyaloid vein will return the blood from these structures.

'''Formation of the optic vesicle'''

It is a specific area of the neural ectoderm that will become the optic vesicle - this happens because of a group of transcription factors - Six3, Pax6, and Rx1. These transcription factors are expressed in the most anterior tip of the neural plate. This area will split into bilateral regions and form the optic vesicles. The Pax6 protein has shown to be especially important for the development of the lens and retina. This protein is important for photoreceptive cells in all phyla. Pax 6 is also present in the murine forebrain, hindbrain, and nasal placodes, but the eyes are most sensitive its absence <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

The sonic hedgehog gene is important for the separation of the single eye field into two fields. If this gene is inhibited, the eye field will not split which will result in cyclopia, a single eye in the center of the face <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

== Development of the eye components ==

=== Lens ===

Human lens induction occurs at around 28 days and is completed around day 56. The surface ectoderm will thicken near the optic vesicle and create the lens placode and later form the lens vesicle <ref><pubmed>20171212 </pubmed></ref>. Lens cells come from ectoderm and differentiate into either lens fibers or the lens epithelium. The anterior monolayer of epithelial cells of the lens will create the lens epithelium, which makes the sheet of cuboidal epithelium covering the anterior surface of the lens. The posterior lens vesicle cells will produce the linear primary fibre cells aligned parallel to the optic axis. These fibres will create the lens mass and form the embryonic lens nucleus. The lens epithelial cells will keep proliferating and produce new cells which generate a secondary lens fiber cells. This rows of cell will form the outer shells and keep the lens growing throughout life. This makes the eye lens unique - it will have an addition of new cells inside the surrounding capsule all the time <ref><pubmed>25406393</pubmed></ref>.

=== Retina ===
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=== Ciliary Body ===

The ciliary body is a muscular and secretory tissue and is located directly behind the lens. The ciliary body forms part of the anterior segment of the eye and is an important regulator of eye physiology and the vision. The ciliary body produces the aqueous fluid which fills the eyes and nourishes the lens and cornea - this aqueous fluid function to keep the eye in a pressurized and inflated state, which is important the vision.The ciliary body also synthesizes collagenIX and tenasin-C <ref><pubmed>17275804</pubmed></ref>.

The ciliary body extends from the iris root (anteriorly) to the ora serrata (posteriorly). It consist of ciliary muscles and ciliary processes. Each ciliary process (fold) is covered by a double-layered secretory epithelium; the outer pigmented and the inner unpigmented (closes to the lens). The epithelial layers of the ciliary body comes from the retina of the optic cup. We see two different ciliary body epithelium: the inner non-pigmented ciliary epithelium which is connected with the neural retina and the outer pigmented ciliary epithelium which is connected with the retinal pigmented epithelium. The epithelium of the iris is the further anterior extension. The epithelial layers are associated with a stroma containing the ciliary muscle. The ciliary muscle is complex, but can be divided into three portions; anterior, posterior and internal <ref><pubmed>12127103</pubmed></ref>.

In the chick eye development, we see the mesenchyme grow together on the margin of the optic cup and will form the stroma of the ciliary body and the iris, which is located more anteriorly. It is unknown how if the lens has a role in inducing the secretory ciliary body epithelium and the muscular iris epithelium <ref><pubmed>17275804</pubmed></ref>.

=== Iris ===

The Iris develops at the end of the third month of development. The iris is a thin layer and derives from the anterior rim of the optic cup. In the anterior of the eye, the optic epithelium is nonneural and matures as ciliary body and iris epithelia.

=== Cornea ===

http://www.sciencedirect.com/science/article/pii/S1877117315000642

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1298807/pdf/taos00013-0203.pdf

=== Aqueous Chambers ===
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=== Choroid and Sclera ===
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<ref><pubmed>23528534</pubmed></ref>

=== Eyelids ===

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=== Lacrimal Glands ===

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=== Extraocular muscles ===
5075778

<pubmed>26410132</pubmed>
<pubmed>23071378</pubmed>

We could talk briefly in this sections about the causes of short/long-sightedness and common causes of blindness at a developmental level - z3416557

== Congenital Anomalies ==
We could talk briefly in this sections about the causes of short/long-sightedness and common causes of blindness at a developmental level - z3416557

Although quite rare, abnormalities can occur during the embryonic development that causes serious effects to the features of the eyes, its function as well as the further normal development after birth. These anomalies can occur unilaterally or bilaterally and it is also common for most reported cases to have more than one type of eye abnormalities at a time. Thus, the estimated prevalence statistics listed in the table can overlap.

{| class="wikitable"
! style="background:#f4a941" | Congenital Anomalies
! style="background:#f4a941" | Description
! style="background:#f4a941" | Epidemiology
|-
| Anopthalmia || The absence of the eyes.
| rowspan="2" | Prevalence: Anophthalmia-Microphthalmia Syndrome was estimated to be 5.3 per 100 000 cases <ref name="Orphanet Report Series - Rare Diseases Collection">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: http://www.orpha.net</ref>
|-
| Microphtalmia || Abnormal reduction in size of the eyeballs.
|-
| Coloboma || A condition where parts of the eye is missing and failed to develop normally.
| Prevalence: Occular coloboma was estimated to be 8.0 per 100 000 cases <ref name="Orphanet Report Series - Rare Diseases Collection">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: http://www.orpha.net</ref>
|-
| Aniridia || Complete or partial absence of the iris.
| Prevalence: Estimated to be 1.5 per 100 000 cases <ref name="Orphanet Report Series - Rare Diseases Collection">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: http://www.orpha.net</ref>
|-
| Optic Nerve Hypoplasia || A condition where the optic nerves are underdeveloped.
| Prevalence: Reported to be the most common abnormality <ref name="The Optic Nerve Hypoplasia">Ryabets-Lienhard, A., Stewart, C., Borchert, M., & Geffner, M. E. (2016). The Optic Nerve Hypoplasia Spectrum - Review of the Literature and Clinical Guidelines. ''Advances in Pediatrics, 63'', 127-146. doi: 10.1016/j.yapd.2016.04.009 </ref>
*10.9 per 100 000 in United Kingdom
*17.3 per 100 000 cases in Sweden.
*6.3% of cases was reported in New Zealand
|-
|}

[[File:Anophthalmia.jpeg|150px|thumb|left|'''Figure 2.''' Anopthalmia birth defect]]
[[File:Microphthalmia-500px.jpg|150px|thumb|centre|'''Figure 3.''' Microphthalmia birth defect]]

==Glossary==

==References==

<references/>

==External links==

z5075309 - <pubmed>26956898</pubmed>

2017 Group Project 4

2017-10-05T03:57:23Z

Z3416557:

{{ANAT2341Project2017header}}

= Eye Development =
[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 16:09, 14 September 2017 (AEST) OK Feedback
* Timelines
* Embryonic contributions from germ layers and neural crest
* Cellular components
* Current research areas
* Get rid of the bold formatting for sub-headings.
* Animal models compared to human development
* Central neural pathway

== Anatomy of the Adult Eye ==

The eye is a complex sensory structure which allows a variety of species to intake and process visual information from the world around us.

To discuss the key anatomical components of the eye, we will break down the eye in parts<ref>Chen, J., 2011. Handbook of Visual Display Technology. Springer Berlin Heidelberg. Chapter 2.1</ref>:

'''Supporting Structures (Orbit, Extraoccular Muscles, Lacrimal Gland, Eyelid)'''
[[File:22292144 10208413540209536 722417340 o.jpg|250px|thumb|right]]
The orbit of the eye consists of a framework of bones and connective tissue which provide structural support and protection to the sensitive human eye. 7 bones contribute to the orbit of the eye: frontal, lacrimal, sphenoid, zygomtatic, ethmoid, maxilary, palatine. Several openings exist in the orbital structure, 2 key fissures are the superior orbital fissure and inferior orbital fissure and the posterior optic canal. These openings allow crainial nerves passageway.

A set of 6 extraoccular muscles allow for a strong voluntary control of the movement of the eye. These muscles include superior recuts, inferior rectus, lateral rectus, medial rectus, inferior oblique, superior oblique muscles. These muscles are some of the smallest in the human body and are designed to produce fast, controlled motion to focus on an object of interest.

The eyelid is the anterior covering of the eye, consisting of a thin fold of skin. It is controlled by the levitator palpabrae superioris muscle. Superio-laterally to the eyelid is the lacrimal gland, which serves to create a film of tear, an important component to keeping the anterior surface of the eye moist. The eyelid assists in this process by opening and closing, or blinking, which spreads the tear film across the surface of the eye. Tear film and debris caught in the tear film are excreted through the lacrimal duct which is located on the infero-medial surface of the eyelid.
[[File:22251179_10208414266827701_870733039_o.jpg|250px|thumb|right]]

'''Layers of the Eyeball (Sclera, Choroid, Retina)'''

The superficial layers of the eyeball is the sclera, a thick fibrous layer which becomes thicker as it extends posteriorly. The sclera is the visible as the white part of our eye. It's function is to provide structural stability to the eye and serves as attachment for some extraoccular insertions. Deep to the sclera is the choroid, a vascular network which provides nourishment to the layers of the eyeball and plays a large role in the growth of the eye. Deep to the choroid is the retina, a network of nerve fibers which transmit visual information. The retina contains 2 types of photoreceptors which convert visible light into nerve impulses. Rods work best in low light environments while cones work best in high light enthronements and detect colour and sharp detail.<ref>Curcio CA, Hendrickson AE. Organization and development of the primate photoreceptor mosaic. Prog Ret Ret. 1991;10:89–120.</ref>: The retina does not extend to the anterior part of the eyeball, unlike the sclera and choroid layers.

'''Anterior structure (Lens, Cornea, Pupil, Iris, Ciliary Body, Conjunctiva Anterior Chamber)'''

The most anterior component of the eyeball is the cornea, which is a multilayered avascular transparent structure who's major function to the refract light to assist image formation (contributes about 75% of total refraction). Continuous with cornea superiorly and inferiorly is the conjunctiva. Deep to the cornera is the iris, or the coloured ring visible in the eye. The iris consists of 2 muscles which act to enhance and diminish the size of the pupil, a hole in the middle of the iris allowing light to enter the eye. Deep to the pupil and iris is the lens, which is a transparent structure which contributes the other 25% of the eye's refractive power. The lens changes shape through accomodation controlled by the ciliary body muscles. The ciliary body is the anterior extension of the choroid. The function of the lens is to focus images by changing refractive power based on the position and depth of focal objects. In between the anterior surface of the lens and posterior surface of the cornea is the anterior chamber. This chamber is filled with aqueous humor supplied by the ciliary body, who's function is to provide nutrients to ocular structures and maintain intraocular pressure.
[[File:22251314_10208414283908128_862494115_o.jpg|250px|thumb|right]]

'''Posterior structure (Optic Nerve, Optic Disc, Macula, Fovea, Posterior Chamber)'''

In the posterior section of the retina is the macula, a central spot in which a high concentration of cone photoreceptors are found. The direct centre of the macula is called the fovea which contains solely cone photoreceptors. The fovea is only part of the eye which can conduct 'perfect' 20/20 vision. It has a high workload and hence a strong vascular supporting structure. The most posterior part of the eye is the optic nerve (along with the central retinal artery and central retinal vein), which is responsible for transporting nerve impulses to the cerebral cortex for processing. The opening of the optic nerve is called the optic disc, which contains no photoreceptors and is a blind spot of the eye. Between the posterior surface of the lens, the retina and the optic disc is the posterior chamber. The posterior chamber contains a vitreous humour, a jelly like substance with a high viscosity.

==Overview of eye development==

=== Timeline of embryonic development ===

{| class="wikitable"
! style="background:#f4a941" | WEEK
! style="background:#f4a941" | DEVELOPMENT
|-
| 3-4 || Eye fields, Optic vesicles
|-
| 5-6 || Optic Cup, Lens Vesicle, Choroid Fissure, Hyaloid Artery
|-
| 7-8 || Cornea, Anterior Chamber, Pupillary Membrane, Lens, Retina
|-
| 8-10 || Eyelids
|-
| 9-15 || Iris, Ciliary Body
|}

=== Carnegie Stages ===

Carnegie Stages is a system of 23 stages used to describe developmental events of the vertebrate embryo. At stage 10 we see early signs related to eye development <ref><pubmed>7364662</pubmed></ref>.

{| class="wikitable"
! style="background:#f4a941" | STAGE
! style="background:#f4a941" | EVENTS
|-
| Stage 10 (22 days) || The optic primordium has developed. Two small grooves develop on each side of the developing forebrain in the neural folds - this is the optic grooves. The optic placode has begun to develop, which is seen by a small thickening of the surface ectoderm lateral to the hindbrain.
|-
| Stage 11 (24 days) || Optic vesicle begins to form from the optic groove. Otic pit has formed.
|-
| Stage 12 (26 days) || The optic vesicles have extended from the forbrain to the surface ectoderm. The optic vesicle now lies close to the surface ectoderm.
|-
| Stage 13 (28 days) || The optic vesicle interacts with the surface ectoderm and will induce this ectoderm to form the lens placode, which is the precursor of the lens.
|-
| Stage 14 (32 days) || The lens placode is indented by the lens pit and may be cup-shaped.
|-
| Stage 15 (33 days) || The lens pit will close and form a circle that separates from the surface ectoderm and becomes the lens vesicle. The lens vesicle and optic cub lie close to the surface ectoderm, which creates a slight elevation in the region of the eye.
|-
| Stage 16 (37 days ) || First indication of the development of the eyelids.
|-
| Stage 17 (41 days) || Retinal pigment is visible. The eyes are still laterally places, but starts to take a more anterior position. The lower eyelid fold has begun to form.
|-
| Stage 18 (44 days) || Mesenchyme invades the region between the lens epithelium and the surface ectoderm. The eyes has shifted to more anterior position. The groove above and below the eyes are deeper, but have not joined yet. Eyelid folds develop.
|-
| Stage 19 (48 days) || The upper and the lower eyelids now meet at the outer canthus.
|-
| Stage 20 (51 days) || The lens cavity is lost. The upper and lower lids meet laterally and medially. The eyelids now partly cover the eye.
|-
| Stage 21 (52 days) ||
|-
| Stage 22 (54 days) ||
|-
| Stage 23 (57 days) || The face is beginning to look human.
|-
|}

=== Embryonic Contributions ===

The eyes are derived from four sources:

{| class="wikitable"
! style="background:#f4a941" | Embryonic contributions
! style="background:#f4a941" | Eye component
|-
| Neuroectoderm of the forebrain || Retina, Posterior layers of the iris, The optic nerve
|-
| Surface ectoderm of the head || The lens of the eye, The corneal epithelium
|-
| Mesoderm between the neuroectoderm and the surface ectoderm || The fibrous and vascular coats of the eye
|-
| Neural crest cells || Choroid, Sclera, Corneal endothelium
|}

=== Short overview ===

[[File:DevelopmentEye-PMC43029243.jpg|400px|thumb|right|'''Figure 1.''' Stages of lens formation in mouse embryos]]

The eye starts to develop at 22 days. The optic grooves (sulci) appears in the neural folds at the cranial end of the embryo. When the neural fold fuse to form the forebrain, the optic grooves will form optic vesicles. The optic vesicles are continuous cavities from the cavity of the forebrain and project from the wall of the forebrain and into the mesenchyme. The optic vesicle extends from the diencephalon and will come in contact with the surface ectoderm of the head. This induces the formation of a lens placode. The surface ectoderm near the optic vesicles will thicken and form the lens placodes. The lens placodes will sink into the surface ectoderm and form lens pits. The edges of the lens pits will travel towards each other and fuse to form round lens vesicles, which will later lose connection with the surface ectoderm. The optic vesicles do also keep developing - they will form double-walled optic cups which are connected to the brain by the optic stalk. The two layers of the optic cup will differentiate in different directions. The cells of the outer layer will produce melanin pigment and later become the pigmented retina. The cells of the inner layer of the optic cup will proliferate fast and develop glia, ganglion cells, interneurons and light-sensitive photoreceptor neurons. These cells are in the neural retina. The ganglion cells of the retina are neurons that send signal to the brain. The axons of the ganglion cells of the neural retina will grow in the wall of the optic stalk. The cavity in the optic nerve will start disappearing, and instead, the axons of the ganglion cells will form the '''optic nerve'''.
The optic stalk is now the optic nerve <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>

The optic cups will fold inwards around the lens while the lens vesicles have grown inwards so they have fully lost their connection with the surface ectoderm, which locates them in the cavities of the optic cups. The retinal fissures (linear grooves) will develop and cover the ventral surface of the optic cups and down to the optic stalk. The retinal fissures contain vascular mesenchyme and hyaloid blood vessels will develop here. The hyaloid artery supplies the structures in the eye with blood and the hyaloid vein will return the blood from these structures.

'''Formation of the optic vesicle'''

It is a specific area of the neural ectoderm that will become the optic vesicle - this happens because of a group of transcription factors - Six3, Pax6, and Rx1. These transcription factors are expressed in the most anterior tip of the neural plate. This area will split into bilateral regions and form the optic vesicles. The Pax6 protein has shown to be especially important for the development of the lens and retina. This protein is important for photoreceptive cells in all phyla. Pax 6 is also present in the murine forebrain, hindbrain, and nasal placodes, but the eyes are most sensitive its absence <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

The sonic hedgehog gene is important for the separation of the single eye field into two fields. If this gene is inhibited, the eye field will not split which will result in cyclopia, a single eye in the center of the face <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

== Development of the eye components ==

=== Lens ===

Human lens induction occurs at around 28 days and is completed around day 56. The surface ectoderm will thicken near the optic vesicle and create the lens placode and later form the lens vesicle <ref><pubmed>20171212 </pubmed></ref>. Lens cells come from ectoderm and differentiate into either lens fibers or the lens epithelium. The anterior monolayer of epithelial cells of the lens will create the lens epithelium, which makes the sheet of cuboidal epithelium covering the anterior surface of the lens. The posterior lens vesicle cells will produce the linear primary fibre cells aligned parallel to the optic axis. These fibres will create the lens mass and form the embryonic lens nucleus. The lens epithelial cells will keep proliferating and produce new cells which generate a secondary lens fiber cells. This rows of cell will form the outer shells and keep the lens growing throughout life. This makes the eye lens unique - it will have an addition of new cells inside the surrounding capsule all the time <ref><pubmed>25406393</pubmed></ref>.

=== Retina ===
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=== Ciliary Body ===

The ciliary body is a muscular and secretory tissue and is located directly behind the lens. The ciliary body forms part of the anterior segment of the eye and is an important regulator of eye physiology and the vision. The ciliary body produces the aqueous fluid which fills the eyes and nourishes the lens and cornea - this aqueous fluid function to keep the eye in a pressurized and inflated state, which is important the vision.The ciliary body also synthesizes collagenIX and tenasin-C <ref><pubmed>17275804</pubmed></ref>.

The ciliary body extends from the iris root (anteriorly) to the ora serrata (posteriorly). It consist of ciliary muscles and ciliary processes. Each ciliary process (fold) is covered by a double-layered secretory epithelium; the outer pigmented and the inner unpigmented (closes to the lens). The epithelial layers of the ciliary body comes from the retina of the optic cup. We see two different ciliary body epithelium: the inner non-pigmented ciliary epithelium which is connected with the neural retina and the outer pigmented ciliary epithelium which is connected with the retinal pigmented epithelium. The epithelium of the iris is the further anterior extension. The epithelial layers are associated with a stroma containing the ciliary muscle. The ciliary muscle is complex, but can be divided into three portions; anterior, posterior and internal <ref><pubmed>12127103</pubmed></ref>.

In the chick eye development, we see the mesenchyme grow together on the margin of the optic cup and will form the stroma of the ciliary body and the iris, which is located more anteriorly. It is unknown how if the lens has a role in inducing the secretory ciliary body epithelium and the muscular iris epithelium <ref><pubmed>17275804</pubmed></ref>.

=== Iris ===

The Iris develops at the end of the third month of development. The iris is a thin layer and derives from the anterior rim of the optic cup. In the anterior of the eye, the optic epithelium is nonneural and matures as ciliary body and iris epithelia.

=== Cornea ===

http://www.sciencedirect.com/science/article/pii/S1877117315000642

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1298807/pdf/taos00013-0203.pdf

=== Aqueous Chambers ===
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=== Choroid and Sclera ===
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<ref><pubmed>23528534</pubmed></ref>

=== Eyelids ===

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=== Lacrimal Glands ===

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=== Extraocular muscles ===
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<pubmed>26410132</pubmed>
<pubmed>23071378</pubmed>

We could talk briefly in this sections about the causes of short/long-sightedness and common causes of blindness at a developmental level - z3416557

== Congenital Anomalies ==
We could talk briefly in this sections about the causes of short/long-sightedness and common causes of blindness at a developmental level - z3416557

Although quite rare, abnormalities can occur during the embryonic development that causes serious effects to the features of the eyes, its function as well as the further normal development after birth. These anomalies can occur unilaterally or bilaterally and it is also common for most reported cases to have more than one type of eye abnormalities at a time. Thus, the estimated prevalence statistics listed in the table can overlap.

{| class="wikitable"
! style="background:#f4a941" | Congenital Anomalies
! style="background:#f4a941" | Description
! style="background:#f4a941" | Epidemiology
|-
| Anopthalmia || The absence of the eyes.
| rowspan="2" | Prevalence: Anophthalmia-Microphthalmia Syndrome was estimated to be 5.3 per 100 000 cases <ref name="Orphanet Report Series - Rare Diseases Collection">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: http://www.orpha.net</ref>
|-
| Microphtalmia || Abnormal reduction in size of the eyeballs.
|-
| Coloboma || A condition where parts of the eye is missing and failed to develop normally.
| Prevalence: Occular coloboma was estimated to be 8.0 per 100 000 cases <ref name="Orphanet Report Series - Rare Diseases Collection">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: http://www.orpha.net</ref>
|-
| Aniridia || Complete or partial absence of the iris.
| Prevalence: Estimated to be 1.5 per 100 000 cases <ref name="Orphanet Report Series - Rare Diseases Collection">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: http://www.orpha.net</ref>
|-
| Optic Nerve Hypoplasia || A condition where the optic nerves are underdeveloped.
| Prevalence: Reported to be the most common abnormality <ref name="The Optic Nerve Hypoplasia">Ryabets-Lienhard, A., Stewart, C., Borchert, M., & Geffner, M. E. (2016). The Optic Nerve Hypoplasia Spectrum - Review of the Literature and Clinical Guidelines. ''Advances in Pediatrics, 63'', 127-146. doi: 10.1016/j.yapd.2016.04.009 </ref>
*10.9 per 100 000 in United Kingdom
*17.3 per 100 000 cases in Sweden.
*6.3% of cases was reported in New Zealand
|-
|}

[[File:Anophthalmia.jpeg|150px|thumb|left|'''Figure 2.''' Anopthalmia birth defect]]
[[File:Microphthalmia-500px.jpg|150px|thumb|centre|'''Figure 3.''' Microphthalmia birth defect]]

==Glossary==

==References==

<references/>

==External links==

z5075309 - <pubmed>26956898</pubmed>

2017 Group Project 4

2017-10-05T03:51:19Z

Z3416557:

{{ANAT2341Project2017header}}

= Eye Development =
[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 16:09, 14 September 2017 (AEST) OK Feedback
* Timelines
* Embryonic contributions from germ layers and neural crest
* Cellular components
* Current research areas
* Get rid of the bold formatting for sub-headings.
* Animal models compared to human development
* Central neural pathway

== Anatomy of the Adult Eye ==

The eye is a complex sensory structure which allows a variety of species to intake and process visual information from the world around us.

To discuss the key anatomical components of the eye, we will break down the eye in parts<ref>aaaa</ref>:

'''Supporting Structures (Orbit, Extraoccular Muscles, Lacrimal Gland, Eyelid)'''
[[File:22292144 10208413540209536 722417340 o.jpg|250px|thumb|right]]
The orbit of the eye consists of a framework of bones and connective tissue which provide structural support and protection to the sensitive human eye. 7 bones contribute to the orbit of the eye: frontal, lacrimal, sphenoid, zygomtatic, ethmoid, maxilary, palatine. Several openings exist in the orbital structure, 2 key fissures are the superior orbital fissure and inferior orbital fissure and the posterior optic canal. These openings allow crainial nerves passageway.

A set of 6 extraoccular muscles allow for a strong voluntary control of the movement of the eye. These muscles include superior recuts, inferior rectus, lateral rectus, medial rectus, inferior oblique, superior oblique muscles. These muscles are some of the smallest in the human body and are designed to produce fast, controlled motion to focus on an object of interest.

The eyelid is the anterior covering of the eye, consisting of a thin fold of skin. It is controlled by the levitator palpabrae superioris muscle. Superio-laterally to the eyelid is the lacrimal gland, which serves to create a film of tear, an important component to keeping the anterior surface of the eye moist. The eyelid assists in this process by opening and closing, or blinking, which spreads the tear film across the surface of the eye. Tear film and debris caught in the tear film are excreted through the lacrimal duct which is located on the infero-medial surface of the eyelid.
[[File:22251179_10208414266827701_870733039_o.jpg|250px|thumb|right]]

'''Layers of the Eyeball (Sclera, Choroid, Retina)'''

The superficial layers of the eyeball is the sclera, a thick fibrous layer which becomes thicker as it extends posteriorly. The sclera is the visible as the white part of our eye. It's function is to provide structural stability to the eye and serves as attachment for some extraoccular insertions. Deep to the sclera is the choroid, a vascular network which provides nourishment to the layers of the eyeball and plays a large role in the growth of the eye. Deep to the choroid is the retina, a network of nerve fibers which transmit visual information. The retina contains 2 types of photoreceptors which convert visible light into nerve impulses. Rods work best in low light environments while cones work best in high light enthronements and detect colour and sharp detail. The retina does not extend to the anterior part of the eyeball, unlike the sclera and choroid layers.

'''Anterior structure (Lens, Cornea, Pupil, Iris, Ciliary Body, Conjunctiva Anterior Chamber)'''

The most anterior component of the eyeball is the cornea, which is a multilayered avascular transparent structure who's major function to the refract light to assist image formation (contributes about 75% of total refraction). Continuous with cornea superiorly and inferiorly is the conjunctiva. Deep to the cornera is the iris, or the coloured ring visible in the eye. The iris consists of 2 muscles which act to enhance and diminish the size of the pupil, a hole in the middle of the iris allowing light to enter the eye. Deep to the pupil and iris is the lens, which is a transparent structure which contributes the other 25% of the eye's refractive power. The lens changes shape through accomodation controlled by the ciliary body muscles. The ciliary body is the anterior extension of the choroid. The function of the lens is to focus images by changing refractive power based on the position and depth of focal objects. In between the anterior surface of the lens and posterior surface of the cornea is the anterior chamber. This chamber is filled with aqueous humor supplied by the ciliary body, who's function is to provide nutrients to ocular structures and maintain intraocular pressure.
[[File:22251314_10208414283908128_862494115_o.jpg|250px|thumb|right]]

'''Posterior structure (Optic Nerve, Optic Disc, Macula, Fovea, Posterior Chamber)'''

In the posterior section of the retina is the macula, a central spot in which a high concentration of cone photoreceptors are found. The direct centre of the macula is called the fovea which contains solely cone photoreceptors. The fovea is only part of the eye which can conduct 'perfect' 20/20 vision. It has a high workload and hence a strong vascular supporting structure. The most posterior part of the eye is the optic nerve (along with the central retinal artery and central retinal vein), which is responsible for transporting nerve impulses to the cerebral cortex for processing. The opening of the optic nerve is called the optic disc, which contains no photoreceptors and is a blind spot of the eye. Between the posterior surface of the lens, the retina and the optic disc is the posterior chamber. The posterior chamber contains a vitreous humour, a jelly like substance with a high viscosity.

==Overview of eye development==

=== Timeline of embryonic development ===

{| class="wikitable"
! style="background:#f4a941" | WEEK
! style="background:#f4a941" | DEVELOPMENT
|-
| 3-4 || Eye fields, Optic vesicles
|-
| 5-6 || Optic Cup, Lens Vesicle, Choroid Fissure, Hyaloid Artery
|-
| 7-8 || Cornea, Anterior Chamber, Pupillary Membrane, Lens, Retina
|-
| 8-10 || Eyelids
|-
| 9-15 || Iris, Ciliary Body
|}

=== Carnegie Stages ===

Carnegie Stages is a system of 23 stages used to describe developmental events of the vertebrate embryo. At stage 10 we see early signs related to eye development <ref><pubmed>7364662</pubmed></ref>.

{| class="wikitable"
! style="background:#f4a941" | STAGE
! style="background:#f4a941" | EVENTS
|-
| Stage 10 (22 days) || The optic primordium has developed. Two small grooves develop on each side of the developing forebrain in the neural folds - this is the optic grooves. The optic placode has begun to develop, which is seen by a small thickening of the surface ectoderm lateral to the hindbrain.
|-
| Stage 11 (24 days) || Optic vesicle begins to form from the optic groove. Otic pit has formed.
|-
| Stage 12 (26 days) || The optic vesicles have extended from the forbrain to the surface ectoderm. The optic vesicle now lies close to the surface ectoderm.
|-
| Stage 13 (28 days) || The optic vesicle interacts with the surface ectoderm and will induce this ectoderm to form the lens placode, which is the precursor of the lens.
|-
| Stage 14 (32 days) || The lens placode is indented by the lens pit and may be cup-shaped.
|-
| Stage 15 (33 days) || The lens pit will close and form a circle that separates from the surface ectoderm and becomes the lens vesicle. The lens vesicle and optic cub lie close to the surface ectoderm, which creates a slight elevation in the region of the eye.
|-
| Stage 16 (37 days ) || First indication of the development of the eyelids.
|-
| Stage 17 (41 days) || Retinal pigment is visible. The eyes are still laterally places, but starts to take a more anterior position. The lower eyelid fold has begun to form.
|-
| Stage 18 (44 days) || Mesenchyme invades the region between the lens epithelium and the surface ectoderm. The eyes has shifted to more anterior position. The groove above and below the eyes are deeper, but have not joined yet. Eyelid folds develop.
|-
| Stage 19 (48 days) || The upper and the lower eyelids now meet at the outer canthus.
|-
| Stage 20 (51 days) || The lens cavity is lost. The upper and lower lids meet laterally and medially. The eyelids now partly cover the eye.
|-
| Stage 21 (52 days) ||
|-
| Stage 22 (54 days) ||
|-
| Stage 23 (57 days) || The face is beginning to look human.
|-
|}

=== Embryonic Contributions ===

The eyes are derived from four sources:

{| class="wikitable"
! style="background:#f4a941" | Embryonic contributions
! style="background:#f4a941" | Eye component
|-
| Neuroectoderm of the forebrain || Retina, Posterior layers of the iris, The optic nerve
|-
| Surface ectoderm of the head || The lens of the eye, The corneal epithelium
|-
| Mesoderm between the neuroectoderm and the surface ectoderm || The fibrous and vascular coats of the eye
|-
| Neural crest cells || Choroid, Sclera, Corneal endothelium
|}

=== Short overview ===

[[File:DevelopmentEye-PMC43029243.jpg|400px|thumb|right|'''Figure 1.''' Stages of lens formation in mouse embryos]]

The eye starts to develop at 22 days. The optic grooves (sulci) appears in the neural folds at the cranial end of the embryo. When the neural fold fuse to form the forebrain, the optic grooves will form optic vesicles. The optic vesicles are continuous cavities from the cavity of the forebrain and project from the wall of the forebrain and into the mesenchyme. The optic vesicle extends from the diencephalon and will come in contact with the surface ectoderm of the head. This induces the formation of a lens placode. The surface ectoderm near the optic vesicles will thicken and form the lens placodes. The lens placodes will sink into the surface ectoderm and form lens pits. The edges of the lens pits will travel towards each other and fuse to form round lens vesicles, which will later lose connection with the surface ectoderm. The optic vesicles do also keep developing - they will form double-walled optic cups which are connected to the brain by the optic stalk. The two layers of the optic cup will differentiate in different directions. The cells of the outer layer will produce melanin pigment and later become the pigmented retina. The cells of the inner layer of the optic cup will proliferate fast and develop glia, ganglion cells, interneurons and light-sensitive photoreceptor neurons. These cells are in the neural retina. The ganglion cells of the retina are neurons that send signal to the brain. The axons of the ganglion cells of the neural retina will grow in the wall of the optic stalk. The cavity in the optic nerve will start disappearing, and instead, the axons of the ganglion cells will form the '''optic nerve'''.
The optic stalk is now the optic nerve <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>

The optic cups will fold inwards around the lens while the lens vesicles have grown inwards so they have fully lost their connection with the surface ectoderm, which locates them in the cavities of the optic cups. The retinal fissures (linear grooves) will develop and cover the ventral surface of the optic cups and down to the optic stalk. The retinal fissures contain vascular mesenchyme and hyaloid blood vessels will develop here. The hyaloid artery supplies the structures in the eye with blood and the hyaloid vein will return the blood from these structures.

'''Formation of the optic vesicle'''

It is a specific area of the neural ectoderm that will become the optic vesicle - this happens because of a group of transcription factors - Six3, Pax6, and Rx1. These transcription factors are expressed in the most anterior tip of the neural plate. This area will split into bilateral regions and form the optic vesicles. The Pax6 protein has shown to be especially important for the development of the lens and retina. This protein is important for photoreceptive cells in all phyla. Pax 6 is also present in the murine forebrain, hindbrain, and nasal placodes, but the eyes are most sensitive its absence <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

The sonic hedgehog gene is important for the separation of the single eye field into two fields. If this gene is inhibited, the eye field will not split which will result in cyclopia, a single eye in the center of the face <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

== Development of the eye components ==

=== Lens ===

Human lens induction occurs at around 28 days and is completed around day 56. The surface ectoderm will thicken near the optic vesicle and create the lens placode and later form the lens vesicle <ref><pubmed>20171212 </pubmed></ref>. Lens cells come from ectoderm and differentiate into either lens fibers or the lens epithelium. The anterior monolayer of epithelial cells of the lens will create the lens epithelium, which makes the sheet of cuboidal epithelium covering the anterior surface of the lens. The posterior lens vesicle cells will produce the linear primary fibre cells aligned parallel to the optic axis. These fibres will create the lens mass and form the embryonic lens nucleus. The lens epithelial cells will keep proliferating and produce new cells which generate a secondary lens fiber cells. This rows of cell will form the outer shells and keep the lens growing throughout life. This makes the eye lens unique - it will have an addition of new cells inside the surrounding capsule all the time <ref><pubmed>25406393</pubmed></ref>.

=== Retina ===
5075778

=== Ciliary Body ===

The ciliary body is a muscular and secretory tissue and is located directly behind the lens. The ciliary body forms part of the anterior segment of the eye and is an important regulator of eye physiology and the vision. The ciliary body produces the aqueous fluid which fills the eyes and nourishes the lens and cornea - this aqueous fluid function to keep the eye in a pressurized and inflated state, which is important the vision.The ciliary body also synthesizes collagenIX and tenasin-C <ref><pubmed>17275804</pubmed></ref>.

The ciliary body extends from the iris root (anteriorly) to the ora serrata (posteriorly). It consist of ciliary muscles and ciliary processes. Each ciliary process (fold) is covered by a double-layered secretory epithelium; the outer pigmented and the inner unpigmented (closes to the lens). The epithelial layers of the ciliary body comes from the retina of the optic cup. We see two different ciliary body epithelium: the inner non-pigmented ciliary epithelium which is connected with the neural retina and the outer pigmented ciliary epithelium which is connected with the retinal pigmented epithelium. The epithelium of the iris is the further anterior extension. The epithelial layers are associated with a stroma containing the ciliary muscle. The ciliary muscle is complex, but can be divided into three portions; anterior, posterior and internal <ref><pubmed>12127103</pubmed></ref>.

In the chick eye development, we see the mesenchyme grow together on the margin of the optic cup and will form the stroma of the ciliary body and the iris, which is located more anteriorly. It is unknown how if the lens has a role in inducing the secretory ciliary body epithelium and the muscular iris epithelium <ref><pubmed>17275804</pubmed></ref>.

=== Iris ===

The Iris develops at the end of the third month of development. The iris is a thin layer and derives from the anterior rim of the optic cup. In the anterior of the eye, the optic epithelium is nonneural and matures as ciliary body and iris epithelia.

=== Cornea ===

http://www.sciencedirect.com/science/article/pii/S1877117315000642

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1298807/pdf/taos00013-0203.pdf

=== Aqueous Chambers ===
5075309

=== Choroid and Sclera ===
5075309

<ref><pubmed>23528534</pubmed></ref>

=== Eyelids ===

5075309

=== Lacrimal Glands ===

5075309

=== Extraocular muscles ===
5075778

<pubmed>26410132</pubmed>
<pubmed>23071378</pubmed>

We could talk briefly in this sections about the causes of short/long-sightedness and common causes of blindness at a developmental level - z3416557

== Congenital Anomalies ==
We could talk briefly in this sections about the causes of short/long-sightedness and common causes of blindness at a developmental level - z3416557

Although quite rare, abnormalities can occur during the embryonic development that causes serious effects to the features of the eyes, its function as well as the further normal development after birth. These anomalies can occur unilaterally or bilaterally and it is also common for most reported cases to have more than one type of eye abnormalities at a time. Thus, the estimated prevalence statistics listed in the table can overlap.

{| class="wikitable"
! style="background:#f4a941" | Congenital Anomalies
! style="background:#f4a941" | Description
! style="background:#f4a941" | Epidemiology
|-
| Anopthalmia || The absence of the eyes.
| rowspan="2" | Prevalence: Anophthalmia-Microphthalmia Syndrome was estimated to be 5.3 per 100 000 cases <ref name="Orphanet Report Series - Rare Diseases Collection">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: http://www.orpha.net</ref>
|-
| Microphtalmia || Abnormal reduction in size of the eyeballs.
|-
| Coloboma || A condition where parts of the eye is missing and failed to develop normally.
| Prevalence: Occular coloboma was estimated to be 8.0 per 100 000 cases <ref name="Orphanet Report Series - Rare Diseases Collection">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: http://www.orpha.net</ref>
|-
| Aniridia || Complete or partial absence of the iris.
| Prevalence: Estimated to be 1.5 per 100 000 cases <ref name="Orphanet Report Series - Rare Diseases Collection">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: http://www.orpha.net</ref>
|-
| Optic Nerve Hypoplasia || A condition where the optic nerves are underdeveloped.
| Prevalence: Reported to be the most common abnormality <ref name="The Optic Nerve Hypoplasia">Ryabets-Lienhard, A., Stewart, C., Borchert, M., & Geffner, M. E. (2016). The Optic Nerve Hypoplasia Spectrum - Review of the Literature and Clinical Guidelines. ''Advances in Pediatrics, 63'', 127-146. doi: 10.1016/j.yapd.2016.04.009 </ref>
*10.9 per 100 000 in United Kingdom
*17.3 per 100 000 cases in Sweden.
*6.3% of cases was reported in New Zealand
|-
|}

[[File:Anophthalmia.jpeg|150px|thumb|left|'''Figure 2.''' Anopthalmia birth defect]]
[[File:Microphthalmia-500px.jpg|150px|thumb|centre|'''Figure 3.''' Microphthalmia birth defect]]

==Glossary==

==References==

<references/>

==External links==

z5075309 - <pubmed>26956898</pubmed>

2017 Group Project 4

2017-10-05T03:49:08Z

Z3416557:

{{ANAT2341Project2017header}}

= Eye Development =
[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 16:09, 14 September 2017 (AEST) OK Feedback
* Timelines
* Embryonic contributions from germ layers and neural crest
* Cellular components
* Current research areas
* Get rid of the bold formatting for sub-headings.
* Animal models compared to human development
* Central neural pathway

== Anatomy of the Adult Eye ==

The eye is a complex sensory structure which allows a variety of species to intake and process visual information from the world around us.

To discuss the key anatomical components of the eye, we will break down the eye in parts:

'''Supporting Structures (Orbit, Extraoccular Muscles, Lacrimal Gland, Eyelid)'''
[[File:22292144 10208413540209536 722417340 o.jpg|250px|thumb|right]]
The orbit of the eye consists of a framework of bones and connective tissue which provide structural support and protection to the sensitive human eye. 7 bones contribute to the orbit of the eye: frontal, lacrimal, sphenoid, zygomtatic, ethmoid, maxilary, palatine. Several openings exist in the orbital structure, 2 key fissures are the superior orbital fissure and inferior orbital fissure and the posterior optic canal. These openings allow crainial nerves passageway.

A set of 6 extraoccular muscles allow for a strong voluntary control of the movement of the eye. These muscles include superior recuts, inferior rectus, lateral rectus, medial rectus, inferior oblique, superior oblique muscles. These muscles are some of the smallest in the human body and are designed to produce fast, controlled motion to focus on an object of interest.

The eyelid is the anterior covering of the eye, consisting of a thin fold of skin. It is controlled by the levitator palpabrae superioris muscle. Superio-laterally to the eyelid is the lacrimal gland, which serves to create a film of tear, an important component to keeping the anterior surface of the eye moist. The eyelid assists in this process by opening and closing, or blinking, which spreads the tear film across the surface of the eye. Tear film and debris caught in the tear film are excreted through the lacrimal duct which is located on the infero-medial surface of the eyelid.
[[File:22251179_10208414266827701_870733039_o.jpg|250px|thumb|right]]

'''Layers of the Eyeball (Sclera, Choroid, Retina)'''

The superficial layers of the eyeball is the sclera, a thick fibrous layer which becomes thicker as it extends posteriorly. The sclera is the visible as the white part of our eye. It's function is to provide structural stability to the eye and serves as attachment for some extraoccular insertions. Deep to the sclera is the choroid, a vascular network which provides nourishment to the layers of the eyeball and plays a large role in the growth of the eye. Deep to the choroid is the retina, a network of nerve fibers which transmit visual information. The retina contains 2 types of photoreceptors which convert visible light into nerve impulses. Rods work best in low light environments while cones work best in high light enthronements and detect colour and sharp detail. The retina does not extend to the anterior part of the eyeball, unlike the sclera and choroid layers.

'''Anterior structure (Lens, Cornea, Pupil, Iris, Ciliary Body, Conjunctiva Anterior Chamber)'''

The most anterior component of the eyeball is the cornea, which is a multilayered avascular transparent structure who's major function to the refract light to assist image formation (contributes about 75% of total refraction). Continuous with cornea superiorly and inferiorly is the conjunctiva. Deep to the cornera is the iris, or the coloured ring visible in the eye. The iris consists of 2 muscles which act to enhance and diminish the size of the pupil, a hole in the middle of the iris allowing light to enter the eye. Deep to the pupil and iris is the lens, which is a transparent structure which contributes the other 25% of the eye's refractive power. The lens changes shape through accomodation controlled by the ciliary body muscles. The ciliary body is the anterior extension of the choroid. The function of the lens is to focus images by changing refractive power based on the position and depth of focal objects. In between the anterior surface of the lens and posterior surface of the cornea is the anterior chamber. This chamber is filled with aqueous humor supplied by the ciliary body, who's function is to provide nutrients to ocular structures and maintain intraocular pressure.
[[File:22251314_10208414283908128_862494115_o.jpg|250px|thumb|right]]

'''Posterior structure (Optic Nerve, Optic Disc, Macula, Fovea, Posterior Chamber)'''

In the posterior section of the retina is the macula, a central spot in which a high concentration of cone photoreceptors are found. The direct centre of the macula is called the fovea which contains solely cone photoreceptors. The fovea is only part of the eye which can conduct 'perfect' 20/20 vision. It has a high workload and hence a strong vascular supporting structure. The most posterior part of the eye is the optic nerve (along with the central retinal artery and central retinal vein), which is responsible for transporting nerve impulses to the cerebral cortex for processing. The opening of the optic nerve is called the optic disc, which contains no photoreceptors and is a blind spot of the eye. Between the posterior surface of the lens, the retina and the optic disc is the posterior chamber. The posterior chamber contains a vitreous humour, a jelly like substance with a high viscosity.

ref: https://ap01-a.alma.exlibrisgroup.com/view/uresolver/61UNSW_INST/openurl?ctx_enc=info:ofi/enc:UTF-8&ctx_id=10_1&ctx_tim=2017-09-07T14%3A11%3A09IST&ctx_ver=Z39.88-2004&url_ctx_fmt=info:ofi/fmt:kev:mtx:ctx&url_ver=Z39.88-2004&rfr_id=info:sid/primo.exlibrisgroup.com-scopus&req_id=&rft_val_fmt=info:ofi/fmt:kev:mtx:book&rft.genre=bookitem&rft.atitle=Anatomy%20of%20the%20eye&rft.jtitle=&rft.btitle=Handbook%20of%20Visual%20Display%20Technology&rft.aulast=Garhart&rft.auinit=C&rft.auinit1=&rft.auinitm=&rft.ausuffix=&rft.au=Garhart,%20C.&rft.aucorp=&rft.date=20120101&rft.volume=1&rft.issue=&rft.part=&rft.quarter=&rft.ssn=&rft.spage=73&rft.epage=82&rft.pages=73-82&rft.artnum=&rft.issn=&rft.eissn=&rft.isbn=9783540795674&rft.sici=&rft.coden=&rft_id=info:doi/10.1007/978-3-540-79567-4_2.1.1&rft.object_id=&rft.eisbn=&rft.edition=&rft.pub=Springer%20Berlin%20Heidelberg&rft.place=&rft.series=&rft.stitle=&rft.bici=&rft_id=info:bibcode/&rft_id=info:hdl/&rft_id=info:lccn/&rft_id=info:oclcnum/&rft_id=info:pmid/&rft_id=info:eric/((addata/eric}}&rft_dat=%3Cscopus%3E2-s2.0-84923867273%3C/scopus%3E,language=eng,view=UNSWS&svc_dat=single_service&env_type=test

==Overview of eye development==

=== Timeline of embryonic development ===

{| class="wikitable"
! style="background:#f4a941" | WEEK
! style="background:#f4a941" | DEVELOPMENT
|-
| 3-4 || Eye fields, Optic vesicles
|-
| 5-6 || Optic Cup, Lens Vesicle, Choroid Fissure, Hyaloid Artery
|-
| 7-8 || Cornea, Anterior Chamber, Pupillary Membrane, Lens, Retina
|-
| 8-10 || Eyelids
|-
| 9-15 || Iris, Ciliary Body
|}

=== Carnegie Stages ===

Carnegie Stages is a system of 23 stages used to describe developmental events of the vertebrate embryo. At stage 10 we see early signs related to eye development <ref><pubmed>7364662</pubmed></ref>.

{| class="wikitable"
! style="background:#f4a941" | STAGE
! style="background:#f4a941" | EVENTS
|-
| Stage 10 (22 days) || The optic primordium has developed. Two small grooves develop on each side of the developing forebrain in the neural folds - this is the optic grooves. The optic placode has begun to develop, which is seen by a small thickening of the surface ectoderm lateral to the hindbrain.
|-
| Stage 11 (24 days) || Optic vesicle begins to form from the optic groove. Otic pit has formed.
|-
| Stage 12 (26 days) || The optic vesicles have extended from the forbrain to the surface ectoderm. The optic vesicle now lies close to the surface ectoderm.
|-
| Stage 13 (28 days) || The optic vesicle interacts with the surface ectoderm and will induce this ectoderm to form the lens placode, which is the precursor of the lens.
|-
| Stage 14 (32 days) || The lens placode is indented by the lens pit and may be cup-shaped.
|-
| Stage 15 (33 days) || The lens pit will close and form a circle that separates from the surface ectoderm and becomes the lens vesicle. The lens vesicle and optic cub lie close to the surface ectoderm, which creates a slight elevation in the region of the eye.
|-
| Stage 16 (37 days ) || First indication of the development of the eyelids.
|-
| Stage 17 (41 days) || Retinal pigment is visible. The eyes are still laterally places, but starts to take a more anterior position. The lower eyelid fold has begun to form.
|-
| Stage 18 (44 days) || Mesenchyme invades the region between the lens epithelium and the surface ectoderm. The eyes has shifted to more anterior position. The groove above and below the eyes are deeper, but have not joined yet. Eyelid folds develop.
|-
| Stage 19 (48 days) || The upper and the lower eyelids now meet at the outer canthus.
|-
| Stage 20 (51 days) || The lens cavity is lost. The upper and lower lids meet laterally and medially. The eyelids now partly cover the eye.
|-
| Stage 21 (52 days) ||
|-
| Stage 22 (54 days) ||
|-
| Stage 23 (57 days) || The face is beginning to look human.
|-
|}

=== Embryonic Contributions ===

The eyes are derived from four sources:

{| class="wikitable"
! style="background:#f4a941" | Embryonic contributions
! style="background:#f4a941" | Eye component
|-
| Neuroectoderm of the forebrain || Retina, Posterior layers of the iris, The optic nerve
|-
| Surface ectoderm of the head || The lens of the eye, The corneal epithelium
|-
| Mesoderm between the neuroectoderm and the surface ectoderm || The fibrous and vascular coats of the eye
|-
| Neural crest cells || Choroid, Sclera, Corneal endothelium
|}

=== Short overview ===

[[File:DevelopmentEye-PMC43029243.jpg|400px|thumb|right|'''Figure 1.''' Stages of lens formation in mouse embryos]]

The eye starts to develop at 22 days. The optic grooves (sulci) appears in the neural folds at the cranial end of the embryo. When the neural fold fuse to form the forebrain, the optic grooves will form optic vesicles. The optic vesicles are continuous cavities from the cavity of the forebrain and project from the wall of the forebrain and into the mesenchyme. The optic vesicle extends from the diencephalon and will come in contact with the surface ectoderm of the head. This induces the formation of a lens placode. The surface ectoderm near the optic vesicles will thicken and form the lens placodes. The lens placodes will sink into the surface ectoderm and form lens pits. The edges of the lens pits will travel towards each other and fuse to form round lens vesicles, which will later lose connection with the surface ectoderm. The optic vesicles do also keep developing - they will form double-walled optic cups which are connected to the brain by the optic stalk. The two layers of the optic cup will differentiate in different directions. The cells of the outer layer will produce melanin pigment and later become the pigmented retina. The cells of the inner layer of the optic cup will proliferate fast and develop glia, ganglion cells, interneurons and light-sensitive photoreceptor neurons. These cells are in the neural retina. The ganglion cells of the retina are neurons that send signal to the brain. The axons of the ganglion cells of the neural retina will grow in the wall of the optic stalk. The cavity in the optic nerve will start disappearing, and instead, the axons of the ganglion cells will form the '''optic nerve'''.
The optic stalk is now the optic nerve <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>

The optic cups will fold inwards around the lens while the lens vesicles have grown inwards so they have fully lost their connection with the surface ectoderm, which locates them in the cavities of the optic cups. The retinal fissures (linear grooves) will develop and cover the ventral surface of the optic cups and down to the optic stalk. The retinal fissures contain vascular mesenchyme and hyaloid blood vessels will develop here. The hyaloid artery supplies the structures in the eye with blood and the hyaloid vein will return the blood from these structures.

'''Formation of the optic vesicle'''

It is a specific area of the neural ectoderm that will become the optic vesicle - this happens because of a group of transcription factors - Six3, Pax6, and Rx1. These transcription factors are expressed in the most anterior tip of the neural plate. This area will split into bilateral regions and form the optic vesicles. The Pax6 protein has shown to be especially important for the development of the lens and retina. This protein is important for photoreceptive cells in all phyla. Pax 6 is also present in the murine forebrain, hindbrain, and nasal placodes, but the eyes are most sensitive its absence <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

The sonic hedgehog gene is important for the separation of the single eye field into two fields. If this gene is inhibited, the eye field will not split which will result in cyclopia, a single eye in the center of the face <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

== Development of the eye components ==

=== Lens ===

Human lens induction occurs at around 28 days and is completed around day 56. The surface ectoderm will thicken near the optic vesicle and create the lens placode and later form the lens vesicle <ref><pubmed>20171212 </pubmed></ref>. Lens cells come from ectoderm and differentiate into either lens fibers or the lens epithelium. The anterior monolayer of epithelial cells of the lens will create the lens epithelium, which makes the sheet of cuboidal epithelium covering the anterior surface of the lens. The posterior lens vesicle cells will produce the linear primary fibre cells aligned parallel to the optic axis. These fibres will create the lens mass and form the embryonic lens nucleus. The lens epithelial cells will keep proliferating and produce new cells which generate a secondary lens fiber cells. This rows of cell will form the outer shells and keep the lens growing throughout life. This makes the eye lens unique - it will have an addition of new cells inside the surrounding capsule all the time <ref><pubmed>25406393</pubmed></ref>.

=== Retina ===
5075778

=== Ciliary Body ===

The ciliary body is a muscular and secretory tissue and is located directly behind the lens. The ciliary body forms part of the anterior segment of the eye and is an important regulator of eye physiology and the vision. The ciliary body produces the aqueous fluid which fills the eyes and nourishes the lens and cornea - this aqueous fluid function to keep the eye in a pressurized and inflated state, which is important the vision.The ciliary body also synthesizes collagenIX and tenasin-C <ref><pubmed>17275804</pubmed></ref>.

The ciliary body extends from the iris root (anteriorly) to the ora serrata (posteriorly). It consist of ciliary muscles and ciliary processes. Each ciliary process (fold) is covered by a double-layered secretory epithelium; the outer pigmented and the inner unpigmented (closes to the lens). The epithelial layers of the ciliary body comes from the retina of the optic cup. We see two different ciliary body epithelium: the inner non-pigmented ciliary epithelium which is connected with the neural retina and the outer pigmented ciliary epithelium which is connected with the retinal pigmented epithelium. The epithelium of the iris is the further anterior extension. The epithelial layers are associated with a stroma containing the ciliary muscle. The ciliary muscle is complex, but can be divided into three portions; anterior, posterior and internal <ref><pubmed>12127103</pubmed></ref>.

In the chick eye development, we see the mesenchyme grow together on the margin of the optic cup and will form the stroma of the ciliary body and the iris, which is located more anteriorly. It is unknown how if the lens has a role in inducing the secretory ciliary body epithelium and the muscular iris epithelium <ref><pubmed>17275804</pubmed></ref>.

=== Iris ===

The Iris develops at the end of the third month of development. The iris is a thin layer and derives from the anterior rim of the optic cup. In the anterior of the eye, the optic epithelium is nonneural and matures as ciliary body and iris epithelia.

=== Cornea ===

http://www.sciencedirect.com/science/article/pii/S1877117315000642

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1298807/pdf/taos00013-0203.pdf

=== Aqueous Chambers ===
5075309

=== Choroid and Sclera ===
5075309

<ref><pubmed>23528534</pubmed></ref>

=== Eyelids ===

5075309

=== Lacrimal Glands ===

5075309

=== Extraocular muscles ===
5075778

<pubmed>26410132</pubmed>
<pubmed>23071378</pubmed>

We could talk briefly in this sections about the causes of short/long-sightedness and common causes of blindness at a developmental level - z3416557

== Congenital Anomalies ==
We could talk briefly in this sections about the causes of short/long-sightedness and common causes of blindness at a developmental level - z3416557

Although quite rare, abnormalities can occur during the embryonic development that causes serious effects to the features of the eyes, its function as well as the further normal development after birth. These anomalies can occur unilaterally or bilaterally and it is also common for most reported cases to have more than one type of eye abnormalities at a time. Thus, the estimated prevalence statistics listed in the table can overlap.

{| class="wikitable"
! style="background:#f4a941" | Congenital Anomalies
! style="background:#f4a941" | Description
! style="background:#f4a941" | Epidemiology
|-
| Anopthalmia || The absence of the eyes.
| rowspan="2" | Prevalence: Anophthalmia-Microphthalmia Syndrome was estimated to be 5.3 per 100 000 cases <ref name="Orphanet Report Series - Rare Diseases Collection">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: http://www.orpha.net</ref>
|-
| Microphtalmia || Abnormal reduction in size of the eyeballs.
|-
| Coloboma || A condition where parts of the eye is missing and failed to develop normally.
| Prevalence: Occular coloboma was estimated to be 8.0 per 100 000 cases <ref name="Orphanet Report Series - Rare Diseases Collection">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: http://www.orpha.net</ref>
|-
| Aniridia || Complete or partial absence of the iris.
| Prevalence: Estimated to be 1.5 per 100 000 cases <ref name="Orphanet Report Series - Rare Diseases Collection">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: http://www.orpha.net</ref>
|-
| Optic Nerve Hypoplasia || A condition where the optic nerves are underdeveloped.
| Prevalence: Reported to be the most common abnormality <ref name="The Optic Nerve Hypoplasia">Ryabets-Lienhard, A., Stewart, C., Borchert, M., & Geffner, M. E. (2016). The Optic Nerve Hypoplasia Spectrum - Review of the Literature and Clinical Guidelines. ''Advances in Pediatrics, 63'', 127-146. doi: 10.1016/j.yapd.2016.04.009 </ref>
*10.9 per 100 000 in United Kingdom
*17.3 per 100 000 cases in Sweden.
*6.3% of cases was reported in New Zealand
|-
|}

[[File:Anophthalmia.jpeg|150px|thumb|left|'''Figure 2.''' Anopthalmia birth defect]]
[[File:Microphthalmia-500px.jpg|150px|thumb|centre|'''Figure 3.''' Microphthalmia birth defect]]

==Glossary==

==References==

<references/>

==External links==

z5075309 - <pubmed>26956898</pubmed>

2017 Group Project 4

2017-10-05T03:47:29Z

Z3416557:

{{ANAT2341Project2017header}}

= Eye Development =
[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 16:09, 14 September 2017 (AEST) OK Feedback
* Timelines
* Embryonic contributions from germ layers and neural crest
* Cellular components
* Current research areas
* Get rid of the bold formatting for sub-headings.
* Animal models compared to human development
* Central neural pathway

== Anatomy of the Adult Eye ==

The eye is a complex sensory structure which allows a variety of species to intake and process visual information from the world around us.

To discuss the key anatomical components of the eye, we will break down the eye in parts:

'''Supporting Structures (Orbit, Extraoccular Muscles, Lacrimal Gland, Eyelid)'''

The orbit of the eye consists of a framework of bones and connective tissue which provide structural support and protection to the sensitive human eye. 7 bones contribute to the orbit of the eye: frontal, lacrimal, sphenoid, zygomtatic, ethmoid, maxilary, palatine. Several openings exist in the orbital structure, 2 key fissures are the superior orbital fissure and inferior orbital fissure and the posterior optic canal. These openings allow crainial nerves passageway.

A set of 6 extraoccular muscles allow for a strong voluntary control of the movement of the eye. These muscles include superior recuts, inferior rectus, lateral rectus, medial rectus, inferior oblique, superior oblique muscles. These muscles are some of the smallest in the human body and are designed to produce fast, controlled motion to focus on an object of interest.

The eyelid is the anterior covering of the eye, consisting of a thin fold of skin. It is controlled by the levitator palpabrae superioris muscle. Superio-laterally to the eyelid is the lacrimal gland, which serves to create a film of tear, an important component to keeping the anterior surface of the eye moist. The eyelid assists in this process by opening and closing, or blinking, which spreads the tear film across the surface of the eye. Tear film and debris caught in the tear film are excreted through the lacrimal duct which is located on the infero-medial surface of the eyelid.

'''Layers of the Eyeball (Sclera, Choroid, Retina)'''
[[File:22292144 10208413540209536 722417340 o.jpg|250px|thumb|right]]
The superficial layers of the eyeball is the sclera, a thick fibrous layer which becomes thicker as it extends posteriorly. The sclera is the visible as the white part of our eye. It's function is to provide structural stability to the eye and serves as attachment for some extraoccular insertions. Deep to the sclera is the choroid, a vascular network which provides nourishment to the layers of the eyeball and plays a large role in the growth of the eye. Deep to the choroid is the retina, a network of nerve fibers which transmit visual information. The retina contains 2 types of photoreceptors which convert visible light into nerve impulses. Rods work best in low light environments while cones work best in high light enthronements and detect colour and sharp detail. The retina does not extend to the anterior part of the eyeball, unlike the sclera and choroid layers.

'''Anterior structure (Lens, Cornea, Pupil, Iris, Ciliary Body, Conjunctiva Anterior Chamber)'''
[[File:22251179_10208414266827701_870733039_o.jpg|250px|thumb|right]]
The most anterior component of the eyeball is the cornea, which is a multilayered avascular transparent structure who's major function to the refract light to assist image formation (contributes about 75% of total refraction). Continuous with cornea superiorly and inferiorly is the conjunctiva. Deep to the cornera is the iris, or the coloured ring visible in the eye. The iris consists of 2 muscles which act to enhance and diminish the size of the pupil, a hole in the middle of the iris allowing light to enter the eye. Deep to the pupil and iris is the lens, which is a transparent structure which contributes the other 25% of the eye's refractive power. The lens changes shape through accomodation controlled by the ciliary body muscles. The ciliary body is the anterior extension of the choroid. The function of the lens is to focus images by changing refractive power based on the position and depth of focal objects. In between the anterior surface of the lens and posterior surface of the cornea is the anterior chamber. This chamber is filled with aqueous humor supplied by the ciliary body, who's function is to provide nutrients to ocular structures and maintain intraocular pressure.

'''Posterior structure (Optic Nerve, Optic Disc, Macula, Fovea, Posterior Chamber)'''
[[File:22251314_10208414283908128_862494115_o|250px|thumb|right]]
In the posterior section of the retina is the macula, a central spot in which a high concentration of cone photoreceptors are found. The direct centre of the macula is called the fovea which contains solely cone photoreceptors. The fovea is only part of the eye which can conduct 'perfect' 20/20 vision. It has a high workload and hence a strong vascular supporting structure. The most posterior part of the eye is the optic nerve (along with the central retinal artery and central retinal vein), which is responsible for transporting nerve impulses to the cerebral cortex for processing. The opening of the optic nerve is called the optic disc, which contains no photoreceptors and is a blind spot of the eye. Between the posterior surface of the lens, the retina and the optic disc is the posterior chamber. The posterior chamber contains a vitreous humour, a jelly like substance with a high viscosity.

ref: https://ap01-a.alma.exlibrisgroup.com/view/uresolver/61UNSW_INST/openurl?ctx_enc=info:ofi/enc:UTF-8&ctx_id=10_1&ctx_tim=2017-09-07T14%3A11%3A09IST&ctx_ver=Z39.88-2004&url_ctx_fmt=info:ofi/fmt:kev:mtx:ctx&url_ver=Z39.88-2004&rfr_id=info:sid/primo.exlibrisgroup.com-scopus&req_id=&rft_val_fmt=info:ofi/fmt:kev:mtx:book&rft.genre=bookitem&rft.atitle=Anatomy%20of%20the%20eye&rft.jtitle=&rft.btitle=Handbook%20of%20Visual%20Display%20Technology&rft.aulast=Garhart&rft.auinit=C&rft.auinit1=&rft.auinitm=&rft.ausuffix=&rft.au=Garhart,%20C.&rft.aucorp=&rft.date=20120101&rft.volume=1&rft.issue=&rft.part=&rft.quarter=&rft.ssn=&rft.spage=73&rft.epage=82&rft.pages=73-82&rft.artnum=&rft.issn=&rft.eissn=&rft.isbn=9783540795674&rft.sici=&rft.coden=&rft_id=info:doi/10.1007/978-3-540-79567-4_2.1.1&rft.object_id=&rft.eisbn=&rft.edition=&rft.pub=Springer%20Berlin%20Heidelberg&rft.place=&rft.series=&rft.stitle=&rft.bici=&rft_id=info:bibcode/&rft_id=info:hdl/&rft_id=info:lccn/&rft_id=info:oclcnum/&rft_id=info:pmid/&rft_id=info:eric/((addata/eric}}&rft_dat=%3Cscopus%3E2-s2.0-84923867273%3C/scopus%3E,language=eng,view=UNSWS&svc_dat=single_service&env_type=test

==Overview of eye development==

=== Timeline of embryonic development ===

{| class="wikitable"
! style="background:#f4a941" | WEEK
! style="background:#f4a941" | DEVELOPMENT
|-
| 3-4 || Eye fields, Optic vesicles
|-
| 5-6 || Optic Cup, Lens Vesicle, Choroid Fissure, Hyaloid Artery
|-
| 7-8 || Cornea, Anterior Chamber, Pupillary Membrane, Lens, Retina
|-
| 8-10 || Eyelids
|-
| 9-15 || Iris, Ciliary Body
|}

=== Carnegie Stages ===

Carnegie Stages is a system of 23 stages used to describe developmental events of the vertebrate embryo. At stage 10 we see early signs related to eye development <ref><pubmed>7364662</pubmed></ref>.

{| class="wikitable"
! style="background:#f4a941" | STAGE
! style="background:#f4a941" | EVENTS
|-
| Stage 10 (22 days) || The optic primordium has developed. Two small grooves develop on each side of the developing forebrain in the neural folds - this is the optic grooves. The optic placode has begun to develop, which is seen by a small thickening of the surface ectoderm lateral to the hindbrain.
|-
| Stage 11 (24 days) || Optic vesicle begins to form from the optic groove. Otic pit has formed.
|-
| Stage 12 (26 days) || The optic vesicles have extended from the forbrain to the surface ectoderm. The optic vesicle now lies close to the surface ectoderm.
|-
| Stage 13 (28 days) || The optic vesicle interacts with the surface ectoderm and will induce this ectoderm to form the lens placode, which is the precursor of the lens.
|-
| Stage 14 (32 days) || The lens placode is indented by the lens pit and may be cup-shaped.
|-
| Stage 15 (33 days) || The lens pit will close and form a circle that separates from the surface ectoderm and becomes the lens vesicle. The lens vesicle and optic cub lie close to the surface ectoderm, which creates a slight elevation in the region of the eye.
|-
| Stage 16 (37 days ) || First indication of the development of the eyelids.
|-
| Stage 17 (41 days) || Retinal pigment is visible. The eyes are still laterally places, but starts to take a more anterior position. The lower eyelid fold has begun to form.
|-
| Stage 18 (44 days) || Mesenchyme invades the region between the lens epithelium and the surface ectoderm. The eyes has shifted to more anterior position. The groove above and below the eyes are deeper, but have not joined yet. Eyelid folds develop.
|-
| Stage 19 (48 days) || The upper and the lower eyelids now meet at the outer canthus.
|-
| Stage 20 (51 days) || The lens cavity is lost. The upper and lower lids meet laterally and medially. The eyelids now partly cover the eye.
|-
| Stage 21 (52 days) ||
|-
| Stage 22 (54 days) ||
|-
| Stage 23 (57 days) || The face is beginning to look human.
|-
|}

=== Embryonic Contributions ===

The eyes are derived from four sources:

{| class="wikitable"
! style="background:#f4a941" | Embryonic contributions
! style="background:#f4a941" | Eye component
|-
| Neuroectoderm of the forebrain || Retina, Posterior layers of the iris, The optic nerve
|-
| Surface ectoderm of the head || The lens of the eye, The corneal epithelium
|-
| Mesoderm between the neuroectoderm and the surface ectoderm || The fibrous and vascular coats of the eye
|-
| Neural crest cells || Choroid, Sclera, Corneal endothelium
|}

=== Short overview ===

[[File:DevelopmentEye-PMC43029243.jpg|400px|thumb|right|'''Figure 1.''' Stages of lens formation in mouse embryos]]

The eye starts to develop at 22 days. The optic grooves (sulci) appears in the neural folds at the cranial end of the embryo. When the neural fold fuse to form the forebrain, the optic grooves will form optic vesicles. The optic vesicles are continuous cavities from the cavity of the forebrain and project from the wall of the forebrain and into the mesenchyme. The optic vesicle extends from the diencephalon and will come in contact with the surface ectoderm of the head. This induces the formation of a lens placode. The surface ectoderm near the optic vesicles will thicken and form the lens placodes. The lens placodes will sink into the surface ectoderm and form lens pits. The edges of the lens pits will travel towards each other and fuse to form round lens vesicles, which will later lose connection with the surface ectoderm. The optic vesicles do also keep developing - they will form double-walled optic cups which are connected to the brain by the optic stalk. The two layers of the optic cup will differentiate in different directions. The cells of the outer layer will produce melanin pigment and later become the pigmented retina. The cells of the inner layer of the optic cup will proliferate fast and develop glia, ganglion cells, interneurons and light-sensitive photoreceptor neurons. These cells are in the neural retina. The ganglion cells of the retina are neurons that send signal to the brain. The axons of the ganglion cells of the neural retina will grow in the wall of the optic stalk. The cavity in the optic nerve will start disappearing, and instead, the axons of the ganglion cells will form the '''optic nerve'''.
The optic stalk is now the optic nerve <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>

The optic cups will fold inwards around the lens while the lens vesicles have grown inwards so they have fully lost their connection with the surface ectoderm, which locates them in the cavities of the optic cups. The retinal fissures (linear grooves) will develop and cover the ventral surface of the optic cups and down to the optic stalk. The retinal fissures contain vascular mesenchyme and hyaloid blood vessels will develop here. The hyaloid artery supplies the structures in the eye with blood and the hyaloid vein will return the blood from these structures.

'''Formation of the optic vesicle'''

It is a specific area of the neural ectoderm that will become the optic vesicle - this happens because of a group of transcription factors - Six3, Pax6, and Rx1. These transcription factors are expressed in the most anterior tip of the neural plate. This area will split into bilateral regions and form the optic vesicles. The Pax6 protein has shown to be especially important for the development of the lens and retina. This protein is important for photoreceptive cells in all phyla. Pax 6 is also present in the murine forebrain, hindbrain, and nasal placodes, but the eyes are most sensitive its absence <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

The sonic hedgehog gene is important for the separation of the single eye field into two fields. If this gene is inhibited, the eye field will not split which will result in cyclopia, a single eye in the center of the face <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

== Development of the eye components ==

=== Lens ===

Human lens induction occurs at around 28 days and is completed around day 56. The surface ectoderm will thicken near the optic vesicle and create the lens placode and later form the lens vesicle <ref><pubmed>20171212 </pubmed></ref>. Lens cells come from ectoderm and differentiate into either lens fibers or the lens epithelium. The anterior monolayer of epithelial cells of the lens will create the lens epithelium, which makes the sheet of cuboidal epithelium covering the anterior surface of the lens. The posterior lens vesicle cells will produce the linear primary fibre cells aligned parallel to the optic axis. These fibres will create the lens mass and form the embryonic lens nucleus. The lens epithelial cells will keep proliferating and produce new cells which generate a secondary lens fiber cells. This rows of cell will form the outer shells and keep the lens growing throughout life. This makes the eye lens unique - it will have an addition of new cells inside the surrounding capsule all the time <ref><pubmed>25406393</pubmed></ref>.

=== Retina ===
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=== Ciliary Body ===

The ciliary body is a muscular and secretory tissue and is located directly behind the lens. The ciliary body forms part of the anterior segment of the eye and is an important regulator of eye physiology and the vision. The ciliary body produces the aqueous fluid which fills the eyes and nourishes the lens and cornea - this aqueous fluid function to keep the eye in a pressurized and inflated state, which is important the vision.The ciliary body also synthesizes collagenIX and tenasin-C <ref><pubmed>17275804</pubmed></ref>.

The ciliary body extends from the iris root (anteriorly) to the ora serrata (posteriorly). It consist of ciliary muscles and ciliary processes. Each ciliary process (fold) is covered by a double-layered secretory epithelium; the outer pigmented and the inner unpigmented (closes to the lens). The epithelial layers of the ciliary body comes from the retina of the optic cup. We see two different ciliary body epithelium: the inner non-pigmented ciliary epithelium which is connected with the neural retina and the outer pigmented ciliary epithelium which is connected with the retinal pigmented epithelium. The epithelium of the iris is the further anterior extension. The epithelial layers are associated with a stroma containing the ciliary muscle. The ciliary muscle is complex, but can be divided into three portions; anterior, posterior and internal <ref><pubmed>12127103</pubmed></ref>.

In the chick eye development, we see the mesenchyme grow together on the margin of the optic cup and will form the stroma of the ciliary body and the iris, which is located more anteriorly. It is unknown how if the lens has a role in inducing the secretory ciliary body epithelium and the muscular iris epithelium <ref><pubmed>17275804</pubmed></ref>.

=== Iris ===

The Iris develops at the end of the third month of development. The iris is a thin layer and derives from the anterior rim of the optic cup. In the anterior of the eye, the optic epithelium is nonneural and matures as ciliary body and iris epithelia.

=== Cornea ===

http://www.sciencedirect.com/science/article/pii/S1877117315000642

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1298807/pdf/taos00013-0203.pdf

=== Aqueous Chambers ===
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=== Choroid and Sclera ===
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<ref><pubmed>23528534</pubmed></ref>

=== Eyelids ===

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=== Lacrimal Glands ===

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=== Extraocular muscles ===
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<pubmed>26410132</pubmed>
<pubmed>23071378</pubmed>

We could talk briefly in this sections about the causes of short/long-sightedness and common causes of blindness at a developmental level - z3416557

== Congenital Anomalies ==
We could talk briefly in this sections about the causes of short/long-sightedness and common causes of blindness at a developmental level - z3416557

Although quite rare, abnormalities can occur during the embryonic development that causes serious effects to the features of the eyes, its function as well as the further normal development after birth. These anomalies can occur unilaterally or bilaterally and it is also common for most reported cases to have more than one type of eye abnormalities at a time. Thus, the estimated prevalence statistics listed in the table can overlap.

{| class="wikitable"
! style="background:#f4a941" | Congenital Anomalies
! style="background:#f4a941" | Description
! style="background:#f4a941" | Epidemiology
|-
| Anopthalmia || The absence of the eyes.
| rowspan="2" | Prevalence: Anophthalmia-Microphthalmia Syndrome was estimated to be 5.3 per 100 000 cases <ref name="Orphanet Report Series - Rare Diseases Collection">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: http://www.orpha.net</ref>
|-
| Microphtalmia || Abnormal reduction in size of the eyeballs.
|-
| Coloboma || A condition where parts of the eye is missing and failed to develop normally.
| Prevalence: Occular coloboma was estimated to be 8.0 per 100 000 cases <ref name="Orphanet Report Series - Rare Diseases Collection">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: http://www.orpha.net</ref>
|-
| Aniridia || Complete or partial absence of the iris.
| Prevalence: Estimated to be 1.5 per 100 000 cases <ref name="Orphanet Report Series - Rare Diseases Collection">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: http://www.orpha.net</ref>
|-
| Optic Nerve Hypoplasia || A condition where the optic nerves are underdeveloped.
| Prevalence: Reported to be the most common abnormality <ref name="The Optic Nerve Hypoplasia">Ryabets-Lienhard, A., Stewart, C., Borchert, M., & Geffner, M. E. (2016). The Optic Nerve Hypoplasia Spectrum - Review of the Literature and Clinical Guidelines. ''Advances in Pediatrics, 63'', 127-146. doi: 10.1016/j.yapd.2016.04.009 </ref>
*10.9 per 100 000 in United Kingdom
*17.3 per 100 000 cases in Sweden.
*6.3% of cases was reported in New Zealand
|-
|}

[[File:Anophthalmia.jpeg|150px|thumb|left|'''Figure 2.''' Anopthalmia birth defect]]
[[File:Microphthalmia-500px.jpg|150px|thumb|centre|'''Figure 3.''' Microphthalmia birth defect]]

==Glossary==

==References==

<references/>

==External links==

z5075309 - <pubmed>26956898</pubmed>

File:22251179 10208414266827701 870733039 o.jpg

2017-10-05T03:47:07Z

Z3416557:

File:22251314 10208414283908128 862494115 o.jpg

2017-10-05T03:46:08Z

Z3416557:

2017 Group Project 4

2017-10-05T03:45:08Z

Z3416557:

{{ANAT2341Project2017header}}

= Eye Development =
[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 16:09, 14 September 2017 (AEST) OK Feedback
* Timelines
* Embryonic contributions from germ layers and neural crest
* Cellular components
* Current research areas
* Get rid of the bold formatting for sub-headings.
* Animal models compared to human development
* Central neural pathway

== Anatomy of the Adult Eye ==

The eye is a complex sensory structure which allows a variety of species to intake and process visual information from the world around us.

To discuss the key anatomical components of the eye, we will break down the eye in parts:

'''Supporting Structures (Orbit, Extraoccular Muscles, Lacrimal Gland, Eyelid)'''

The orbit of the eye consists of a framework of bones and connective tissue which provide structural support and protection to the sensitive human eye. 7 bones contribute to the orbit of the eye: frontal, lacrimal, sphenoid, zygomtatic, ethmoid, maxilary, palatine. Several openings exist in the orbital structure, 2 key fissures are the superior orbital fissure and inferior orbital fissure and the posterior optic canal. These openings allow crainial nerves passageway.

A set of 6 extraoccular muscles allow for a strong voluntary control of the movement of the eye. These muscles include superior recuts, inferior rectus, lateral rectus, medial rectus, inferior oblique, superior oblique muscles. These muscles are some of the smallest in the human body and are designed to produce fast, controlled motion to focus on an object of interest.

The eyelid is the anterior covering of the eye, consisting of a thin fold of skin. It is controlled by the levitator palpabrae superioris muscle. Superio-laterally to the eyelid is the lacrimal gland, which serves to create a film of tear, an important component to keeping the anterior surface of the eye moist. The eyelid assists in this process by opening and closing, or blinking, which spreads the tear film across the surface of the eye. Tear film and debris caught in the tear film are excreted through the lacrimal duct which is located on the infero-medial surface of the eyelid.

'''Layers of the Eyeball (Sclera, Choroid, Retina)'''
[[File:22292144 10208413540209536 722417340 o.jpg|250px|thumb|right]]
The superficial layers of the eyeball is the sclera, a thick fibrous layer which becomes thicker as it extends posteriorly. The sclera is the visible as the white part of our eye. It's function is to provide structural stability to the eye and serves as attachment for some extraoccular insertions. Deep to the sclera is the choroid, a vascular network which provides nourishment to the layers of the eyeball and plays a large role in the growth of the eye. Deep to the choroid is the retina, a network of nerve fibers which transmit visual information. The retina contains 2 types of photoreceptors which convert visible light into nerve impulses. Rods work best in low light environments while cones work best in high light enthronements and detect colour and sharp detail. The retina does not extend to the anterior part of the eyeball, unlike the sclera and choroid layers.

'''Anterior structure (Lens, Cornea, Pupil, Iris, Ciliary Body, Conjunctiva Anterior Chamber)'''
[[File:22292144 10208413540209536 722417340 o.jpg|250px|thumb|right]]]
The most anterior component of the eyeball is the cornea, which is a multilayered avascular transparent structure who's major function to the refract light to assist image formation (contributes about 75% of total refraction). Continuous with cornea superiorly and inferiorly is the conjunctiva. Deep to the cornera is the iris, or the coloured ring visible in the eye. The iris consists of 2 muscles which act to enhance and diminish the size of the pupil, a hole in the middle of the iris allowing light to enter the eye. Deep to the pupil and iris is the lens, which is a transparent structure which contributes the other 25% of the eye's refractive power. The lens changes shape through accomodation controlled by the ciliary body muscles. The ciliary body is the anterior extension of the choroid. The function of the lens is to focus images by changing refractive power based on the position and depth of focal objects. In between the anterior surface of the lens and posterior surface of the cornea is the anterior chamber. This chamber is filled with aqueous humor supplied by the ciliary body, who's function is to provide nutrients to ocular structures and maintain intraocular pressure.

'''Posterior structure (Optic Nerve, Optic Disc, Macula, Fovea, Posterior Chamber)'''
[[File:22292144 10208413540209536 722417340 o.jpg|250px|thumb|right]]]
In the posterior section of the retina is the macula, a central spot in which a high concentration of cone photoreceptors are found. The direct centre of the macula is called the fovea which contains solely cone photoreceptors. The fovea is only part of the eye which can conduct 'perfect' 20/20 vision. It has a high workload and hence a strong vascular supporting structure. The most posterior part of the eye is the optic nerve (along with the central retinal artery and central retinal vein), which is responsible for transporting nerve impulses to the cerebral cortex for processing. The opening of the optic nerve is called the optic disc, which contains no photoreceptors and is a blind spot of the eye. Between the posterior surface of the lens, the retina and the optic disc is the posterior chamber. The posterior chamber contains a vitreous humour, a jelly like substance with a high viscosity.

ref: https://ap01-a.alma.exlibrisgroup.com/view/uresolver/61UNSW_INST/openurl?ctx_enc=info:ofi/enc:UTF-8&ctx_id=10_1&ctx_tim=2017-09-07T14%3A11%3A09IST&ctx_ver=Z39.88-2004&url_ctx_fmt=info:ofi/fmt:kev:mtx:ctx&url_ver=Z39.88-2004&rfr_id=info:sid/primo.exlibrisgroup.com-scopus&req_id=&rft_val_fmt=info:ofi/fmt:kev:mtx:book&rft.genre=bookitem&rft.atitle=Anatomy%20of%20the%20eye&rft.jtitle=&rft.btitle=Handbook%20of%20Visual%20Display%20Technology&rft.aulast=Garhart&rft.auinit=C&rft.auinit1=&rft.auinitm=&rft.ausuffix=&rft.au=Garhart,%20C.&rft.aucorp=&rft.date=20120101&rft.volume=1&rft.issue=&rft.part=&rft.quarter=&rft.ssn=&rft.spage=73&rft.epage=82&rft.pages=73-82&rft.artnum=&rft.issn=&rft.eissn=&rft.isbn=9783540795674&rft.sici=&rft.coden=&rft_id=info:doi/10.1007/978-3-540-79567-4_2.1.1&rft.object_id=&rft.eisbn=&rft.edition=&rft.pub=Springer%20Berlin%20Heidelberg&rft.place=&rft.series=&rft.stitle=&rft.bici=&rft_id=info:bibcode/&rft_id=info:hdl/&rft_id=info:lccn/&rft_id=info:oclcnum/&rft_id=info:pmid/&rft_id=info:eric/((addata/eric}}&rft_dat=%3Cscopus%3E2-s2.0-84923867273%3C/scopus%3E,language=eng,view=UNSWS&svc_dat=single_service&env_type=test

==Overview of eye development==

=== Timeline of embryonic development ===

{| class="wikitable"
! style="background:#f4a941" | WEEK
! style="background:#f4a941" | DEVELOPMENT
|-
| 3-4 || Eye fields, Optic vesicles
|-
| 5-6 || Optic Cup, Lens Vesicle, Choroid Fissure, Hyaloid Artery
|-
| 7-8 || Cornea, Anterior Chamber, Pupillary Membrane, Lens, Retina
|-
| 8-10 || Eyelids
|-
| 9-15 || Iris, Ciliary Body
|}

=== Carnegie Stages ===

Carnegie Stages is a system of 23 stages used to describe developmental events of the vertebrate embryo. At stage 10 we see early signs related to eye development <ref><pubmed>7364662</pubmed></ref>.

{| class="wikitable"
! style="background:#f4a941" | STAGE
! style="background:#f4a941" | EVENTS
|-
| Stage 10 (22 days) || The optic primordium has developed. Two small grooves develop on each side of the developing forebrain in the neural folds - this is the optic grooves. The optic placode has begun to develop, which is seen by a small thickening of the surface ectoderm lateral to the hindbrain.
|-
| Stage 11 (24 days) || Optic vesicle begins to form from the optic groove. Otic pit has formed.
|-
| Stage 12 (26 days) || The optic vesicles have extended from the forbrain to the surface ectoderm. The optic vesicle now lies close to the surface ectoderm.
|-
| Stage 13 (28 days) || The optic vesicle interacts with the surface ectoderm and will induce this ectoderm to form the lens placode, which is the precursor of the lens.
|-
| Stage 14 (32 days) || The lens placode is indented by the lens pit and may be cup-shaped.
|-
| Stage 15 (33 days) || The lens pit will close and form a circle that separates from the surface ectoderm and becomes the lens vesicle. The lens vesicle and optic cub lie close to the surface ectoderm, which creates a slight elevation in the region of the eye.
|-
| Stage 16 (37 days ) || First indication of the development of the eyelids.
|-
| Stage 17 (41 days) || Retinal pigment is visible. The eyes are still laterally places, but starts to take a more anterior position. The lower eyelid fold has begun to form.
|-
| Stage 18 (44 days) || Mesenchyme invades the region between the lens epithelium and the surface ectoderm. The eyes has shifted to more anterior position. The groove above and below the eyes are deeper, but have not joined yet. Eyelid folds develop.
|-
| Stage 19 (48 days) || The upper and the lower eyelids now meet at the outer canthus.
|-
| Stage 20 (51 days) || The lens cavity is lost. The upper and lower lids meet laterally and medially. The eyelids now partly cover the eye.
|-
| Stage 21 (52 days) ||
|-
| Stage 22 (54 days) ||
|-
| Stage 23 (57 days) || The face is beginning to look human.
|-
|}

=== Embryonic Contributions ===

The eyes are derived from four sources:

{| class="wikitable"
! style="background:#f4a941" | Embryonic contributions
! style="background:#f4a941" | Eye component
|-
| Neuroectoderm of the forebrain || Retina, Posterior layers of the iris, The optic nerve
|-
| Surface ectoderm of the head || The lens of the eye, The corneal epithelium
|-
| Mesoderm between the neuroectoderm and the surface ectoderm || The fibrous and vascular coats of the eye
|-
| Neural crest cells || Choroid, Sclera, Corneal endothelium
|}

=== Short overview ===

[[File:DevelopmentEye-PMC43029243.jpg|400px|thumb|right|'''Figure 1.''' Stages of lens formation in mouse embryos]]

The eye starts to develop at 22 days. The optic grooves (sulci) appears in the neural folds at the cranial end of the embryo. When the neural fold fuse to form the forebrain, the optic grooves will form optic vesicles. The optic vesicles are continuous cavities from the cavity of the forebrain and project from the wall of the forebrain and into the mesenchyme. The optic vesicle extends from the diencephalon and will come in contact with the surface ectoderm of the head. This induces the formation of a lens placode. The surface ectoderm near the optic vesicles will thicken and form the lens placodes. The lens placodes will sink into the surface ectoderm and form lens pits. The edges of the lens pits will travel towards each other and fuse to form round lens vesicles, which will later lose connection with the surface ectoderm. The optic vesicles do also keep developing - they will form double-walled optic cups which are connected to the brain by the optic stalk. The two layers of the optic cup will differentiate in different directions. The cells of the outer layer will produce melanin pigment and later become the pigmented retina. The cells of the inner layer of the optic cup will proliferate fast and develop glia, ganglion cells, interneurons and light-sensitive photoreceptor neurons. These cells are in the neural retina. The ganglion cells of the retina are neurons that send signal to the brain. The axons of the ganglion cells of the neural retina will grow in the wall of the optic stalk. The cavity in the optic nerve will start disappearing, and instead, the axons of the ganglion cells will form the '''optic nerve'''.
The optic stalk is now the optic nerve <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>

The optic cups will fold inwards around the lens while the lens vesicles have grown inwards so they have fully lost their connection with the surface ectoderm, which locates them in the cavities of the optic cups. The retinal fissures (linear grooves) will develop and cover the ventral surface of the optic cups and down to the optic stalk. The retinal fissures contain vascular mesenchyme and hyaloid blood vessels will develop here. The hyaloid artery supplies the structures in the eye with blood and the hyaloid vein will return the blood from these structures.

'''Formation of the optic vesicle'''

It is a specific area of the neural ectoderm that will become the optic vesicle - this happens because of a group of transcription factors - Six3, Pax6, and Rx1. These transcription factors are expressed in the most anterior tip of the neural plate. This area will split into bilateral regions and form the optic vesicles. The Pax6 protein has shown to be especially important for the development of the lens and retina. This protein is important for photoreceptive cells in all phyla. Pax 6 is also present in the murine forebrain, hindbrain, and nasal placodes, but the eyes are most sensitive its absence <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

The sonic hedgehog gene is important for the separation of the single eye field into two fields. If this gene is inhibited, the eye field will not split which will result in cyclopia, a single eye in the center of the face <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

== Development of the eye components ==

=== Lens ===

Human lens induction occurs at around 28 days and is completed around day 56. The surface ectoderm will thicken near the optic vesicle and create the lens placode and later form the lens vesicle <ref><pubmed>20171212 </pubmed></ref>. Lens cells come from ectoderm and differentiate into either lens fibers or the lens epithelium. The anterior monolayer of epithelial cells of the lens will create the lens epithelium, which makes the sheet of cuboidal epithelium covering the anterior surface of the lens. The posterior lens vesicle cells will produce the linear primary fibre cells aligned parallel to the optic axis. These fibres will create the lens mass and form the embryonic lens nucleus. The lens epithelial cells will keep proliferating and produce new cells which generate a secondary lens fiber cells. This rows of cell will form the outer shells and keep the lens growing throughout life. This makes the eye lens unique - it will have an addition of new cells inside the surrounding capsule all the time <ref><pubmed>25406393</pubmed></ref>.

=== Retina ===
5075778

=== Ciliary Body ===

The ciliary body is a muscular and secretory tissue and is located directly behind the lens. The ciliary body forms part of the anterior segment of the eye and is an important regulator of eye physiology and the vision. The ciliary body produces the aqueous fluid which fills the eyes and nourishes the lens and cornea - this aqueous fluid function to keep the eye in a pressurized and inflated state, which is important the vision.The ciliary body also synthesizes collagenIX and tenasin-C <ref><pubmed>17275804</pubmed></ref>.

The ciliary body extends from the iris root (anteriorly) to the ora serrata (posteriorly). It consist of ciliary muscles and ciliary processes. Each ciliary process (fold) is covered by a double-layered secretory epithelium; the outer pigmented and the inner unpigmented (closes to the lens). The epithelial layers of the ciliary body comes from the retina of the optic cup. We see two different ciliary body epithelium: the inner non-pigmented ciliary epithelium which is connected with the neural retina and the outer pigmented ciliary epithelium which is connected with the retinal pigmented epithelium. The epithelium of the iris is the further anterior extension. The epithelial layers are associated with a stroma containing the ciliary muscle. The ciliary muscle is complex, but can be divided into three portions; anterior, posterior and internal <ref><pubmed>12127103</pubmed></ref>.

In the chick eye development, we see the mesenchyme grow together on the margin of the optic cup and will form the stroma of the ciliary body and the iris, which is located more anteriorly. It is unknown how if the lens has a role in inducing the secretory ciliary body epithelium and the muscular iris epithelium <ref><pubmed>17275804</pubmed></ref>.

=== Iris ===

The Iris develops at the end of the third month of development. The iris is a thin layer and derives from the anterior rim of the optic cup. In the anterior of the eye, the optic epithelium is nonneural and matures as ciliary body and iris epithelia.

=== Cornea ===

http://www.sciencedirect.com/science/article/pii/S1877117315000642

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1298807/pdf/taos00013-0203.pdf

=== Aqueous Chambers ===
5075309

=== Choroid and Sclera ===
5075309

<ref><pubmed>23528534</pubmed></ref>

=== Eyelids ===

5075309

=== Lacrimal Glands ===

5075309

=== Extraocular muscles ===
5075778

<pubmed>26410132</pubmed>
<pubmed>23071378</pubmed>

We could talk briefly in this sections about the causes of short/long-sightedness and common causes of blindness at a developmental level - z3416557

== Congenital Anomalies ==
We could talk briefly in this sections about the causes of short/long-sightedness and common causes of blindness at a developmental level - z3416557

Although quite rare, abnormalities can occur during the embryonic development that causes serious effects to the features of the eyes, its function as well as the further normal development after birth. These anomalies can occur unilaterally or bilaterally and it is also common for most reported cases to have more than one type of eye abnormalities at a time. Thus, the estimated prevalence statistics listed in the table can overlap.

{| class="wikitable"
! style="background:#f4a941" | Congenital Anomalies
! style="background:#f4a941" | Description
! style="background:#f4a941" | Epidemiology
|-
| Anopthalmia || The absence of the eyes.
| rowspan="2" | Prevalence: Anophthalmia-Microphthalmia Syndrome was estimated to be 5.3 per 100 000 cases <ref name="Orphanet Report Series - Rare Diseases Collection">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: http://www.orpha.net</ref>
|-
| Microphtalmia || Abnormal reduction in size of the eyeballs.
|-
| Coloboma || A condition where parts of the eye is missing and failed to develop normally.
| Prevalence: Occular coloboma was estimated to be 8.0 per 100 000 cases <ref name="Orphanet Report Series - Rare Diseases Collection">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: http://www.orpha.net</ref>
|-
| Aniridia || Complete or partial absence of the iris.
| Prevalence: Estimated to be 1.5 per 100 000 cases <ref name="Orphanet Report Series - Rare Diseases Collection">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: http://www.orpha.net</ref>
|-
| Optic Nerve Hypoplasia || A condition where the optic nerves are underdeveloped.
| Prevalence: Reported to be the most common abnormality <ref name="The Optic Nerve Hypoplasia">Ryabets-Lienhard, A., Stewart, C., Borchert, M., & Geffner, M. E. (2016). The Optic Nerve Hypoplasia Spectrum - Review of the Literature and Clinical Guidelines. ''Advances in Pediatrics, 63'', 127-146. doi: 10.1016/j.yapd.2016.04.009 </ref>
*10.9 per 100 000 in United Kingdom
*17.3 per 100 000 cases in Sweden.
*6.3% of cases was reported in New Zealand
|-
|}

[[File:Anophthalmia.jpeg|150px|thumb|left|'''Figure 2.''' Anopthalmia birth defect]]
[[File:Microphthalmia-500px.jpg|150px|thumb|centre|'''Figure 3.''' Microphthalmia birth defect]]

==Glossary==

==References==

<references/>

==External links==

z5075309 - <pubmed>26956898</pubmed>

2017 Group Project 4

2017-10-05T03:42:47Z

Z3416557:

{{ANAT2341Project2017header}}

= Eye Development =
[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 16:09, 14 September 2017 (AEST) OK Feedback
* Timelines
* Embryonic contributions from germ layers and neural crest
* Cellular components
* Current research areas
* Get rid of the bold formatting for sub-headings.
* Animal models compared to human development
* Central neural pathway

== Anatomy of the Adult Eye ==

The eye is a complex sensory structure which allows a variety of species to intake and process visual information from the world around us.

To discuss the key anatomical components of the eye, we will break down the eye in parts:

'''Supporting Structures (Orbit, Extraoccular Muscles, Lacrimal Gland, Eyelid)'''

The orbit of the eye consists of a framework of bones and connective tissue which provide structural support and protection to the sensitive human eye. 7 bones contribute to the orbit of the eye: frontal, lacrimal, sphenoid, zygomtatic, ethmoid, maxilary, palatine. Several openings exist in the orbital structure, 2 key fissures are the superior orbital fissure and inferior orbital fissure and the posterior optic canal. These openings allow crainial nerves passageway.

A set of 6 extraoccular muscles allow for a strong voluntary control of the movement of the eye. These muscles include superior recuts, inferior rectus, lateral rectus, medial rectus, inferior oblique, superior oblique muscles. These muscles are some of the smallest in the human body and are designed to produce fast, controlled motion to focus on an object of interest.

The eyelid is the anterior covering of the eye, consisting of a thin fold of skin. It is controlled by the levitator palpabrae superioris muscle. Superio-laterally to the eyelid is the lacrimal gland, which serves to create a film of tear, an important component to keeping the anterior surface of the eye moist. The eyelid assists in this process by opening and closing, or blinking, which spreads the tear film across the surface of the eye. Tear film and debris caught in the tear film are excreted through the lacrimal duct which is located on the infero-medial surface of the eyelid.

'''Layers of the Eyeball (Sclera, Choroid, Retina)'''

The superficial layers of the eyeball is the sclera, a thick fibrous layer which becomes thicker as it extends posteriorly. The sclera is the visible as the white part of our eye. It's function is to provide structural stability to the eye and serves as attachment for some extraoccular insertions. Deep to the sclera is the choroid, a vascular network which provides nourishment to the layers of the eyeball and plays a large role in the growth of the eye. Deep to the choroid is the retina, a network of nerve fibers which transmit visual information. The retina contains 2 types of photoreceptors which convert visible light into nerve impulses. Rods work best in low light environments while cones work best in high light enthronements and detect colour and sharp detail. The retina does not extend to the anterior part of the eyeball, unlike the sclera and choroid layers. [[File:22292144 10208413540209536 722417340 o.jpg|200px|thumb|left]]]

'''Anterior structure (Lens, Cornea, Pupil, Iris, Ciliary Body, Conjunctiva Anterior Chamber)'''

The most anterior component of the eyeball is the cornea, which is a multilayered avascular transparent structure who's major function to the refract light to assist image formation (contributes about 75% of total refraction). Continuous with cornea superiorly and inferiorly is the conjunctiva. Deep to the cornera is the iris, or the coloured ring visible in the eye. The iris consists of 2 muscles which act to enhance and diminish the size of the pupil, a hole in the middle of the iris allowing light to enter the eye. Deep to the pupil and iris is the lens, which is a transparent structure which contributes the other 25% of the eye's refractive power. The lens changes shape through accomodation controlled by the ciliary body muscles. The ciliary body is the anterior extension of the choroid. The function of the lens is to focus images by changing refractive power based on the position and depth of focal objects. In between the anterior surface of the lens and posterior surface of the cornea is the anterior chamber. This chamber is filled with aqueous humor supplied by the ciliary body, who's function is to provide nutrients to ocular structures and maintain intraocular pressure.

'''Posterior structure (Optic Nerve, Optic Disc, Macula, Fovea, Posterior Chamber)'''

In the posterior section of the retina is the macula, a central spot in which a high concentration of cone photoreceptors are found. The direct centre of the macula is called the fovea which contains solely cone photoreceptors. The fovea is only part of the eye which can conduct 'perfect' 20/20 vision. It has a high workload and hence a strong vascular supporting structure. The most posterior part of the eye is the optic nerve (along with the central retinal artery and central retinal vein), which is responsible for transporting nerve impulses to the cerebral cortex for processing. The opening of the optic nerve is called the optic disc, which contains no photoreceptors and is a blind spot of the eye. Between the posterior surface of the lens, the retina and the optic disc is the posterior chamber. The posterior chamber contains a vitreous humour, a jelly like substance with a high viscosity.

ref: https://ap01-a.alma.exlibrisgroup.com/view/uresolver/61UNSW_INST/openurl?ctx_enc=info:ofi/enc:UTF-8&ctx_id=10_1&ctx_tim=2017-09-07T14%3A11%3A09IST&ctx_ver=Z39.88-2004&url_ctx_fmt=info:ofi/fmt:kev:mtx:ctx&url_ver=Z39.88-2004&rfr_id=info:sid/primo.exlibrisgroup.com-scopus&req_id=&rft_val_fmt=info:ofi/fmt:kev:mtx:book&rft.genre=bookitem&rft.atitle=Anatomy%20of%20the%20eye&rft.jtitle=&rft.btitle=Handbook%20of%20Visual%20Display%20Technology&rft.aulast=Garhart&rft.auinit=C&rft.auinit1=&rft.auinitm=&rft.ausuffix=&rft.au=Garhart,%20C.&rft.aucorp=&rft.date=20120101&rft.volume=1&rft.issue=&rft.part=&rft.quarter=&rft.ssn=&rft.spage=73&rft.epage=82&rft.pages=73-82&rft.artnum=&rft.issn=&rft.eissn=&rft.isbn=9783540795674&rft.sici=&rft.coden=&rft_id=info:doi/10.1007/978-3-540-79567-4_2.1.1&rft.object_id=&rft.eisbn=&rft.edition=&rft.pub=Springer%20Berlin%20Heidelberg&rft.place=&rft.series=&rft.stitle=&rft.bici=&rft_id=info:bibcode/&rft_id=info:hdl/&rft_id=info:lccn/&rft_id=info:oclcnum/&rft_id=info:pmid/&rft_id=info:eric/((addata/eric}}&rft_dat=%3Cscopus%3E2-s2.0-84923867273%3C/scopus%3E,language=eng,view=UNSWS&svc_dat=single_service&env_type=test

==Overview of eye development==

=== Timeline of embryonic development ===

{| class="wikitable"
! style="background:#f4a941" | WEEK
! style="background:#f4a941" | DEVELOPMENT
|-
| 3-4 || Eye fields, Optic vesicles
|-
| 5-6 || Optic Cup, Lens Vesicle, Choroid Fissure, Hyaloid Artery
|-
| 7-8 || Cornea, Anterior Chamber, Pupillary Membrane, Lens, Retina
|-
| 8-10 || Eyelids
|-
| 9-15 || Iris, Ciliary Body
|}

=== Carnegie Stages ===

Carnegie Stages is a system of 23 stages used to describe developmental events of the vertebrate embryo. At stage 10 we see early signs related to eye development <ref><pubmed>7364662</pubmed></ref>.

{| class="wikitable"
! style="background:#f4a941" | STAGE
! style="background:#f4a941" | EVENTS
|-
| Stage 10 (22 days) || The optic primordium has developed. Two small grooves develop on each side of the developing forebrain in the neural folds - this is the optic grooves. The optic placode has begun to develop, which is seen by a small thickening of the surface ectoderm lateral to the hindbrain.
|-
| Stage 11 (24 days) || Optic vesicle begins to form from the optic groove. Otic pit has formed.
|-
| Stage 12 (26 days) || The optic vesicles have extended from the forbrain to the surface ectoderm. The optic vesicle now lies close to the surface ectoderm.
|-
| Stage 13 (28 days) || The optic vesicle interacts with the surface ectoderm and will induce this ectoderm to form the lens placode, which is the precursor of the lens.
|-
| Stage 14 (32 days) || The lens placode is indented by the lens pit and may be cup-shaped.
|-
| Stage 15 (33 days) || The lens pit will close and form a circle that separates from the surface ectoderm and becomes the lens vesicle. The lens vesicle and optic cub lie close to the surface ectoderm, which creates a slight elevation in the region of the eye.
|-
| Stage 16 (37 days ) || First indication of the development of the eyelids.
|-
| Stage 17 (41 days) || Retinal pigment is visible. The eyes are still laterally places, but starts to take a more anterior position. The lower eyelid fold has begun to form.
|-
| Stage 18 (44 days) || Mesenchyme invades the region between the lens epithelium and the surface ectoderm. The eyes has shifted to more anterior position. The groove above and below the eyes are deeper, but have not joined yet. Eyelid folds develop.
|-
| Stage 19 (48 days) || The upper and the lower eyelids now meet at the outer canthus.
|-
| Stage 20 (51 days) || The lens cavity is lost. The upper and lower lids meet laterally and medially. The eyelids now partly cover the eye.
|-
| Stage 21 (52 days) ||
|-
| Stage 22 (54 days) ||
|-
| Stage 23 (57 days) || The face is beginning to look human.
|-
|}

=== Embryonic Contributions ===

The eyes are derived from four sources:

{| class="wikitable"
! style="background:#f4a941" | Embryonic contributions
! style="background:#f4a941" | Eye component
|-
| Neuroectoderm of the forebrain || Retina, Posterior layers of the iris, The optic nerve
|-
| Surface ectoderm of the head || The lens of the eye, The corneal epithelium
|-
| Mesoderm between the neuroectoderm and the surface ectoderm || The fibrous and vascular coats of the eye
|-
| Neural crest cells || Choroid, Sclera, Corneal endothelium
|}

=== Short overview ===

[[File:DevelopmentEye-PMC43029243.jpg|400px|thumb|right|'''Figure 1.''' Stages of lens formation in mouse embryos]]

The eye starts to develop at 22 days. The optic grooves (sulci) appears in the neural folds at the cranial end of the embryo. When the neural fold fuse to form the forebrain, the optic grooves will form optic vesicles. The optic vesicles are continuous cavities from the cavity of the forebrain and project from the wall of the forebrain and into the mesenchyme. The optic vesicle extends from the diencephalon and will come in contact with the surface ectoderm of the head. This induces the formation of a lens placode. The surface ectoderm near the optic vesicles will thicken and form the lens placodes. The lens placodes will sink into the surface ectoderm and form lens pits. The edges of the lens pits will travel towards each other and fuse to form round lens vesicles, which will later lose connection with the surface ectoderm. The optic vesicles do also keep developing - they will form double-walled optic cups which are connected to the brain by the optic stalk. The two layers of the optic cup will differentiate in different directions. The cells of the outer layer will produce melanin pigment and later become the pigmented retina. The cells of the inner layer of the optic cup will proliferate fast and develop glia, ganglion cells, interneurons and light-sensitive photoreceptor neurons. These cells are in the neural retina. The ganglion cells of the retina are neurons that send signal to the brain. The axons of the ganglion cells of the neural retina will grow in the wall of the optic stalk. The cavity in the optic nerve will start disappearing, and instead, the axons of the ganglion cells will form the '''optic nerve'''.
The optic stalk is now the optic nerve <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>

The optic cups will fold inwards around the lens while the lens vesicles have grown inwards so they have fully lost their connection with the surface ectoderm, which locates them in the cavities of the optic cups. The retinal fissures (linear grooves) will develop and cover the ventral surface of the optic cups and down to the optic stalk. The retinal fissures contain vascular mesenchyme and hyaloid blood vessels will develop here. The hyaloid artery supplies the structures in the eye with blood and the hyaloid vein will return the blood from these structures.

'''Formation of the optic vesicle'''

It is a specific area of the neural ectoderm that will become the optic vesicle - this happens because of a group of transcription factors - Six3, Pax6, and Rx1. These transcription factors are expressed in the most anterior tip of the neural plate. This area will split into bilateral regions and form the optic vesicles. The Pax6 protein has shown to be especially important for the development of the lens and retina. This protein is important for photoreceptive cells in all phyla. Pax 6 is also present in the murine forebrain, hindbrain, and nasal placodes, but the eyes are most sensitive its absence <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

The sonic hedgehog gene is important for the separation of the single eye field into two fields. If this gene is inhibited, the eye field will not split which will result in cyclopia, a single eye in the center of the face <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

== Development of the eye components ==

=== Lens ===

Human lens induction occurs at around 28 days and is completed around day 56. The surface ectoderm will thicken near the optic vesicle and create the lens placode and later form the lens vesicle <ref><pubmed>20171212 </pubmed></ref>. Lens cells come from ectoderm and differentiate into either lens fibers or the lens epithelium. The anterior monolayer of epithelial cells of the lens will create the lens epithelium, which makes the sheet of cuboidal epithelium covering the anterior surface of the lens. The posterior lens vesicle cells will produce the linear primary fibre cells aligned parallel to the optic axis. These fibres will create the lens mass and form the embryonic lens nucleus. The lens epithelial cells will keep proliferating and produce new cells which generate a secondary lens fiber cells. This rows of cell will form the outer shells and keep the lens growing throughout life. This makes the eye lens unique - it will have an addition of new cells inside the surrounding capsule all the time <ref><pubmed>25406393</pubmed></ref>.

=== Retina ===
5075778

=== Ciliary Body ===

The ciliary body is a muscular and secretory tissue and is located directly behind the lens. The ciliary body forms part of the anterior segment of the eye and is an important regulator of eye physiology and the vision. The ciliary body produces the aqueous fluid which fills the eyes and nourishes the lens and cornea - this aqueous fluid function to keep the eye in a pressurized and inflated state, which is important the vision.The ciliary body also synthesizes collagenIX and tenasin-C <ref><pubmed>17275804</pubmed></ref>.

The ciliary body extends from the iris root (anteriorly) to the ora serrata (posteriorly). It consist of ciliary muscles and ciliary processes. Each ciliary process (fold) is covered by a double-layered secretory epithelium; the outer pigmented and the inner unpigmented (closes to the lens). The epithelial layers of the ciliary body comes from the retina of the optic cup. We see two different ciliary body epithelium: the inner non-pigmented ciliary epithelium which is connected with the neural retina and the outer pigmented ciliary epithelium which is connected with the retinal pigmented epithelium. The epithelium of the iris is the further anterior extension. The epithelial layers are associated with a stroma containing the ciliary muscle. The ciliary muscle is complex, but can be divided into three portions; anterior, posterior and internal <ref><pubmed>12127103</pubmed></ref>.

In the chick eye development, we see the mesenchyme grow together on the margin of the optic cup and will form the stroma of the ciliary body and the iris, which is located more anteriorly. It is unknown how if the lens has a role in inducing the secretory ciliary body epithelium and the muscular iris epithelium <ref><pubmed>17275804</pubmed></ref>.

=== Iris ===

The Iris develops at the end of the third month of development. The iris is a thin layer and derives from the anterior rim of the optic cup. In the anterior of the eye, the optic epithelium is nonneural and matures as ciliary body and iris epithelia.

=== Cornea ===

http://www.sciencedirect.com/science/article/pii/S1877117315000642

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1298807/pdf/taos00013-0203.pdf

=== Aqueous Chambers ===
5075309

=== Choroid and Sclera ===
5075309

<ref><pubmed>23528534</pubmed></ref>

=== Eyelids ===

5075309

=== Lacrimal Glands ===

5075309

=== Extraocular muscles ===
5075778

<pubmed>26410132</pubmed>
<pubmed>23071378</pubmed>

We could talk briefly in this sections about the causes of short/long-sightedness and common causes of blindness at a developmental level - z3416557

== Congenital Anomalies ==
We could talk briefly in this sections about the causes of short/long-sightedness and common causes of blindness at a developmental level - z3416557

Although quite rare, abnormalities can occur during the embryonic development that causes serious effects to the features of the eyes, its function as well as the further normal development after birth. These anomalies can occur unilaterally or bilaterally and it is also common for most reported cases to have more than one type of eye abnormalities at a time. Thus, the estimated prevalence statistics listed in the table can overlap.

{| class="wikitable"
! style="background:#f4a941" | Congenital Anomalies
! style="background:#f4a941" | Description
! style="background:#f4a941" | Epidemiology
|-
| Anopthalmia || The absence of the eyes.
| rowspan="2" | Prevalence: Anophthalmia-Microphthalmia Syndrome was estimated to be 5.3 per 100 000 cases <ref name="Orphanet Report Series - Rare Diseases Collection">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: http://www.orpha.net</ref>
|-
| Microphtalmia || Abnormal reduction in size of the eyeballs.
|-
| Coloboma || A condition where parts of the eye is missing and failed to develop normally.
| Prevalence: Occular coloboma was estimated to be 8.0 per 100 000 cases <ref name="Orphanet Report Series - Rare Diseases Collection">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: http://www.orpha.net</ref>
|-
| Aniridia || Complete or partial absence of the iris.
| Prevalence: Estimated to be 1.5 per 100 000 cases <ref name="Orphanet Report Series - Rare Diseases Collection">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: http://www.orpha.net</ref>
|-
| Optic Nerve Hypoplasia || A condition where the optic nerves are underdeveloped.
| Prevalence: Reported to be the most common abnormality <ref name="The Optic Nerve Hypoplasia">Ryabets-Lienhard, A., Stewart, C., Borchert, M., & Geffner, M. E. (2016). The Optic Nerve Hypoplasia Spectrum - Review of the Literature and Clinical Guidelines. ''Advances in Pediatrics, 63'', 127-146. doi: 10.1016/j.yapd.2016.04.009 </ref>
*10.9 per 100 000 in United Kingdom
*17.3 per 100 000 cases in Sweden.
*6.3% of cases was reported in New Zealand
|-
|}

[[File:Anophthalmia.jpeg|150px|thumb|left|'''Figure 2.''' Anopthalmia birth defect]]
[[File:Microphthalmia-500px.jpg|150px|thumb|centre|'''Figure 3.''' Microphthalmia birth defect]]

==Glossary==

==References==

<references/>

==External links==

z5075309 - <pubmed>26956898</pubmed>

2017 Group Project 4

2017-10-05T03:41:14Z

Z3416557:

{{ANAT2341Project2017header}}

= Eye Development =
[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 16:09, 14 September 2017 (AEST) OK Feedback
* Timelines
* Embryonic contributions from germ layers and neural crest
* Cellular components
* Current research areas
* Get rid of the bold formatting for sub-headings.
* Animal models compared to human development
* Central neural pathway

== Anatomy of the Adult Eye ==

The eye is a complex sensory structure which allows a variety of species to intake and process visual information from the world around us.

To discuss the key anatomical components of the eye, we will break down the eye in parts:

'''Supporting Structures (Orbit, Extraoccular Muscles, Lacrimal Gland, Eyelid)'''

The orbit of the eye consists of a framework of bones and connective tissue which provide structural support and protection to the sensitive human eye. 7 bones contribute to the orbit of the eye: frontal, lacrimal, sphenoid, zygomtatic, ethmoid, maxilary, palatine. Several openings exist in the orbital structure, 2 key fissures are the superior orbital fissure and inferior orbital fissure and the posterior optic canal. These openings allow crainial nerves passageway.

A set of 6 extraoccular muscles allow for a strong voluntary control of the movement of the eye. These muscles include superior recuts, inferior rectus, lateral rectus, medial rectus, inferior oblique, superior oblique muscles. These muscles are some of the smallest in the human body and are designed to produce fast, controlled motion to focus on an object of interest.

The eyelid is the anterior covering of the eye, consisting of a thin fold of skin. It is controlled by the levitator palpabrae superioris muscle. Superio-laterally to the eyelid is the lacrimal gland, which serves to create a film of tear, an important component to keeping the anterior surface of the eye moist. The eyelid assists in this process by opening and closing, or blinking, which spreads the tear film across the surface of the eye. Tear film and debris caught in the tear film are excreted through the lacrimal duct which is located on the infero-medial surface of the eyelid.

'''Layers of the Eyeball (Sclera, Choroid, Retina)'''

The superficial layers of the eyeball is the sclera, a thick fibrous layer which becomes thicker as it extends posteriorly. The sclera is the visible as the white part of our eye. It's function is to provide structural stability to the eye and serves as attachment for some extraoccular insertions. Deep to the sclera is the choroid, a vascular network which provides nourishment to the layers of the eyeball and plays a large role in the growth of the eye. Deep to the choroid is the retina, a network of nerve fibers which transmit visual information. The retina contains 2 types of photoreceptors which convert visible light into nerve impulses. Rods work best in low light environments while cones work best in high light enthronements and detect colour and sharp detail. The retina does not extend to the anterior part of the eyeball, unlike the sclera and choroid layers. [[File:22292144 10208413540209536 722417340 o.jpg|upright=0.02]]

'''Anterior structure (Lens, Cornea, Pupil, Iris, Ciliary Body, Conjunctiva Anterior Chamber)'''

The most anterior component of the eyeball is the cornea, which is a multilayered avascular transparent structure who's major function to the refract light to assist image formation (contributes about 75% of total refraction). Continuous with cornea superiorly and inferiorly is the conjunctiva. Deep to the cornera is the iris, or the coloured ring visible in the eye. The iris consists of 2 muscles which act to enhance and diminish the size of the pupil, a hole in the middle of the iris allowing light to enter the eye. Deep to the pupil and iris is the lens, which is a transparent structure which contributes the other 25% of the eye's refractive power. The lens changes shape through accomodation controlled by the ciliary body muscles. The ciliary body is the anterior extension of the choroid. The function of the lens is to focus images by changing refractive power based on the position and depth of focal objects. In between the anterior surface of the lens and posterior surface of the cornea is the anterior chamber. This chamber is filled with aqueous humor supplied by the ciliary body, who's function is to provide nutrients to ocular structures and maintain intraocular pressure.

'''Posterior structure (Optic Nerve, Optic Disc, Macula, Fovea, Posterior Chamber)'''

In the posterior section of the retina is the macula, a central spot in which a high concentration of cone photoreceptors are found. The direct centre of the macula is called the fovea which contains solely cone photoreceptors. The fovea is only part of the eye which can conduct 'perfect' 20/20 vision. It has a high workload and hence a strong vascular supporting structure. The most posterior part of the eye is the optic nerve (along with the central retinal artery and central retinal vein), which is responsible for transporting nerve impulses to the cerebral cortex for processing. The opening of the optic nerve is called the optic disc, which contains no photoreceptors and is a blind spot of the eye. Between the posterior surface of the lens, the retina and the optic disc is the posterior chamber. The posterior chamber contains a vitreous humour, a jelly like substance with a high viscosity.

ref: https://ap01-a.alma.exlibrisgroup.com/view/uresolver/61UNSW_INST/openurl?ctx_enc=info:ofi/enc:UTF-8&ctx_id=10_1&ctx_tim=2017-09-07T14%3A11%3A09IST&ctx_ver=Z39.88-2004&url_ctx_fmt=info:ofi/fmt:kev:mtx:ctx&url_ver=Z39.88-2004&rfr_id=info:sid/primo.exlibrisgroup.com-scopus&req_id=&rft_val_fmt=info:ofi/fmt:kev:mtx:book&rft.genre=bookitem&rft.atitle=Anatomy%20of%20the%20eye&rft.jtitle=&rft.btitle=Handbook%20of%20Visual%20Display%20Technology&rft.aulast=Garhart&rft.auinit=C&rft.auinit1=&rft.auinitm=&rft.ausuffix=&rft.au=Garhart,%20C.&rft.aucorp=&rft.date=20120101&rft.volume=1&rft.issue=&rft.part=&rft.quarter=&rft.ssn=&rft.spage=73&rft.epage=82&rft.pages=73-82&rft.artnum=&rft.issn=&rft.eissn=&rft.isbn=9783540795674&rft.sici=&rft.coden=&rft_id=info:doi/10.1007/978-3-540-79567-4_2.1.1&rft.object_id=&rft.eisbn=&rft.edition=&rft.pub=Springer%20Berlin%20Heidelberg&rft.place=&rft.series=&rft.stitle=&rft.bici=&rft_id=info:bibcode/&rft_id=info:hdl/&rft_id=info:lccn/&rft_id=info:oclcnum/&rft_id=info:pmid/&rft_id=info:eric/((addata/eric}}&rft_dat=%3Cscopus%3E2-s2.0-84923867273%3C/scopus%3E,language=eng,view=UNSWS&svc_dat=single_service&env_type=test

==Overview of eye development==

=== Timeline of embryonic development ===

{| class="wikitable"
! style="background:#f4a941" | WEEK
! style="background:#f4a941" | DEVELOPMENT
|-
| 3-4 || Eye fields, Optic vesicles
|-
| 5-6 || Optic Cup, Lens Vesicle, Choroid Fissure, Hyaloid Artery
|-
| 7-8 || Cornea, Anterior Chamber, Pupillary Membrane, Lens, Retina
|-
| 8-10 || Eyelids
|-
| 9-15 || Iris, Ciliary Body
|}

=== Carnegie Stages ===

Carnegie Stages is a system of 23 stages used to describe developmental events of the vertebrate embryo. At stage 10 we see early signs related to eye development <ref><pubmed>7364662</pubmed></ref>.

{| class="wikitable"
! style="background:#f4a941" | STAGE
! style="background:#f4a941" | EVENTS
|-
| Stage 10 (22 days) || The optic primordium has developed. Two small grooves develop on each side of the developing forebrain in the neural folds - this is the optic grooves. The optic placode has begun to develop, which is seen by a small thickening of the surface ectoderm lateral to the hindbrain.
|-
| Stage 11 (24 days) || Optic vesicle begins to form from the optic groove. Otic pit has formed.
|-
| Stage 12 (26 days) || The optic vesicles have extended from the forbrain to the surface ectoderm. The optic vesicle now lies close to the surface ectoderm.
|-
| Stage 13 (28 days) || The optic vesicle interacts with the surface ectoderm and will induce this ectoderm to form the lens placode, which is the precursor of the lens.
|-
| Stage 14 (32 days) || The lens placode is indented by the lens pit and may be cup-shaped.
|-
| Stage 15 (33 days) || The lens pit will close and form a circle that separates from the surface ectoderm and becomes the lens vesicle. The lens vesicle and optic cub lie close to the surface ectoderm, which creates a slight elevation in the region of the eye.
|-
| Stage 16 (37 days ) || First indication of the development of the eyelids.
|-
| Stage 17 (41 days) || Retinal pigment is visible. The eyes are still laterally places, but starts to take a more anterior position. The lower eyelid fold has begun to form.
|-
| Stage 18 (44 days) || Mesenchyme invades the region between the lens epithelium and the surface ectoderm. The eyes has shifted to more anterior position. The groove above and below the eyes are deeper, but have not joined yet. Eyelid folds develop.
|-
| Stage 19 (48 days) || The upper and the lower eyelids now meet at the outer canthus.
|-
| Stage 20 (51 days) || The lens cavity is lost. The upper and lower lids meet laterally and medially. The eyelids now partly cover the eye.
|-
| Stage 21 (52 days) ||
|-
| Stage 22 (54 days) ||
|-
| Stage 23 (57 days) || The face is beginning to look human.
|-
|}

=== Embryonic Contributions ===

The eyes are derived from four sources:

{| class="wikitable"
! style="background:#f4a941" | Embryonic contributions
! style="background:#f4a941" | Eye component
|-
| Neuroectoderm of the forebrain || Retina, Posterior layers of the iris, The optic nerve
|-
| Surface ectoderm of the head || The lens of the eye, The corneal epithelium
|-
| Mesoderm between the neuroectoderm and the surface ectoderm || The fibrous and vascular coats of the eye
|-
| Neural crest cells || Choroid, Sclera, Corneal endothelium
|}

=== Short overview ===

[[File:DevelopmentEye-PMC43029243.jpg|400px|thumb|right|'''Figure 1.''' Stages of lens formation in mouse embryos]]

The eye starts to develop at 22 days. The optic grooves (sulci) appears in the neural folds at the cranial end of the embryo. When the neural fold fuse to form the forebrain, the optic grooves will form optic vesicles. The optic vesicles are continuous cavities from the cavity of the forebrain and project from the wall of the forebrain and into the mesenchyme. The optic vesicle extends from the diencephalon and will come in contact with the surface ectoderm of the head. This induces the formation of a lens placode. The surface ectoderm near the optic vesicles will thicken and form the lens placodes. The lens placodes will sink into the surface ectoderm and form lens pits. The edges of the lens pits will travel towards each other and fuse to form round lens vesicles, which will later lose connection with the surface ectoderm. The optic vesicles do also keep developing - they will form double-walled optic cups which are connected to the brain by the optic stalk. The two layers of the optic cup will differentiate in different directions. The cells of the outer layer will produce melanin pigment and later become the pigmented retina. The cells of the inner layer of the optic cup will proliferate fast and develop glia, ganglion cells, interneurons and light-sensitive photoreceptor neurons. These cells are in the neural retina. The ganglion cells of the retina are neurons that send signal to the brain. The axons of the ganglion cells of the neural retina will grow in the wall of the optic stalk. The cavity in the optic nerve will start disappearing, and instead, the axons of the ganglion cells will form the '''optic nerve'''.
The optic stalk is now the optic nerve <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>

The optic cups will fold inwards around the lens while the lens vesicles have grown inwards so they have fully lost their connection with the surface ectoderm, which locates them in the cavities of the optic cups. The retinal fissures (linear grooves) will develop and cover the ventral surface of the optic cups and down to the optic stalk. The retinal fissures contain vascular mesenchyme and hyaloid blood vessels will develop here. The hyaloid artery supplies the structures in the eye with blood and the hyaloid vein will return the blood from these structures.

'''Formation of the optic vesicle'''

It is a specific area of the neural ectoderm that will become the optic vesicle - this happens because of a group of transcription factors - Six3, Pax6, and Rx1. These transcription factors are expressed in the most anterior tip of the neural plate. This area will split into bilateral regions and form the optic vesicles. The Pax6 protein has shown to be especially important for the development of the lens and retina. This protein is important for photoreceptive cells in all phyla. Pax 6 is also present in the murine forebrain, hindbrain, and nasal placodes, but the eyes are most sensitive its absence <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

The sonic hedgehog gene is important for the separation of the single eye field into two fields. If this gene is inhibited, the eye field will not split which will result in cyclopia, a single eye in the center of the face <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

== Development of the eye components ==

=== Lens ===

Human lens induction occurs at around 28 days and is completed around day 56. The surface ectoderm will thicken near the optic vesicle and create the lens placode and later form the lens vesicle <ref><pubmed>20171212 </pubmed></ref>. Lens cells come from ectoderm and differentiate into either lens fibers or the lens epithelium. The anterior monolayer of epithelial cells of the lens will create the lens epithelium, which makes the sheet of cuboidal epithelium covering the anterior surface of the lens. The posterior lens vesicle cells will produce the linear primary fibre cells aligned parallel to the optic axis. These fibres will create the lens mass and form the embryonic lens nucleus. The lens epithelial cells will keep proliferating and produce new cells which generate a secondary lens fiber cells. This rows of cell will form the outer shells and keep the lens growing throughout life. This makes the eye lens unique - it will have an addition of new cells inside the surrounding capsule all the time <ref><pubmed>25406393</pubmed></ref>.

=== Retina ===
5075778

=== Ciliary Body ===

The ciliary body is a muscular and secretory tissue and is located directly behind the lens. The ciliary body forms part of the anterior segment of the eye and is an important regulator of eye physiology and the vision. The ciliary body produces the aqueous fluid which fills the eyes and nourishes the lens and cornea - this aqueous fluid function to keep the eye in a pressurized and inflated state, which is important the vision.The ciliary body also synthesizes collagenIX and tenasin-C <ref><pubmed>17275804</pubmed></ref>.

The ciliary body extends from the iris root (anteriorly) to the ora serrata (posteriorly). It consist of ciliary muscles and ciliary processes. Each ciliary process (fold) is covered by a double-layered secretory epithelium; the outer pigmented and the inner unpigmented (closes to the lens). The epithelial layers of the ciliary body comes from the retina of the optic cup. We see two different ciliary body epithelium: the inner non-pigmented ciliary epithelium which is connected with the neural retina and the outer pigmented ciliary epithelium which is connected with the retinal pigmented epithelium. The epithelium of the iris is the further anterior extension. The epithelial layers are associated with a stroma containing the ciliary muscle. The ciliary muscle is complex, but can be divided into three portions; anterior, posterior and internal <ref><pubmed>12127103</pubmed></ref>.

In the chick eye development, we see the mesenchyme grow together on the margin of the optic cup and will form the stroma of the ciliary body and the iris, which is located more anteriorly. It is unknown how if the lens has a role in inducing the secretory ciliary body epithelium and the muscular iris epithelium <ref><pubmed>17275804</pubmed></ref>.

=== Iris ===

The Iris develops at the end of the third month of development. The iris is a thin layer and derives from the anterior rim of the optic cup. In the anterior of the eye, the optic epithelium is nonneural and matures as ciliary body and iris epithelia.

=== Cornea ===

http://www.sciencedirect.com/science/article/pii/S1877117315000642

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1298807/pdf/taos00013-0203.pdf

=== Aqueous Chambers ===
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=== Choroid and Sclera ===
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<ref><pubmed>23528534</pubmed></ref>

=== Eyelids ===

5075309

=== Lacrimal Glands ===

5075309

=== Extraocular muscles ===
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<pubmed>26410132</pubmed>
<pubmed>23071378</pubmed>

We could talk briefly in this sections about the causes of short/long-sightedness and common causes of blindness at a developmental level - z3416557

== Congenital Anomalies ==
We could talk briefly in this sections about the causes of short/long-sightedness and common causes of blindness at a developmental level - z3416557

Although quite rare, abnormalities can occur during the embryonic development that causes serious effects to the features of the eyes, its function as well as the further normal development after birth. These anomalies can occur unilaterally or bilaterally and it is also common for most reported cases to have more than one type of eye abnormalities at a time. Thus, the estimated prevalence statistics listed in the table can overlap.

{| class="wikitable"
! style="background:#f4a941" | Congenital Anomalies
! style="background:#f4a941" | Description
! style="background:#f4a941" | Epidemiology
|-
| Anopthalmia || The absence of the eyes.
| rowspan="2" | Prevalence: Anophthalmia-Microphthalmia Syndrome was estimated to be 5.3 per 100 000 cases <ref name="Orphanet Report Series - Rare Diseases Collection">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: http://www.orpha.net</ref>
|-
| Microphtalmia || Abnormal reduction in size of the eyeballs.
|-
| Coloboma || A condition where parts of the eye is missing and failed to develop normally.
| Prevalence: Occular coloboma was estimated to be 8.0 per 100 000 cases <ref name="Orphanet Report Series - Rare Diseases Collection">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: http://www.orpha.net</ref>
|-
| Aniridia || Complete or partial absence of the iris.
| Prevalence: Estimated to be 1.5 per 100 000 cases <ref name="Orphanet Report Series - Rare Diseases Collection">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: http://www.orpha.net</ref>
|-
| Optic Nerve Hypoplasia || A condition where the optic nerves are underdeveloped.
| Prevalence: Reported to be the most common abnormality <ref name="The Optic Nerve Hypoplasia">Ryabets-Lienhard, A., Stewart, C., Borchert, M., & Geffner, M. E. (2016). The Optic Nerve Hypoplasia Spectrum - Review of the Literature and Clinical Guidelines. ''Advances in Pediatrics, 63'', 127-146. doi: 10.1016/j.yapd.2016.04.009 </ref>
*10.9 per 100 000 in United Kingdom
*17.3 per 100 000 cases in Sweden.
*6.3% of cases was reported in New Zealand
|-
|}

[[File:Anophthalmia.jpeg|150px|thumb|left|'''Figure 2.''' Anopthalmia birth defect]]
[[File:Microphthalmia-500px.jpg|150px|thumb|centre|'''Figure 3.''' Microphthalmia birth defect]]

==Glossary==

==References==

<references/>

==External links==

z5075309 - <pubmed>26956898</pubmed>

File:22292144 10208413540209536 722417340 o.jpg

2017-10-05T03:36:25Z

Z3416557: Layers of the Eyeball

Layers of the Eyeball

2017 Group Project 4

2017-10-05T03:34:52Z

Z3416557: /* Anatomy of the Adult Eye */

{{ANAT2341Project2017header}}

= Eye Development =
[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 16:09, 14 September 2017 (AEST) OK Feedback
* Timelines
* Embryonic contributions from germ layers and neural crest
* Cellular components
* Current research areas
* Get rid of the bold formatting for sub-headings.
* Animal models compared to human development
* Central neural pathway

== Anatomy of the Adult Eye ==

The eye is a complex sensory structure which allows a variety of species to intake and process visual information from the world around us.

To discuss the key anatomical components of the eye, we will break down the eye in parts:

'''Supporting Structures (Orbit, Extraoccular Muscles, Lacrimal Gland, Eyelid)'''

The orbit of the eye consists of a framework of bones and connective tissue which provide structural support and protection to the sensitive human eye. 7 bones contribute to the orbit of the eye: frontal, lacrimal, sphenoid, zygomtatic, ethmoid, maxilary, palatine. Several openings exist in the orbital structure, 2 key fissures are the superior orbital fissure and inferior orbital fissure and the posterior optic canal. These openings allow crainial nerves passageway.

A set of 6 extraoccular muscles allow for a strong voluntary control of the movement of the eye. These muscles include superior recuts, inferior rectus, lateral rectus, medial rectus, inferior oblique, superior oblique muscles. These muscles are some of the smallest in the human body and are designed to produce fast, controlled motion to focus on an object of interest.

The eyelid is the anterior covering of the eye, consisting of a thin fold of skin. It is controlled by the levitator palpabrae superioris muscle. Superio-laterally to the eyelid is the lacrimal gland, which serves to create a film of tear, an important component to keeping the anterior surface of the eye moist. The eyelid assists in this process by opening and closing, or blinking, which spreads the tear film across the surface of the eye. Tear film and debris caught in the tear film are excreted through the lacrimal duct which is located on the infero-medial surface of the eyelid.

'''Layers of the Eyeball (Sclera, Choroid, Retina)'''

The superficial layers of the eyeball is the sclera, a thick fibrous layer which becomes thicker as it extends posteriorly. The sclera is the visible as the white part of our eye. It's function is to provide structural stability to the eye and serves as attachment for some extraoccular insertions. Deep to the sclera is the choroid, a vascular network which provides nourishment to the layers of the eyeball and plays a large role in the growth of the eye. Deep to the choroid is the retina, a network of nerve fibers which transmit visual information. The retina contains 2 types of photoreceptors which convert visible light into nerve impulses. Rods work best in low light environments while cones work best in high light enthronements and detect colour and sharp detail. The retina does not extend to the anterior part of the eyeball, unlike the sclera and choroid layers. [[File:Example.jpg]]

'''Anterior structure (Lens, Cornea, Pupil, Iris, Ciliary Body, Conjunctiva Anterior Chamber)'''

The most anterior component of the eyeball is the cornea, which is a multilayered avascular transparent structure who's major function to the refract light to assist image formation (contributes about 75% of total refraction). Continuous with cornea superiorly and inferiorly is the conjunctiva. Deep to the cornera is the iris, or the coloured ring visible in the eye. The iris consists of 2 muscles which act to enhance and diminish the size of the pupil, a hole in the middle of the iris allowing light to enter the eye. Deep to the pupil and iris is the lens, which is a transparent structure which contributes the other 25% of the eye's refractive power. The lens changes shape through accomodation controlled by the ciliary body muscles. The ciliary body is the anterior extension of the choroid. The function of the lens is to focus images by changing refractive power based on the position and depth of focal objects. In between the anterior surface of the lens and posterior surface of the cornea is the anterior chamber. This chamber is filled with aqueous humor supplied by the ciliary body, who's function is to provide nutrients to ocular structures and maintain intraocular pressure.

'''Posterior structure (Optic Nerve, Optic Disc, Macula, Fovea, Posterior Chamber)'''

In the posterior section of the retina is the macula, a central spot in which a high concentration of cone photoreceptors are found. The direct centre of the macula is called the fovea which contains solely cone photoreceptors. The fovea is only part of the eye which can conduct 'perfect' 20/20 vision. It has a high workload and hence a strong vascular supporting structure. The most posterior part of the eye is the optic nerve (along with the central retinal artery and central retinal vein), which is responsible for transporting nerve impulses to the cerebral cortex for processing. The opening of the optic nerve is called the optic disc, which contains no photoreceptors and is a blind spot of the eye. Between the posterior surface of the lens, the retina and the optic disc is the posterior chamber. The posterior chamber contains a vitreous humour, a jelly like substance with a high viscosity.

ref: https://ap01-a.alma.exlibrisgroup.com/view/uresolver/61UNSW_INST/openurl?ctx_enc=info:ofi/enc:UTF-8&ctx_id=10_1&ctx_tim=2017-09-07T14%3A11%3A09IST&ctx_ver=Z39.88-2004&url_ctx_fmt=info:ofi/fmt:kev:mtx:ctx&url_ver=Z39.88-2004&rfr_id=info:sid/primo.exlibrisgroup.com-scopus&req_id=&rft_val_fmt=info:ofi/fmt:kev:mtx:book&rft.genre=bookitem&rft.atitle=Anatomy%20of%20the%20eye&rft.jtitle=&rft.btitle=Handbook%20of%20Visual%20Display%20Technology&rft.aulast=Garhart&rft.auinit=C&rft.auinit1=&rft.auinitm=&rft.ausuffix=&rft.au=Garhart,%20C.&rft.aucorp=&rft.date=20120101&rft.volume=1&rft.issue=&rft.part=&rft.quarter=&rft.ssn=&rft.spage=73&rft.epage=82&rft.pages=73-82&rft.artnum=&rft.issn=&rft.eissn=&rft.isbn=9783540795674&rft.sici=&rft.coden=&rft_id=info:doi/10.1007/978-3-540-79567-4_2.1.1&rft.object_id=&rft.eisbn=&rft.edition=&rft.pub=Springer%20Berlin%20Heidelberg&rft.place=&rft.series=&rft.stitle=&rft.bici=&rft_id=info:bibcode/&rft_id=info:hdl/&rft_id=info:lccn/&rft_id=info:oclcnum/&rft_id=info:pmid/&rft_id=info:eric/((addata/eric}}&rft_dat=%3Cscopus%3E2-s2.0-84923867273%3C/scopus%3E,language=eng,view=UNSWS&svc_dat=single_service&env_type=test

==Overview of eye development==

=== Timeline of embryonic development ===

{| class="wikitable"
! style="background:#f4a941" | WEEK
! style="background:#f4a941" | DEVELOPMENT
|-
| 3-4 || Eye fields, Optic vesicles
|-
| 5-6 || Optic Cup, Lens Vesicle, Choroid Fissure, Hyaloid Artery
|-
| 7-8 || Cornea, Anterior Chamber, Pupillary Membrane, Lens, Retina
|-
| 8-10 || Eyelids
|-
| 9-15 || Iris, Ciliary Body
|}

=== Carnegie Stages ===

Carnegie Stages is a system of 23 stages used to describe developmental events of the vertebrate embryo. At stage 10 we see early signs related to eye development <ref><pubmed>7364662</pubmed></ref>.

{| class="wikitable"
! style="background:#f4a941" | STAGE
! style="background:#f4a941" | EVENTS
|-
| Stage 10 (22 days) || The optic primordium has developed. Two small grooves develop on each side of the developing forebrain in the neural folds - this is the optic grooves. The optic placode has begun to develop, which is seen by a small thickening of the surface ectoderm lateral to the hindbrain.
|-
| Stage 11 (24 days) || Optic vesicle begins to form from the optic groove. Otic pit has formed.
|-
| Stage 12 (26 days) || The optic vesicles have extended from the forbrain to the surface ectoderm. The optic vesicle now lies close to the surface ectoderm.
|-
| Stage 13 (28 days) || The optic vesicle interacts with the surface ectoderm and will induce this ectoderm to form the lens placode, which is the precursor of the lens.
|-
| Stage 14 (32 days) || The lens placode is indented by the lens pit and may be cup-shaped.
|-
| Stage 15 (33 days) || The lens pit will close and form a circle that separates from the surface ectoderm and becomes the lens vesicle. The lens vesicle and optic cub lie close to the surface ectoderm, which creates a slight elevation in the region of the eye.
|-
| Stage 16 (37 days ) || First indication of the development of the eyelids.
|-
| Stage 17 (41 days) || Retinal pigment is visible. The eyes are still laterally places, but starts to take a more anterior position. The lower eyelid fold has begun to form.
|-
| Stage 18 (44 days) || Mesenchyme invades the region between the lens epithelium and the surface ectoderm. The eyes has shifted to more anterior position. The groove above and below the eyes are deeper, but have not joined yet. Eyelid folds develop.
|-
| Stage 19 (48 days) || The upper and the lower eyelids now meet at the outer canthus.
|-
| Stage 20 (51 days) || The lens cavity is lost. The upper and lower lids meet laterally and medially. The eyelids now partly cover the eye.
|-
| Stage 21 (52 days) ||
|-
| Stage 22 (54 days) ||
|-
| Stage 23 (57 days) || The face is beginning to look human.
|-
|}

=== Embryonic Contributions ===

The eyes are derived from four sources:

{| class="wikitable"
! style="background:#f4a941" | Embryonic contributions
! style="background:#f4a941" | Eye component
|-
| Neuroectoderm of the forebrain || Retina, Posterior layers of the iris, The optic nerve
|-
| Surface ectoderm of the head || The lens of the eye, The corneal epithelium
|-
| Mesoderm between the neuroectoderm and the surface ectoderm || The fibrous and vascular coats of the eye
|-
| Neural crest cells || Choroid, Sclera, Corneal endothelium
|}

=== Short overview ===

[[File:DevelopmentEye-PMC43029243.jpg|400px|thumb|right|'''Figure 1.''' Stages of lens formation in mouse embryos]]

The eye starts to develop at 22 days. The optic grooves (sulci) appears in the neural folds at the cranial end of the embryo. When the neural fold fuse to form the forebrain, the optic grooves will form optic vesicles. The optic vesicles are continuous cavities from the cavity of the forebrain and project from the wall of the forebrain and into the mesenchyme. The optic vesicle extends from the diencephalon and will come in contact with the surface ectoderm of the head. This induces the formation of a lens placode. The surface ectoderm near the optic vesicles will thicken and form the lens placodes. The lens placodes will sink into the surface ectoderm and form lens pits. The edges of the lens pits will travel towards each other and fuse to form round lens vesicles, which will later lose connection with the surface ectoderm. The optic vesicles do also keep developing - they will form double-walled optic cups which are connected to the brain by the optic stalk. The two layers of the optic cup will differentiate in different directions. The cells of the outer layer will produce melanin pigment and later become the pigmented retina. The cells of the inner layer of the optic cup will proliferate fast and develop glia, ganglion cells, interneurons and light-sensitive photoreceptor neurons. These cells are in the neural retina. The ganglion cells of the retina are neurons that send signal to the brain. The axons of the ganglion cells of the neural retina will grow in the wall of the optic stalk. The cavity in the optic nerve will start disappearing, and instead, the axons of the ganglion cells will form the '''optic nerve'''.
The optic stalk is now the optic nerve <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>

The optic cups will fold inwards around the lens while the lens vesicles have grown inwards so they have fully lost their connection with the surface ectoderm, which locates them in the cavities of the optic cups. The retinal fissures (linear grooves) will develop and cover the ventral surface of the optic cups and down to the optic stalk. The retinal fissures contain vascular mesenchyme and hyaloid blood vessels will develop here. The hyaloid artery supplies the structures in the eye with blood and the hyaloid vein will return the blood from these structures.

'''Formation of the optic vesicle'''

It is a specific area of the neural ectoderm that will become the optic vesicle - this happens because of a group of transcription factors - Six3, Pax6, and Rx1. These transcription factors are expressed in the most anterior tip of the neural plate. This area will split into bilateral regions and form the optic vesicles. The Pax6 protein has shown to be especially important for the development of the lens and retina. This protein is important for photoreceptive cells in all phyla. Pax 6 is also present in the murine forebrain, hindbrain, and nasal placodes, but the eyes are most sensitive its absence <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

The sonic hedgehog gene is important for the separation of the single eye field into two fields. If this gene is inhibited, the eye field will not split which will result in cyclopia, a single eye in the center of the face <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

== Development of the eye components ==

=== Lens ===

Human lens induction occurs at around 28 days and is completed around day 56. The surface ectoderm will thicken near the optic vesicle and create the lens placode and later form the lens vesicle <ref><pubmed>20171212 </pubmed></ref>. Lens cells come from ectoderm and differentiate into either lens fibers or the lens epithelium. The anterior monolayer of epithelial cells of the lens will create the lens epithelium, which makes the sheet of cuboidal epithelium covering the anterior surface of the lens. The posterior lens vesicle cells will produce the linear primary fibre cells aligned parallel to the optic axis. These fibres will create the lens mass and form the embryonic lens nucleus. The lens epithelial cells will keep proliferating and produce new cells which generate a secondary lens fiber cells. This rows of cell will form the outer shells and keep the lens growing throughout life. This makes the eye lens unique - it will have an addition of new cells inside the surrounding capsule all the time <ref><pubmed>25406393</pubmed></ref>.

=== Retina ===
5075778

=== Ciliary Body ===

The ciliary body is a muscular and secretory tissue and is located directly behind the lens. The ciliary body forms part of the anterior segment of the eye and is an important regulator of eye physiology and the vision. The ciliary body produces the aqueous fluid which fills the eyes and nourishes the lens and cornea - this aqueous fluid function to keep the eye in a pressurized and inflated state, which is important the vision.The ciliary body also synthesizes collagenIX and tenasin-C <ref><pubmed>17275804</pubmed></ref>.

The ciliary body extends from the iris root (anteriorly) to the ora serrata (posteriorly). It consist of ciliary muscles and ciliary processes. Each ciliary process (fold) is covered by a double-layered secretory epithelium; the outer pigmented and the inner unpigmented (closes to the lens). The epithelial layers of the ciliary body comes from the retina of the optic cup. We see two different ciliary body epithelium: the inner non-pigmented ciliary epithelium which is connected with the neural retina and the outer pigmented ciliary epithelium which is connected with the retinal pigmented epithelium. The epithelium of the iris is the further anterior extension. The epithelial layers are associated with a stroma containing the ciliary muscle. The ciliary muscle is complex, but can be divided into three portions; anterior, posterior and internal <ref><pubmed>12127103</pubmed></ref>.

In the chick eye development, we see the mesenchyme grow together on the margin of the optic cup and will form the stroma of the ciliary body and the iris, which is located more anteriorly. It is unknown how if the lens has a role in inducing the secretory ciliary body epithelium and the muscular iris epithelium <ref><pubmed>17275804</pubmed></ref>.

=== Iris ===

The Iris develops at the end of the third month of development. The iris is a thin layer and derives from the anterior rim of the optic cup. In the anterior of the eye, the optic epithelium is nonneural and matures as ciliary body and iris epithelia.

=== Cornea ===

http://www.sciencedirect.com/science/article/pii/S1877117315000642

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1298807/pdf/taos00013-0203.pdf

=== Aqueous Chambers ===
5075309

=== Choroid and Sclera ===
5075309

<ref><pubmed>23528534</pubmed></ref>

=== Eyelids ===

5075309

=== Lacrimal Glands ===

5075309

=== Extraocular muscles ===
5075778

<pubmed>26410132</pubmed>
<pubmed>23071378</pubmed>

We could talk briefly in this sections about the causes of short/long-sightedness and common causes of blindness at a developmental level - z3416557

== Congenital Anomalies ==
We could talk briefly in this sections about the causes of short/long-sightedness and common causes of blindness at a developmental level - z3416557

Although quite rare, abnormalities can occur during the embryonic development that causes serious effects to the features of the eyes, its function as well as the further normal development after birth. These anomalies can occur unilaterally or bilaterally and it is also common for most reported cases to have more than one type of eye abnormalities at a time. Thus, the estimated prevalence statistics listed in the table can overlap.

{| class="wikitable"
! style="background:#f4a941" | Congenital Anomalies
! style="background:#f4a941" | Description
! style="background:#f4a941" | Epidemiology
|-
| Anopthalmia || The absence of the eyes.
| rowspan="2" | Prevalence: Anophthalmia-Microphthalmia Syndrome was estimated to be 5.3 per 100 000 cases <ref name="Orphanet Report Series - Rare Diseases Collection">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: http://www.orpha.net</ref>
|-
| Microphtalmia || Abnormal reduction in size of the eyeballs.
|-
| Coloboma || A condition where parts of the eye is missing and failed to develop normally.
| Prevalence: Occular coloboma was estimated to be 8.0 per 100 000 cases <ref name="Orphanet Report Series - Rare Diseases Collection">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: http://www.orpha.net</ref>
|-
| Aniridia || Complete or partial absence of the iris.
| Prevalence: Estimated to be 1.5 per 100 000 cases <ref name="Orphanet Report Series - Rare Diseases Collection">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: http://www.orpha.net</ref>
|-
| Optic Nerve Hypoplasia || A condition where the optic nerves are underdeveloped.
| Prevalence: Reported to be the most common abnormality <ref name="The Optic Nerve Hypoplasia">Ryabets-Lienhard, A., Stewart, C., Borchert, M., & Geffner, M. E. (2016). The Optic Nerve Hypoplasia Spectrum - Review of the Literature and Clinical Guidelines. ''Advances in Pediatrics, 63'', 127-146. doi: 10.1016/j.yapd.2016.04.009 </ref>
*10.9 per 100 000 in United Kingdom
*17.3 per 100 000 cases in Sweden.
*6.3% of cases was reported in New Zealand
|-
|}

[[File:Anophthalmia.jpeg|150px|thumb|left|'''Figure 2.''' Anopthalmia birth defect]]
[[File:Microphthalmia-500px.jpg|150px|thumb|centre|'''Figure 3.''' Microphthalmia birth defect]]

==Glossary==

==References==

<references/>

==External links==

z5075309 - <pubmed>26956898</pubmed>

2017 Group Project 4

2017-10-05T03:01:37Z

Z3416557: /* Anatomy of the Adult Eye */

{{ANAT2341Project2017header}}

= Eye Development =
[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 16:09, 14 September 2017 (AEST) OK Feedback
* Timelines
* Embryonic contributions from germ layers and neural crest
* Cellular components
* Current research areas
* Get rid of the bold formatting for sub-headings.
* Animal models compared to human development
* Central neural pathway

== Anatomy of the Adult Eye ==

The eye is a complex sensory structure which allows a variety of species to intake and process visual information from the world around us.

To discuss the key anatomical components of the eye, we will break down the eye in parts:

'''Supporting Structures (Orbit, Extraoccular Muscles, Lacrimal Gland, Eyelid)'''

The orbit of the eye consists of a framework of bones and connective tissue which provide structural support and protection to the sensitive human eye. 7 bones contribute to the orbit of the eye: frontal, lacrimal, sphenoid, zygomtatic, ethmoid, maxilary, palatine. Several openings exist in the orbital structure, 2 key fissures are the superior orbital fissure and inferior orbital fissure and the posterior optic canal. These openings allow crainial nerves passageway.

A set of 6 extraoccular muscles allow for a strong voluntary control of the movement of the eye. These muscles include superior recuts, inferior rectus, lateral rectus, medial rectus, inferior oblique, superior oblique muscles. These muscles are some of the smallest in the human body and are designed to produce fast, controlled motion to focus on an object of interest.

The eyelid is the anterior covering of the eye, consisting of a thin fold of skin. It is controlled by the levitator palpabrae superioris muscle. Superio-laterally to the eyelid is the lacrimal gland, which serves to create a film of tear, an important component to keeping the anterior surface of the eye moist. The eyelid assists in this process by opening and closing, or blinking, which spreads the tear film across the surface of the eye. Tear film and debris caught in the tear film are excreted through the lacrimal duct which is located on the infero-medial surface of the eyelid.

'''Layers of the Eyeball (Sclera, Choroid, Retina)'''

The superficial layers of the eyeball is the sclera, a thick fibrous layer which becomes thicker as it extends posteriorly. The sclera is the visible as the white part of our eye. It's function is to provide structural stability to the eye and serves as attachment for some extraoccular insertions. Deep to the sclera is the choroid, a vascular network which provides nourishment to the layers of the eyeball and plays a large role in the growth of the eye. Deep to the choroid is the retina, a network of nerve fibers which transmit visual information. The retina contains 2 types of photoreceptors which convert visible light into nerve impulses. Rods work best in low light environments while cones work best in high light enthronements and detect colour and sharp detail. The retina does not extend to the anterior part of the eyeball, unlike the sclera and choroid layers.

'''Anterior structure (Lens, Cornea, Pupil, Iris, Ciliary Body, Anterior Chamber)'''

The most anterior component of the eye is the cornea, which is a multilayered avascular transparent structure who's major function to the refract light to assist image formation (contributes about 75% of total refraction). Deep to the cornera is the iris, or the coloured ring visible in the eye. The iris consists of 2 muscles which act to enhance and diminish the size of the pupil, a hole in the middle of the iris allowing light to enter the eye. Deep to the pupil and iris is the lens, which is a transparent structure which contribute the other 25% of the eyes refractive power. The lens changes shape through accomodation controlled by the ciliary body muscles. The ciliary body is the anterior extension of the choroid. The function of the lens to focus images by changing refractive power based on the position of focal objects. In between the anterior surface of the lens and posterior surface of the cornea is the anterior chamber. This chamber is filled with aqueous humor supplied by the ciliary body, who's function is to provide nutrients to ocular strcutures and maintain intraoccular pressure.

'''Posterior structure (Optic Nerve, Optic Disc, Macula Lutea)'''

In the posterior section of the retina is the macula, a central spot in which a high concentration of cone photoreceptors are found. The direct centre of the macula is called the fovea which contains solely cone photoreceptors. The fovea is only part of the eye which can conduct 'perfect' 20/20 vision. It has a high workload and hence a strong vascular supporting structure. The most posterior part of the eye is the optic nerve (along with the central retinal artery and central retinal vein)

ref: https://ap01-a.alma.exlibrisgroup.com/view/uresolver/61UNSW_INST/openurl?ctx_enc=info:ofi/enc:UTF-8&ctx_id=10_1&ctx_tim=2017-09-07T14%3A11%3A09IST&ctx_ver=Z39.88-2004&url_ctx_fmt=info:ofi/fmt:kev:mtx:ctx&url_ver=Z39.88-2004&rfr_id=info:sid/primo.exlibrisgroup.com-scopus&req_id=&rft_val_fmt=info:ofi/fmt:kev:mtx:book&rft.genre=bookitem&rft.atitle=Anatomy%20of%20the%20eye&rft.jtitle=&rft.btitle=Handbook%20of%20Visual%20Display%20Technology&rft.aulast=Garhart&rft.auinit=C&rft.auinit1=&rft.auinitm=&rft.ausuffix=&rft.au=Garhart,%20C.&rft.aucorp=&rft.date=20120101&rft.volume=1&rft.issue=&rft.part=&rft.quarter=&rft.ssn=&rft.spage=73&rft.epage=82&rft.pages=73-82&rft.artnum=&rft.issn=&rft.eissn=&rft.isbn=9783540795674&rft.sici=&rft.coden=&rft_id=info:doi/10.1007/978-3-540-79567-4_2.1.1&rft.object_id=&rft.eisbn=&rft.edition=&rft.pub=Springer%20Berlin%20Heidelberg&rft.place=&rft.series=&rft.stitle=&rft.bici=&rft_id=info:bibcode/&rft_id=info:hdl/&rft_id=info:lccn/&rft_id=info:oclcnum/&rft_id=info:pmid/&rft_id=info:eric/((addata/eric}}&rft_dat=%3Cscopus%3E2-s2.0-84923867273%3C/scopus%3E,language=eng,view=UNSWS&svc_dat=single_service&env_type=test

==Overview of eye development==

=== Timeline of embryonic development ===

{| class="wikitable"
! style="background:#f4a941" | WEEK
! style="background:#f4a941" | DEVELOPMENT
|-
| 3-4 || Eye fields, Optic vesicles
|-
| 5-6 || Optic Cup, Lens Vesicle, Choroid Fissure, Hyaloid Artery
|-
| 7-8 || Cornea, Anterior Chamber, Pupillary Membrane, Lens, Retina
|-
| 8-10 || Eyelids
|-
| 9-15 || Iris, Ciliary Body
|}

=== Carnegie Stages ===

Carnegie Stages is a system of 23 stages used to describe developmental events of the vertebrate embryo. At stage 10 we see early signs related to eye development <ref><pubmed>7364662</pubmed></ref>.

{| class="wikitable"
! style="background:#f4a941" | STAGE
! style="background:#f4a941" | EVENTS
|-
| Stage 10 (22 days) || The optic primordium has developed. Two small grooves develop on each side of the developing forebrain in the neural folds - this is the optic grooves. The optic placode has begun to develop, which is seen by a small thickening of the surface ectoderm lateral to the hindbrain.
|-
| Stage 11 (24 days) || Optic vesicle begins to form from the optic groove. Otic pit has formed.
|-
| Stage 12 (26 days) || The optic vesicles have extended from the forbrain to the surface ectoderm. The optic vesicle now lies close to the surface ectoderm.
|-
| Stage 13 (28 days) || The optic vesicle interacts with the surface ectoderm and will induce this ectoderm to form the lens placode, which is the precursor of the lens.
|-
| Stage 14 (32 days) || The lens placode is indented by the lens pit and may be cup-shaped.
|-
| Stage 15 (33 days) || The lens pit will close and form a circle that separates from the surface ectoderm and becomes the lens vesicle. The lens vesicle and optic cub lie close to the surface ectoderm, which creates a slight elevation in the region of the eye.
|-
| Stage 16 (37 days ) || First indication of the development of the eyelids.
|-
| Stage 17 (41 days) || Retinal pigment is visible. The eyes are still laterally places, but starts to take a more anterior position. The lower eyelid fold has begun to form.
|-
| Stage 18 (44 days) || Mesenchyme invades the region between the lens epithelium and the surface ectoderm. The eyes has shifted to more anterior position. The groove above and below the eyes are deeper, but have not joined yet. Eyelid folds develop.
|-
| Stage 19 (48 days) || The upper and the lower eyelids now meet at the outer canthus.
|-
| Stage 20 (51 days) || The lens cavity is lost. The upper and lower lids meet laterally and medially. The eyelids now partly cover the eye.
|-
| Stage 21 (52 days) ||
|-
| Stage 22 (54 days) ||
|-
| Stage 23 (57 days) || The face is beginning to look human.
|-
|}

=== Embryonic Contributions ===

The eyes are derived from four sources:

{| class="wikitable"
! style="background:#f4a941" | Embryonic contributions
! style="background:#f4a941" | Eye component
|-
| Neuroectoderm of the forebrain || Retina, Posterior layers of the iris, The optic nerve
|-
| Surface ectoderm of the head || The lens of the eye, The corneal epithelium
|-
| Mesoderm between the neuroectoderm and the surface ectoderm || The fibrous and vascular coats of the eye
|-
| Neural crest cells || Choroid, Sclera, Corneal endothelium
|}

=== Short overview ===

[[File:DevelopmentEye-PMC43029243.jpg|400px|thumb|right|'''Figure 1.''' Stages of lens formation in mouse embryos]]

The eye starts to develop at 22 days. The optic grooves (sulci) appears in the neural folds at the cranial end of the embryo. When the neural fold fuse to form the forebrain, the optic grooves will form optic vesicles. The optic vesicles are continuous cavities from the cavity of the forebrain and project from the wall of the forebrain and into the mesenchyme. The optic vesicle extends from the diencephalon and will come in contact with the surface ectoderm of the head. This induces the formation of a lens placode. The surface ectoderm near the optic vesicles will thicken and form the lens placodes. The lens placodes will sink into the surface ectoderm and form lens pits. The edges of the lens pits will travel towards each other and fuse to form round lens vesicles, which will later lose connection with the surface ectoderm. The optic vesicles do also keep developing - they will form double-walled optic cups which are connected to the brain by the optic stalk. The two layers of the optic cup will differentiate in different directions. The cells of the outer layer will produce melanin pigment and later become the pigmented retina. The cells of the inner layer of the optic cup will proliferate fast and develop glia, ganglion cells, interneurons and light-sensitive photoreceptor neurons. These cells are in the neural retina. The ganglion cells of the retina are neurons that send signal to the brain. The axons of the ganglion cells of the neural retina will grow in the wall of the optic stalk. The cavity in the optic nerve will start disappearing, and instead, the axons of the ganglion cells will form the '''optic nerve'''.
The optic stalk is now the optic nerve <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>

The optic cups will fold inwards around the lens while the lens vesicles have grown inwards so they have fully lost their connection with the surface ectoderm, which locates them in the cavities of the optic cups. The retinal fissures (linear grooves) will develop and cover the ventral surface of the optic cups and down to the optic stalk. The retinal fissures contain vascular mesenchyme and hyaloid blood vessels will develop here. The hyaloid artery supplies the structures in the eye with blood and the hyaloid vein will return the blood from these structures.

'''Formation of the optic vesicle'''

It is a specific area of the neural ectoderm that will become the optic vesicle - this happens because of a group of transcription factors - Six3, Pax6, and Rx1. These transcription factors are expressed in the most anterior tip of the neural plate. This area will split into bilateral regions and form the optic vesicles. The Pax6 protein has shown to be especially important for the development of the lens and retina. This protein is important for photoreceptive cells in all phyla. Pax 6 is also present in the murine forebrain, hindbrain, and nasal placodes, but the eyes are most sensitive its absence <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

The sonic hedgehog gene is important for the separation of the single eye field into two fields. If this gene is inhibited, the eye field will not split which will result in cyclopia, a single eye in the center of the face <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

== Development of the eye components ==

=== Lens ===

Human lens induction occurs at around 28 days and is completed around day 56. The surface ectoderm will thicken near the optic vesicle and create the lens placode and later form the lens vesicle <ref><pubmed>20171212 </pubmed></ref>. Lens cells come from ectoderm and differentiate into either lens fibers or the lens epithelium. The anterior monolayer of epithelial cells of the lens will create the lens epithelium, which makes the sheet of cuboidal epithelium covering the anterior surface of the lens. The posterior lens vesicle cells will produce the linear primary fibre cells aligned parallel to the optic axis. These fibres will create the lens mass and form the embryonic lens nucleus. The lens epithelial cells will keep proliferating and produce new cells which generate a secondary lens fiber cells. This rows of cell will form the outer shells and keep the lens growing throughout life. This makes the eye lens unique - it will have an addition of new cells inside the surrounding capsule all the time <ref><pubmed>25406393</pubmed></ref>.

=== Retina ===
5075778

=== Ciliary Body ===

The ciliary body is a muscular and secretory tissue and is located directly behind the lens. The ciliary body forms part of the anterior segment of the eye and is an important regulator of eye physiology and the vision. The ciliary body produces the aqueous fluid which fills the eyes and nourishes the lens and cornea - this aqueous fluid function to keep the eye in a pressurized and inflated state, which is important the vision.The ciliary body also synthesizes collagenIX and tenasin-C <ref><pubmed>17275804</pubmed></ref>.

The ciliary body extends from the iris root (anteriorly) to the ora serrata (posteriorly). It consist of ciliary muscles and ciliary processes. Each ciliary process (fold) is covered by a double-layered secretory epithelium; the outer pigmented and the inner unpigmented (closes to the lens). The epithelial layers of the ciliary body comes from the retina of the optic cup. We see two different ciliary body epithelium: the inner non-pigmented ciliary epithelium which is connected with the neural retina and the outer pigmented ciliary epithelium which is connected with the retinal pigmented epithelium. The epithelium of the iris is the further anterior extension. The epithelial layers are associated with a stroma containing the ciliary muscle. The ciliary muscle is complex, but can be divided into three portions; anterior, posterior and internal <ref><pubmed>12127103</pubmed></ref>.

In the chick eye development, we see the mesenchyme grow together on the margin of the optic cup and will form the stroma of the ciliary body and the iris, which is located more anteriorly. It is unknown how if the lens has a role in inducing the secretory ciliary body epithelium and the muscular iris epithelium <ref><pubmed>17275804</pubmed></ref>.

=== Iris ===

The Iris develops at the end of the third month of development. The iris is a thin layer and derives from the anterior rim of the optic cup. In the anterior of the eye, the optic epithelium is nonneural and matures as ciliary body and iris epithelia.

=== Cornea ===

http://www.sciencedirect.com/science/article/pii/S1877117315000642

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1298807/pdf/taos00013-0203.pdf

=== Aqueous Chambers ===
5075309

=== Choroid and Sclera ===
5075309

<ref><pubmed>23528534</pubmed></ref>

=== Eyelids ===

5075309

=== Lacrimal Glands ===

5075309

=== Extraocular muscles ===
5075778

<pubmed>26410132</pubmed>
<pubmed>23071378</pubmed>

We could talk briefly in this sections about the causes of short/long-sightedness and common causes of blindness at a developmental level - z3416557

== Congenital Anomalies ==
We could talk briefly in this sections about the causes of short/long-sightedness and common causes of blindness at a developmental level - z3416557

Although quite rare, abnormalities can occur during the embryonic development that causes serious effects to the features of the eyes, its function as well as the further normal development after birth. These anomalies can occur unilaterally or bilaterally and it is also common for most reported cases to have more than one type of eye abnormalities at a time. Thus, the estimated prevalence statistics listed in the table can overlap.

{| class="wikitable"
! style="background:#f4a941" | Congenital Anomalies
! style="background:#f4a941" | Description
! style="background:#f4a941" | Epidemiology
|-
| Anopthalmia || The absence of the eyes.
| rowspan="2" | Prevalence: Anophthalmia-Microphthalmia Syndrome was estimated to be 5.3 per 100 000 cases <ref name="Orphanet Report Series - Rare Diseases Collection">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: http://www.orpha.net</ref>
|-
| Microphtalmia || Abnormal reduction in size of the eyeballs.
|-
| Coloboma || A condition where parts of the eye is missing and failed to develop normally.
| Prevalence: Occular coloboma was estimated to be 8.0 per 100 000 cases <ref name="Orphanet Report Series - Rare Diseases Collection">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: http://www.orpha.net</ref>
|-
| Aniridia || Complete or partial absence of the iris.
| Prevalence: Estimated to be 1.5 per 100 000 cases <ref name="Orphanet Report Series - Rare Diseases Collection">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: http://www.orpha.net</ref>
|-
| Optic Nerve Hypoplasia || A condition where the optic nerves are underdeveloped.
| Prevalence: Reported to be the most common abnormality <ref name="The Optic Nerve Hypoplasia">Ryabets-Lienhard, A., Stewart, C., Borchert, M., & Geffner, M. E. (2016). The Optic Nerve Hypoplasia Spectrum - Review of the Literature and Clinical Guidelines. ''Advances in Pediatrics, 63'', 127-146. doi: 10.1016/j.yapd.2016.04.009 </ref>
*10.9 per 100 000 in United Kingdom
*17.3 per 100 000 cases in Sweden.
*6.3% of cases was reported in New Zealand
|-
|}

[[File:Anophthalmia.jpeg|150px|thumb|left|'''Figure 2.''' Anopthalmia birth defect]]
[[File:Microphthalmia-500px.jpg|150px|thumb|centre|'''Figure 3.''' Microphthalmia birth defect]]

==Glossary==

==References==

<references/>

==External links==

z5075309 - <pubmed>26956898</pubmed>

2017 Group Project 4

2017-10-05T02:02:03Z

Z3416557: /* Anatomy of the Adult Eye */

{{ANAT2341Project2017header}}

= Eye Development =
[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 16:09, 14 September 2017 (AEST) OK Feedback
* Timelines
* Embryonic contributions from germ layers and neural crest
* Cellular components
* Current research areas
* Get rid of the bold formatting for sub-headings.
* Animal models compared to human development
* Central neural pathway

== Anatomy of the Adult Eye ==

The eye is a complex sensory structure which allows a variety of species to intake and process visual information from the world around us.

To discuss the key anatomical components of the eye, we will break down the eye in parts:

Supporting Structures (Orbit, Extraoccular Muscles, Lacrimal Gland, Eyelid)

The orbit of the eye consists of a framework of bones and connective tissue which provide structural support and protection to the sensitive human eye. 7 bones contribute to the orbit of the eye: frontal, lacrimal, sphenoid, zygomtatic, ethmoid, maxilary, palatine. Several openings exist in the orbital structure, 2 key fissures are the superior orbital fissure and inferior orbital fissure and the posterior optic canal. These openings allow crainial nerves passageway.

A set of 6 extraoccular muscles allow for a strong voluntary control of the movement of the eye. These muscles include superior recuts, inferior rectus, lateral rectus, medial rectus, inferior oblique, superior oblique muscles. These muscles are some of the smallest in the human body and are designed to produce fast, controlled motion to focus on an object of interest.

The eyelid is the anterior covering of the eye, consisting of a thin fold of skin. It is controlled by the levitator palpabrae superioris muscle. Superio-laterally to the eyelid is the lacrimal gland, which serves to create a film of tear, an important component to keeping the anterior surface of the eye moist. The eyelid assists in this process by opening and closing, or blinking, which spreads the tear film across the surface of the eye. Tear film and debris caught in the tear film are excreted through the lacrimal duct which is located on the infero-medial surface of the eyelid.

Layers of the Eyeball (Sclera, Choroid, Retina)

The superficial layers of the eyeball is the sclera, a thick fibrous layer which becomes thicker as it extends posteriorly. The sclera is the visible as the white part of our eye. It's function is to provide structural stability to the eye and serves as attachment for some extraoccular insertions. Deep to the sclera is the choroid, a vascular network which provides nourishment to the layers of the eyeball and plays a large role in the growth of the eye. Deep to the choroid is the retina, a network of nerve fibers which transmit visual information. The retina contains 2 types of photoreceptors which convert visible light into nerve impulses. Rods work best in low light environments while cones work best in high light enthronements and detect colour and sharp detail. The retina does not extend to the anterior part of the eyeball, unlike the sclera and choroid layers.

Anterior structure (Lens, Cornea, Pupil, Iris, Ciliary Body, Anterior Chamber)

The most anterior component of the eye is the cornea, which is a multilayered avascular transparent structure who's major function to the refract light to assist image formation (contributes about 75% of total refraction). Deep to the cornera is the iris, or the coloured ring visible in the eye. The iris consists of 2 muscles which act to enhance and diminish the size of the pupil, a hole in the middle of the iris allowing light to enter the eye. Deep to the pupil and iris is the lens, which is a transparent structure which contribute the other 25% of the eyes refractive power. The lens changes shape through accomodation controlled by the ciliary body muscles. The ciliary body is the anterior extension of the choroid. The function of the lens to focus images by changing refractive power based on the position of focal objects. In between the anterior surface of the lens and posterior surface of the cornea is the anterior chamber. This chamber is filled with aqueous humor supplied by the ciliary body, who's function is to provide nutrients to ocular strcutures and maintain intraoccular pressure.

Posterior structure (Optic Nerve, Optic Disc, Macula Lutea)

ref: https://ap01-a.alma.exlibrisgroup.com/view/uresolver/61UNSW_INST/openurl?ctx_enc=info:ofi/enc:UTF-8&ctx_id=10_1&ctx_tim=2017-09-07T14%3A11%3A09IST&ctx_ver=Z39.88-2004&url_ctx_fmt=info:ofi/fmt:kev:mtx:ctx&url_ver=Z39.88-2004&rfr_id=info:sid/primo.exlibrisgroup.com-scopus&req_id=&rft_val_fmt=info:ofi/fmt:kev:mtx:book&rft.genre=bookitem&rft.atitle=Anatomy%20of%20the%20eye&rft.jtitle=&rft.btitle=Handbook%20of%20Visual%20Display%20Technology&rft.aulast=Garhart&rft.auinit=C&rft.auinit1=&rft.auinitm=&rft.ausuffix=&rft.au=Garhart,%20C.&rft.aucorp=&rft.date=20120101&rft.volume=1&rft.issue=&rft.part=&rft.quarter=&rft.ssn=&rft.spage=73&rft.epage=82&rft.pages=73-82&rft.artnum=&rft.issn=&rft.eissn=&rft.isbn=9783540795674&rft.sici=&rft.coden=&rft_id=info:doi/10.1007/978-3-540-79567-4_2.1.1&rft.object_id=&rft.eisbn=&rft.edition=&rft.pub=Springer%20Berlin%20Heidelberg&rft.place=&rft.series=&rft.stitle=&rft.bici=&rft_id=info:bibcode/&rft_id=info:hdl/&rft_id=info:lccn/&rft_id=info:oclcnum/&rft_id=info:pmid/&rft_id=info:eric/((addata/eric}}&rft_dat=%3Cscopus%3E2-s2.0-84923867273%3C/scopus%3E,language=eng,view=UNSWS&svc_dat=single_service&env_type=test

==Overview of eye development==

=== Timeline of embryonic development ===

{| class="wikitable"
! style="background:#f4a941" | WEEK
! style="background:#f4a941" | DEVELOPMENT
|-
| 3-4 || Eye fields, Optic vesicles
|-
| 5-6 || Optic Cup, Lens Vesicle, Choroid Fissure, Hyaloid Artery
|-
| 7-8 || Cornea, Anterior Chamber, Pupillary Membrane, Lens, Retina
|-
| 8-10 || Eyelids
|-
| 9-15 || Iris, Ciliary Body
|}

=== Carnegie Stages ===

Carnegie Stages is a system of 23 stages used to describe developmental events of the vertebrate embryo. At stage 10 we see early signs related to eye development.

{| class="wikitable"
! style="background:#f4a941" | STAGE
! style="background:#f4a941" | EVENTS
|-
| Stage 10 (22 days) || The optic primordium has developed. Two small grooves develop on each side of the developing forebrain in the neural folds - this is the optic grooves. The optic placode has begun to develop, which is seen by a small thickening of the surface ectoderm lateral to the hindbrain.
|-
| Stage 11 (24 days) || Optic vesicle begins to form from the optic groove. Otic pit has formed.
|-
| Stage 12 (26 days) || The optic vesicles have extended from the forbrain to the surface ectoderm. The optic vesicle now lies close to the surface ectoderm.
|-
| Stage 13 (28 days) || The optic vesicle interacts with the surface ectoderm and will induce this ectoderm to form the lens placode, which is the precursor of the lens.
|-
| Stage 14 (32 days) || The lens placode is indented by the lens pit and may be cup-shaped.
|-
| Stage 15 (33 days) || The lens pit will close and form a circle that separates from the surface ectoderm and becomes the lens vesicle. The lens vesicle and optic cub lie close to the surface ectoderm, which creates a slight elevation in the region of the eye.
|-
| Stage 16 (37 days ) || First indication of the development of the eyelids.
|-
| Stage 17 (41 days) || Retinal pigment is visible. The eyes are still laterally places, but starts to take a more anterior position. The lower eyelid fold has begun to form.
|-
| Stage 18 (44 days) || Mesenchyme invades the region between the lens epithelium and the surface ectoderm. The eyes has shifted to more anterior position. The groove above and below the eyes are deeper, but have not joined yet. Eyelid folds develop.
|-
| Stage 19 (48 days) || The upper and the lower eyelids now meet at the outer canthus.
|-
| Stage 20 (51 days) || The lens cavity is lost. The upper and lower lids meet laterally and medially. The eyelids now partly cover the eye.
|-
| Stage 21 (52 days) ||
|-
| Stage 22 (54 days) ||
|-
| Stage 23 (57 days) || The face is beginning to look human.
|-
|}

=== Embryonic Contributions ===

The eyes are derived from four sources:

{| class="wikitable"
! style="background:#f4a941" | Embryonic contributions
! style="background:#f4a941" | Eye component
|-
| Neuroectoderm of the forebrain || Retina, Posterior layers of the iris, The optic nerve
|-
| Surface ectoderm of the head || The lens of the eye, The corneal epithelium
|-
| Mesoderm between the neuroectoderm and the surface ectoderm || The fibrous and vascular coats of the eye
|-
| Neural crest cells || Choroid, Sclera, Corneal endothelium
|}

=== Short overview ===

[[File:DevelopmentEye-PMC43029243.jpg|400px|thumb|right|'''Figure 1.''' Stages of lens formation in mouse embryos]]

The eye starts to develop at 22 days. The optic grooves (sulci) appears in the neural folds at the cranial end of the embryo. When the neural fold fuse to form the forebrain, the optic grooves will form optic vesicles. The optic vesicles are continuous cavities from the cavity of the forebrain and project from the wall of the forebrain and into the mesenchyme. The optic vesicle extends from the diencephalon and will come in contact with the surface ectoderm of the head. This induces the formation of a lens placode. The surface ectoderm near the optic vesicles will thicken and form the lens placodes. The lens placodes will sink into the surface ectoderm and form lens pits. The edges of the lens pits will travel towards each other and fuse to form round lens vesicles, which will later lose connection with the surface ectoderm. The optic vesicles do also keep developing - they will form double-walled optic cups which are connected to the brain by the optic stalk. The two layers of the optic cup will differentiate in different directions. The cells of the outer layer will produce melanin pigment and later become the pigmented retina. The cells of the inner layer of the optic cup will proliferate fast and develop glia, ganglion cells, interneurons and light-sensitive photoreceptor neurons. These cells are in the neural retina. The ganglion cells of the retina are neurons that send signal to the brain. The axons of the ganglion cells of the neural retina will grow in the wall of the optic stalk. The cavity in the optic nerve will start disappearing, and instead, the axons of the ganglion cells will form the '''optic nerve'''.
The optic stalk is now the optic nerve <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>

The optic cups will fold inwards around the lens while the lens vesicles have grown inwards so they have fully lost their connection with the surface ectoderm, which locates them in the cavities of the optic cups. The retinal fissures (linear grooves) will develop and cover the ventral surface of the optic cups and down to the optic stalk. The retinal fissures contain vascular mesenchyme and hyaloid blood vessels will develop here. The hyaloid artery supplies the structures in the eye with blood and the hyaloid vein will return the blood from these structures.

'''Formation of the optic vesicle'''

It is a specific area of the neural ectoderm that will become the optic vesicle - this happens because of a group of transcription factors - Six3, Pax6, and Rx1. These transcription factors are expressed in the most anterior tip of the neural plate. This area will split into bilateral regions and form the optic vesicles. The Pax6 protein has shown to be especially important for the development of the lens and retina. This protein is important for photoreceptive cells in all phyla. Pax 6 is also present in the murine forebrain, hindbrain, and nasal placodes, but the eyes are most sensitive its absence <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

The sonic hedgehog gene is important for the separation of the single eye field into two fields. If this gene is inhibited, the eye field will not split which will result in cyclopia, a single eye in the center of the face <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

== Development of the eye components ==

=== Lens ===

Human lens induction occurs at around 28 days and is completed around day 56. The surface ectoderm will thicken near the optic vesicle and create the lens placode and later form the lens vesicle <ref><pubmed>20171212 </pubmed></ref>. Lens cells come from ectoderm and differentiate into either lens fibers or the lens epithelium. The anterior monolayer of epithelial cells of the lens will create the lens epithelium, which makes the sheet of cuboidal epithelium covering the anterior surface of the lens. The posterior lens vesicle cells will produce the linear primary fibre cells aligned parallel to the optic axis. These fibres will create the lens mass and form the embryonic lens nucleus. The lens epithelial cells will keep proliferating and produce new cells which generate a secondary lens fiber cells. This rows of cell will form the outer shells and keep the lens growing throughout life. This makes the eye lens unique - it will have an addition of new cells inside the surrounding capsule all the time <ref><pubmed>25406393</pubmed></ref>.

=== Retina ===
5075778

=== Ciliary Body ===

The ciliary body is a muscular and secretory tissue and is located directly behind the lens. The ciliary body forms part of the anterior segment of the eye and is an important regulator of eye physiology and the vision. The ciliary body produces the aqueous fluid which fills the eyes and nourishes the lens and cornea - this aqueous fluid function to keep the eye in a pressurized and inflated state, which is important the vision.The ciliary body also synthesizes collagenIX and tenasin-C <ref><pubmed>17275804</pubmed></ref>.

The ciliary body extends from the iris root (anteriorly) to the ora serrata (posteriorly). It consist of ciliary muscles and ciliary processes. Each ciliary process (fold) is covered by a double-layered secretory epithelium; the outer pigmented and the inner unpigmented (closes to the lens). The epithelial layers of the ciliary body comes from the retina of the optic cup. We see two different ciliary body epithelium: the inner non-pigmented ciliary epithelium which is connected with the neural retina and the outer pigmented ciliary epithelium which is connected with the retinal pigmented epithelium. The epithelium of the iris is the further anterior extension. The epithelial layers are associated with a stroma containing the ciliary muscle. The ciliary muscle is complex, but can be divided into three portions; anterior, posterior and internal <ref><pubmed>12127103</pubmed></ref>.

In the chick eye development, we see the mesenchyme grow together on the margin of the optic cup and will form the stroma of the ciliary body and the iris, which is located more anteriorly. It is unknown how if the lens has a role in inducing the secretory ciliary body epithelium and the muscular iris epithelium <ref><pubmed>17275804</pubmed></ref>.

=== Iris ===

The Iris develops at the end of the third month of development. The iris is a thin layer and derives from the anterior rim of the optic cup. In the anterior of the eye, the optic epithelium is nonneural and matures as ciliary body and iris epithelia.

=== Cornea ===

http://www.sciencedirect.com/science/article/pii/S1877117315000642

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1298807/pdf/taos00013-0203.pdf

=== Aqueous Chambers ===
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=== Choroid and Sclera ===
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<ref><pubmed>23528534</pubmed></ref>

=== Eyelids ===

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=== Lacrimal Glands ===

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=== Extraocular muscles ===
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<pubmed>26410132</pubmed>
<pubmed>23071378</pubmed>

We could talk briefly in this sections about the causes of short/long-sightedness and common causes of blindness at a developmental level - z3416557

== Congenital Anomalies ==
We could talk briefly in this sections about the causes of short/long-sightedness and common causes of blindness at a developmental level - z3416557

Although quite rare, abnormalities can occur during the embryonic development that causes serious effects to the features of the eyes, its function as well as the further normal development after birth. These anomalies can occur unilaterally or bilaterally and it is also common for most reported cases to have more than one type of eye abnormalities at a time. Thus, the estimated prevalence statistics listed in the table can overlap.

{| class="wikitable"
! style="background:#f4a941" | Congenital Anomalies
! style="background:#f4a941" | Description
! style="background:#f4a941" | Epidemiology
|-
| Anopthalmia || The absence of the eyes.
| rowspan="2" | Prevalence: Anophthalmia-Microphthalmia Syndrome was estimated to be 5.3 per 100 000 cases <ref name="Orphanet Report Series - Rare Diseases Collection">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: http://www.orpha.net</ref>
|-
| Microphtalmia || Abnormal reduction in size of the eyeballs.
|-
| Coloboma || A condition where parts of the eye is missing and failed to develop normally.
| Prevalence: Occular coloboma was estimated to be 8.0 per 100 000 cases <ref name="Orphanet Report Series - Rare Diseases Collection">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: http://www.orpha.net</ref>
|-
| Aniridia || Complete or partial absence of the iris.
| Prevalence: Estimated to be 1.5 per 100 000 cases <ref name="Orphanet Report Series - Rare Diseases Collection">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: http://www.orpha.net</ref>
|-
| Optic Nerve Hypoplasia || A condition where the optic nerves are underdeveloped.
| Prevalence: Reported to be the most common abnormality <ref name="The Optic Nerve Hypoplasia">Ryabets-Lienhard, A., Stewart, C., Borchert, M., & Geffner, M. E. (2016). The Optic Nerve Hypoplasia Spectrum - Review of the Literature and Clinical Guidelines. ''Advances in Pediatrics, 63'', 127-146. doi: 10.1016/j.yapd.2016.04.009 </ref>
*10.9 per 100 000 in United Kingdom
*17.3 per 100 000 cases in Sweden.
*6.3% of cases was reported in New Zealand
|-
|}

[[File:Anophthalmia.jpeg|150px|thumb|left|'''Figure 2.''' Anopthalmia birth defect]]
[[File:Microphthalmia-500px.jpg|150px|thumb|centre|'''Figure 3.''' Microphthalmia birth defect]]

==Glossary==

==References==

<references/>

==External links==

z5075309 - <pubmed>26956898</pubmed>

2017 Group Project 4

2017-10-05T01:32:59Z

Z3416557: /* Introduction */

{{ANAT2341Project2017header}}

= Eye Development =
[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 16:09, 14 September 2017 (AEST) OK Feedback
* Timelines
* Embryonic contributions from germ layers and neural crest
* Cellular components
* Current research areas
* Get rid of the bold formatting for sub-headings.
* Animal models compared to human development
* Central neural pathway

== Anatomy of the Adult Eye ==

The eye is a complex sensory structure which allows a variety of species to intake and process visual information from the world around us.

To discuss the key anatomical components of the eye, we will break down the eye in parts:

Supporting Structures (Orbit, Extraoccular Muscles, Lacrimal Gland, Eyelid)

The orbit of the eye consists of a framework of bones and connective tissue which provide structural support and protection to the sensitive human eye. 7 bones contribute to the orbit of the eye: frontal, lacrimal, sphenoid, zygomtatic, ethmoid, maxilary, palatine. Several openings exist in the orbital structure, 2 key fissures are the superior orbital fissure and inferior orbital fissure and the posterior optic canal. These openings allow crainial nerves passageway.

A set of 6 extraoccular muscles allow for a strong voluntary control of the movement of the eye. These muscles include superior recuts, inferior rectus, lateral rectus, medial rectus, inferior oblique, superior oblique muscles. These muscles are some of the smallest in the human body and are designed to produce fast, controlled motion to focus on an object of interest.

The eyelid is the anterior covering of the eye, consisting of a thin fold of skin. It is controlled by the levitator palpabrae superioris muscle. Superio-laterally to the eyelid is the lacrimal gland, which serves to create a film of tear, an important component to keeping the anterior surface of the eye moist. The eyelid assists in this process by opening and closing, or blinking, which spreads the tear film across the surface of the eye. Tear film and debris caught in the tear film are excreted through the lacrimal duct which is located on the infero-medial surface of the eyelid.

Layers of the Eyeball (Sclera, Choroid, Retina)

The superficial layers of the eyeball is the sclera, a thick layer which becomes thicker as it extends posterior. The sclera is the visible in anatomical position as the white part of our eye. It's function is to provide structural stability to the eye and serves as attachment for some extraoccular insertions. Deep to the sclera is the choroid, a vascular network which provides nourishment to the layers of the eyeball and plays a large role in the growth of the eye. Deep to the choroid is the retina, a network of nerve fibers which transmit visual information. The retina contains 2 types of photoreceptors which convert visible light into nerve impulses. Rods work best in low light environments while cones work best in high light enthronements and detect colour and sharp detail.

Anterior structure (Lens, Cornea, Pupil, Iris, Ciliary Body)

Posterior structure (Optic Nerve, Optic Disc, Macula Lutea)

ref: https://ap01-a.alma.exlibrisgroup.com/view/uresolver/61UNSW_INST/openurl?ctx_enc=info:ofi/enc:UTF-8&ctx_id=10_1&ctx_tim=2017-09-07T14%3A11%3A09IST&ctx_ver=Z39.88-2004&url_ctx_fmt=info:ofi/fmt:kev:mtx:ctx&url_ver=Z39.88-2004&rfr_id=info:sid/primo.exlibrisgroup.com-scopus&req_id=&rft_val_fmt=info:ofi/fmt:kev:mtx:book&rft.genre=bookitem&rft.atitle=Anatomy%20of%20the%20eye&rft.jtitle=&rft.btitle=Handbook%20of%20Visual%20Display%20Technology&rft.aulast=Garhart&rft.auinit=C&rft.auinit1=&rft.auinitm=&rft.ausuffix=&rft.au=Garhart,%20C.&rft.aucorp=&rft.date=20120101&rft.volume=1&rft.issue=&rft.part=&rft.quarter=&rft.ssn=&rft.spage=73&rft.epage=82&rft.pages=73-82&rft.artnum=&rft.issn=&rft.eissn=&rft.isbn=9783540795674&rft.sici=&rft.coden=&rft_id=info:doi/10.1007/978-3-540-79567-4_2.1.1&rft.object_id=&rft.eisbn=&rft.edition=&rft.pub=Springer%20Berlin%20Heidelberg&rft.place=&rft.series=&rft.stitle=&rft.bici=&rft_id=info:bibcode/&rft_id=info:hdl/&rft_id=info:lccn/&rft_id=info:oclcnum/&rft_id=info:pmid/&rft_id=info:eric/((addata/eric}}&rft_dat=%3Cscopus%3E2-s2.0-84923867273%3C/scopus%3E,language=eng,view=UNSWS&svc_dat=single_service&env_type=test

==Overview of eye development==

=== Timeline of embryonic development ===

{| class="wikitable"
! style="background:#f4a941" | WEEK
! style="background:#f4a941" | DEVELOPMENT
|-
| 3-4 || Eye fields, Optic vesicles
|-
| 5-6 || Optic Cup, Lens Vesicle, Choroid Fissure, Hyaloid Artery
|-
| 7-8 || Cornea, Anterior Chamber, Pupillary Membrane, Lens, Retina
|-
| 8-10 || Eyelids
|-
| 9-15 || Iris, Ciliary Body
|}

=== Carnegie Stages ===

Carnegie Stages is a system of 23 stages used to describe developmental events of the vertebrate embryo. At stage 10 we see early signs related to eye development.

{| class="wikitable"
! style="background:#f4a941" | STAGE
! style="background:#f4a941" | EVENTS
|-
| Stage 10 (22 days) || The optic primordium has developed. Two small grooves develop on each side of the developing forebrain in the neural folds - this is the optic grooves. The optic placode has begun to develop, which is seen by a small thickening of the surface ectoderm lateral to the hindbrain.
|-
| Stage 11 (24 days) || Optic vesicle begins to form from the optic groove. Otic pit has formed.
|-
| Stage 12 (26 days) || The optic vesicles have extended from the forbrain to the surface ectoderm. The optic vesicle now lies close to the surface ectoderm.
|-
| Stage 13 (28 days) || The optic vesicle interacts with the surface ectoderm and will induce this ectoderm to form the lens placode, which is the precursor of the lens.
|-
| Stage 14 (32 days) || The lens placode is indented by the lens pit and may be cup-shaped.
|-
| Stage 15 (33 days) || The lens pit will close and form a circle that separates from the surface ectoderm and becomes the lens vesicle. The lens vesicle and optic cub lie close to the surface ectoderm, which creates a slight elevation in the region of the eye.
|-
| Stage 16 (37 days ) || First indication of the development of the eyelids.
|-
| Stage 17 (41 days) || Retinal pigment is visible. The eyes are still laterally places, but starts to take a more anterior position. The lower eyelid fold has begun to form.
|-
| Stage 18 (44 days) || Mesenchyme invades the region between the lens epithelium and the surface ectoderm. The eyes has shifted to more anterior position. The groove above and below the eyes are deeper, but have not joined yet. Eyelid folds develop.
|-
| Stage 19 (48 days) || The upper and the lower eyelids now meet at the outer canthus.
|-
| Stage 20 (51 days) || The lens cavity is lost. The upper and lower lids meet laterally and medially. The eyelids now partly cover the eye.
|-
| Stage 21 (52 days) ||
|-
| Stage 22 (54 days) ||
|-
| Stage 23 (57 days) || The face is beginning to look human.
|-
|}

=== Embryonic Contributions ===

The eyes are derived from four sources:

{| class="wikitable"
! style="background:#f4a941" | Embryonic contributions
! style="background:#f4a941" | Eye component
|-
| Neuroectoderm of the forebrain || Retina, Posterior layers of the iris, The optic nerve
|-
| Surface ectoderm of the head || The lens of the eye, The corneal epithelium
|-
| Mesoderm between the neuroectoderm and the surface ectoderm || The fibrous and vascular coats of the eye
|-
| Neural crest cells || Choroid, Sclera, Corneal endothelium
|}

=== Short overview ===

[[File:DevelopmentEye-PMC43029243.jpg|400px|thumb|right|'''Figure 1.''' Stages of lens formation in mouse embryos]]

The eye starts to develop at 22 days. The optic grooves (sulci) appears in the neural folds at the cranial end of the embryo. When the neural fold fuse to form the forebrain, the optic grooves will form optic vesicles. The optic vesicles are continuous cavities from the cavity of the forebrain and project from the wall of the forebrain and into the mesenchyme. The optic vesicle extends from the diencephalon and will come in contact with the surface ectoderm of the head. This induces the formation of a lens placode. The surface ectoderm near the optic vesicles will thicken and form the lens placodes. The lens placodes will sink into the surface ectoderm and form lens pits. The edges of the lens pits will travel towards each other and fuse to form round lens vesicles, which will later lose connection with the surface ectoderm. The optic vesicles do also keep developing - they will form double-walled optic cups which are connected to the brain by the optic stalk. The two layers of the optic cup will differentiate in different directions. The cells of the outer layer will produce melanin pigment and later become the pigmented retina. The cells of the inner layer of the optic cup will proliferate fast and develop glia, ganglion cells, interneurons and light-sensitive photoreceptor neurons. These cells are in the neural retina. The ganglion cells of the retina are neurons that send signal to the brain. The axons of the ganglion cells of the neural retina will grow in the wall of the optic stalk. The cavity in the optic nerve will start disappearing, and instead, the axons of the ganglion cells will form the '''optic nerve'''.
The optic stalk is now the optic nerve <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>

The optic cups will fold inwards around the lens while the lens vesicles have grown inwards so they have fully lost their connection with the surface ectoderm, which locates them in the cavities of the optic cups. The retinal fissures (linear grooves) will develop and cover the ventral surface of the optic cups and down to the optic stalk. The retinal fissures contain vascular mesenchyme and hyaloid blood vessels will develop here. The hyaloid artery supplies the structures in the eye with blood and the hyaloid vein will return the blood from these structures.

'''Formation of the optic vesicle'''

It is a specific area of the neural ectoderm that will become the optic vesicle - this happens because of a group of transcription factors - Six3, Pax6, and Rx1. These transcription factors are expressed in the most anterior tip of the neural plate. This area will split into bilateral regions and form the optic vesicles. The Pax6 protein has shown to be especially important for the development of the lens and retina. This protein is important for photoreceptive cells in all phyla. Pax 6 is also present in the murine forebrain, hindbrain, and nasal placodes, but the eyes are most sensitive its absence <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

The sonic hedgehog gene is important for the separation of the single eye field into two fields. If this gene is inhibited, the eye field will not split which will result in cyclopia, a single eye in the center of the face <ref name="DevelopmentalBiology">Gilbert SF. Developmental Biology. 6th edition. Sunderland (MA): Sinauer Associates; 2000. Available from: https://www.ncbi.nlm.nih.gov/books/NBK9983/</ref>.

== Development of the eye components ==

=== Lens ===

Human lens induction occurs at around 28 days and is completed around day 56. The surface ectoderm will thicken near the optic vesicle and create the lens placode and later form the lens vesicle <ref><pubmed>20171212 </pubmed></ref>. Lens cells come from ectoderm and differentiate into either lens fibers or the lens epithelium. The anterior monolayer of epithelial cells of the lens will create the lens epithelium, which makes the sheet of cuboidal epithelium covering the anterior surface of the lens. The posterior lens vesicle cells will produce the linear primary fibre cells aligned parallel to the optic axis. These fibres will create the lens mass and form the embryonic lens nucleus. The lens epithelial cells will keep proliferating and produce new cells which generate a secondary lens fiber cells. This rows of cell will form the outer shells and keep the lens growing throughout life. This makes the eye lens unique - it will have an addition of new cells inside the surrounding capsule all the time <ref><pubmed>25406393</pubmed></ref>.

=== Retina ===
5075778

=== Ciliary Body ===

The ciliary body is a muscular and secretory tissue and is located directly behind the lens. The ciliary body forms part of the anterior segment of the eye and is an important regulator of eye physiology and the vision. The ciliary body produces the aqueous fluid which fills the eyes and nourishes the lens and cornea - this aqueous fluid function to keep the eye in a pressurized and inflated state, which is important the vision.The ciliary body also synthesizes collagenIX and tenasin-C <ref><pubmed>17275804</pubmed></ref>.

The ciliary body extends from the iris root (anteriorly) to the ora serrata (posteriorly). It consist of ciliary muscles and ciliary processes. Each ciliary process (fold) is covered by a double-layered secretory epithelium; the outer pigmented and the inner unpigmented (closes to the lens). The epithelial layers of the ciliary body comes from the retina of the optic cup. We see two different ciliary body epithelium: the inner non-pigmented ciliary epithelium which is connected with the neural retina and the outer pigmented ciliary epithelium which is connected with the retinal pigmented epithelium. The epithelium of the iris is the further anterior extension. The epithelial layers are associated with a stroma containing the ciliary muscle. The ciliary muscle is complex, but can be divided into three portions; anterior, posterior and internal <ref><pubmed>12127103</pubmed></ref>.

In the chick eye development, we see the mesenchyme grow together on the margin of the optic cup and will form the stroma of the ciliary body and the iris, which is located more anteriorly. It is unknown how if the lens has a role in inducing the secretory ciliary body epithelium and the muscular iris epithelium <ref><pubmed>17275804</pubmed></ref>.

=== Iris ===

The Iris develops at the end of the third month of development. The iris is a thin layer and derives from the anterior rim of the optic cup. In the anterior of the eye, the optic epithelium is nonneural and matures as ciliary body and iris epithelia.

=== Cornea ===

http://www.sciencedirect.com/science/article/pii/S1877117315000642

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1298807/pdf/taos00013-0203.pdf

=== Aqueous Chambers ===
5075309

=== Choroid and Sclera ===
5075309

<ref><pubmed>23528534</pubmed></ref>

=== Eyelids ===

5075309

=== Lacrimal Glands ===

5075309

=== Extraocular muscles ===
5075778

<pubmed>26410132</pubmed>
<pubmed>23071378</pubmed>

We could talk briefly in this sections about the causes of short/long-sightedness and common causes of blindness at a developmental level - z3416557

== Congenital Anomalies ==
We could talk briefly in this sections about the causes of short/long-sightedness and common causes of blindness at a developmental level - z3416557

Although quite rare, abnormalities can occur during the embryonic development that causes serious effects to the features of the eyes, its function as well as the further normal development after birth. These anomalies can occur unilaterally or bilaterally and it is also common for most reported cases to have more than one type of eye abnormalities at a time. Thus, the estimated prevalence statistics listed in the table can overlap.

{| class="wikitable"
! style="background:#f4a941" | Congenital Anomalies
! style="background:#f4a941" | Description
! style="background:#f4a941" | Epidemiology
|-
| Anopthalmia || The absence of the eyes.
| rowspan="2" | Prevalence: Anophthalmia-Microphthalmia Syndrome was estimated to be 5.3 per 100 000 cases <ref name="Orphanet Report Series - Rare Diseases Collection">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: http://www.orpha.net</ref>
|-
| Microphtalmia || Abnormal reduction in size of the eyeballs.
|-
| Coloboma || A condition where parts of the eye is missing and failed to develop normally.
| Prevalence: Occular coloboma was estimated to be 8.0 per 100 000 cases <ref name="Orphanet Report Series - Rare Diseases Collection">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: http://www.orpha.net</ref>
|-
| Aniridia || Complete or partial absence of the iris.
| Prevalence: Estimated to be 1.5 per 100 000 cases <ref name="Orphanet Report Series - Rare Diseases Collection">Orphanet Report Series – Rare Diseases Collection. (2017). ''Prevalence of rare diseases: Bibliographic data (no. 2). Paris''. France: Author. Retrieved from: http://www.orpha.net</ref>
|-
| Optic Nerve Hypoplasia || A condition where the optic nerves are underdeveloped.
| Prevalence: Reported to be the most common abnormality <ref name="The Optic Nerve Hypoplasia">Ryabets-Lienhard, A., Stewart, C., Borchert, M., & Geffner, M. E. (2016). The Optic Nerve Hypoplasia Spectrum - Review of the Literature and Clinical Guidelines. ''Advances in Pediatrics, 63'', 127-146. doi: 10.1016/j.yapd.2016.04.009 </ref>
*10.9 per 100 000 in United Kingdom
*17.3 per 100 000 cases in Sweden.
*6.3% of cases was reported in New Zealand
|-
|}

[[File:Anophthalmia.jpeg|150px|thumb|left|'''Figure 2.''' Anopthalmia birth defect]]
[[File:Microphthalmia-500px.jpg|150px|thumb|centre|'''Figure 3.''' Microphthalmia birth defect]]

==Glossary==

==References==

<references/>

==External links==

z5075309 - <pubmed>26956898</pubmed>

2017 Group Project 4

2017-09-14T03:38:40Z

Z3416557: /* Anatomy of the eye */

{{ANAT2341Project2017header}}

= Anatomy of the Eye =

The eye is a complex sensory structure which allows a variety of species to intake and process visual information from the world around us.

To discuss the key anatomical components of the eye, we will break down the eye functionally:

Supporting Structures (Orbit, Extraoccular Muscles, Lacrimal Gland)

The orbit of the eye consists of a framework of bones and connective tissue which provide structural support and protection to the sensitive human eye. 7 bones contribute to the orbit of the eye: frontal, lacrimal, sphenoid, zygomtatic, ethmoid, maxilary, palatine. Several openings exist in the orbital structure, 2 key fissures are the superior orbital fissure and inferior orbital fissure and the posterior optic canal. These openings allow crainial nerves passageway.

A set of 6 extraoccular muscles allow for a strong voluntary control of the movement of the eye. These muscles include superior recuts, inferior rectus, lateral rectus, medial rectus, inferior oblique, superior oblique muscles. These muscles are some of the smallest in the human body and are designed to produce fast, controlled motion to focus on an object of interest.

The eyelid is the anterior covering of the eye, consisting of a thin fold of skin. It is controlled by the levitator palpabrae superioris muscle. Superio-laterally to the eyelid is the lacrimal gland, which serve to create a film of tear, an important component to keeping the anterior surface of the eye moist. The eyelid assists in this process by opening and closing, or blinking, which spreads the tear film across the surface of the eye. Tear film and debris caught in the tear film are excreted through the lacrimla duct which is located on the infero-medial surface of the eyelid.

Anterior structure

ref: https://ap01-a.alma.exlibrisgroup.com/view/uresolver/61UNSW_INST/openurl?ctx_enc=info:ofi/enc:UTF-8&ctx_id=10_1&ctx_tim=2017-09-07T14%3A11%3A09IST&ctx_ver=Z39.88-2004&url_ctx_fmt=info:ofi/fmt:kev:mtx:ctx&url_ver=Z39.88-2004&rfr_id=info:sid/primo.exlibrisgroup.com-scopus&req_id=&rft_val_fmt=info:ofi/fmt:kev:mtx:book&rft.genre=bookitem&rft.atitle=Anatomy%20of%20the%20eye&rft.jtitle=&rft.btitle=Handbook%20of%20Visual%20Display%20Technology&rft.aulast=Garhart&rft.auinit=C&rft.auinit1=&rft.auinitm=&rft.ausuffix=&rft.au=Garhart,%20C.&rft.aucorp=&rft.date=20120101&rft.volume=1&rft.issue=&rft.part=&rft.quarter=&rft.ssn=&rft.spage=73&rft.epage=82&rft.pages=73-82&rft.artnum=&rft.issn=&rft.eissn=&rft.isbn=9783540795674&rft.sici=&rft.coden=&rft_id=info:doi/10.1007/978-3-540-79567-4_2.1.1&rft.object_id=&rft.eisbn=&rft.edition=&rft.pub=Springer%20Berlin%20Heidelberg&rft.place=&rft.series=&rft.stitle=&rft.bici=&rft_id=info:bibcode/&rft_id=info:hdl/&rft_id=info:lccn/&rft_id=info:oclcnum/&rft_id=info:pmid/&rft_id=info:eric/((addata/eric}}&rft_dat=%3Cscopus%3E2-s2.0-84923867273%3C/scopus%3E,language=eng,view=UNSWS&svc_dat=single_service&env_type=test

=Eye Development=

== Timeline ==

'''Week 3 - 4'''
* Optic vesicles
* Lens placode

'''Week 5 - 6'''
* Optic cup
* Lens vesicle
* Hyaloid artery

'''Week 7 - 8'''
* Cornea
* Anterior Chamber
* Lens
* Retina

'''Week 9 - 15'''
* Iris
* Cillary Body

'''Week 8 - 10'''
* Eyelids

== Carnegie Stages ==

== Development of the eye components ==

The eyes are derived from four sources:

* The neuroectoderm of the forebrain forms
** Retina
** Posterior layers of the iris
** The optic nerve.
* The surface ectoderm of the head forms
** The lens of the eye
** The corneal epithelium.
* The mesoderm between the neuroectoderm and the surface ectoderm forms
** The fibrous and vascular coats of the eye
* The neural crest cells forms
** Choroid
** Sclera
** Corneal endothelium

'''Overview of eye development'''

The eye starts to develop at 22 days. The optic grooves (sulci) appears in the neural folds at the cranial end of the embryo. When the neural fold fuse to form the forebrain, the optic grooves will form optic vesicles. The optic vesicles are continuous cavities from the cavity of the forebrain and project from the wall of the forebrain and into the mesenchyme. The optic vesicle extends from the diencephalon and will come in contact with the surface ectoderm of the head. This induces the formation of a lens placode. The surface ectoderm near the optic vesicles will thicken and form the lens placodes. The lens placodes will sink into the surface ectoderm and form lens pits. The edges of the lens pits will travel towards each other and fuse to form round lens vesicles, which will later lose connection with the surface ectoderm. The optic vesicles do also keep developing - they will form double-walled optic cups which are connected to the brain by the optic stalk. The two layers of the optic cup will differentiate in different directions. The cells of the outer layer will produce melanin pigment and later become the pigmented retina. The cells of the inner layer of the optic cup will proliferate fast and develop glia, ganglion cells, interneurons and light-sensitive photoreceptor neurons. These cells are in the neural retina. The ganglion cells of the retina are neurons that send signal to the brain. The axons of the ganglion cells of the neural retina will grow in the wall of the optic stalk. The cavity in the optic nerve will start disappearing, and instead, the axons of the ganglion cells will form the '''optic nerve'''.
The optic stalk is now the optic nerve <ref>https://www.ncbi.nlm.nih.gov/books/NBK10024/#</ref>

The optic cups will fold inwards around the lens while the lens vesicles have grown inwards so they have fully lost their connection with the surface ectoderm, which locates them in the cavities of the optic cups. The retinal fissures (linear grooves) will develop and cover the ventral surface of the optic cups and down to the optic stalk. The retinal fissures contain vascular mesenchyme and hyaloid blood vessels will develop here. The hyaloid artery supplies the structures in the eye with blood and the hyaloid vein will return the blood from these structures.

'''Formation of the optic vesicle'''

It is a specific area of the neural ectoderm that will become the optic vesicle - this happens because of a group of transcription factors - Six3, Pax6, and Rx1. These transcription factors are expressed in the most anterior tip of the neural plate. This area will split into bilateral regions and form the optic vesicles. The Pax6 protein has shown to be especially important for the development of the lens and retina. This protein is important for photoreceptive cells in all phyla. Pax 6 is also present in the murine forebrain, hindbrain, and nasal placodes, but the eyes are most sensitive its absence <ref>https://www.ncbi.nlm.nih.gov/books/NBK10024/#</ref>.

The sonic hedgehog gene is important for the separation of the single eye field into two fields. If this gene is inhibited, the eye field will not split which will result in cyclopia, a single eye in the center of the face <ref>https://www.ncbi.nlm.nih.gov/books/NBK10024/#</ref>.

===== '''Lens''' =====

Human lens induction occurs at around 28 days and is completed around day 56. The surface ectoderm will thicken near the optic vesicle and create the lens placode and later form the lens vesicle <ref><pubmed>20171212 </pubmed></ref>. Lens cells come from ectoderm and differentiate into either lens fibers or the lens epithelium. The anterior monolayer of epithelial cells of the lens will create the lens epithelium, which makes the sheet of cuboidal epithelium covering the anterior surface of the lens. The posterior lens vesicle cells will produce the linear primary fibre cells aligned parallel to the optic axis. These fibres will create the lens mass and form the embryonic lens nucleus. The lens epithelial cells will keep proliferating and produce new cells which generate a secondary lens fiber cells. This rows of cell will form the outer shells and keep the lens growing throughout life. This makes the eye lens unique - it will have an addition of new cells inside the surrounding capsule all the time <ref><pubmed>25406393</pubmed></ref>.

===== '''Retina''' =====
5075778

====='''Ciliary Body'''=====

The ciliary body is a muscular and secretory tissue and is located directly behind the lens. The ciliary body forms part of the anterior segment of the eye and is an important regulator of eye physiology and the vision. The ciliary body produces the aqueous fluid which fills the eyes and nourishes the lens and cornea - this aqueous fluid function to keep the eye in a pressurized and inflated state, which is important the vision.The ciliary body also synthesizes collagenIX and tenasin-C <ref><pubmed>17275804</pubmed></ref>.

The ciliary body extends from the iris root (anteriorly) to the ora serrata (posteriorly). It consist of ciliary muscles and ciliary processes. Each ciliary process (fold) is covered by a double-layered secretory epithelium; the outer pigmented and the inner unpigmented (closes to the lens). The epithelial layers of the ciliary body comes from the retina of the optic cup. We see two different ciliary body epithelium: the inner non-pigmented ciliary epithelium which is connected with the neural retina and the outer pigmented ciliary epithelium which is connected with the retinal pigmented epithelium. The epithelium of the iris is the further anterior extension. The epithelial layers are associated with a stroma containing the ciliary muscle. The ciliary muscle is complex, but can be divided into three portions; anterior, posterior and internal <ref><pubmed>12127103</pubmed></ref>.

In the chick eye development, we see the mesenchyme grow together on the margin of the optic cup and will form the stroma of the ciliary body and the iris, which is located more anteriorly. It is unknown how if the lens has a role in inducing the secretory ciliary body epithelium and the muscular iris epithelium <ref><pubmed>17275804</pubmed></ref>.

====='''Iris'''=====

The Iris develops at the end of the third month of development. The iris is a thin layer and derives from the anterior rim of the optic cup. In the anterior of the eye, the optic epithelium is nonneural and matures as ciliary body and iris epithelia.

z5177670

===== '''Cornea''' =====

z5177670

http://www.sciencedirect.com/science/article/pii/S1877117315000642

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1298807/pdf/taos00013-0203.pdf

===== '''Aqueous Chambers''' =====
5075309

===== '''Choroid and Sclera''' =====
5075309

<ref><pubmed>23528534</pubmed></ref>

===== '''Eyelids''' =====

5075309

====='''Lacrimal Glands'''=====

5075309

===== '''Extraocular muscles''' =====
5075778

<pubmed>26410132</pubmed>
<pubmed>23071378</pubmed>

== Common Abnormalities ==

We could talk briefly in this sections about the causes of short/long-sightedness and common causes of blindness at a developmental level - z3416557

== Further Research ==
5117343
In the news, media, websites starting point:
Macular Research: https://www.cera.org.au/research/macular-research/
> Bionic Eye - https://theconversation.com/artificial-vision-what-people-with-bionic-eyes-see-79758
Corneal Research: https://www.cera.org.au/research/corneal-research/

 '''Kertoconus'''
 http://www.eyedefectsresearch.org/research-grants.html
 '''Retinopathy of prematurity (ROP)'''
 http://www.rnib.org.uk/eye-health-eye-conditions-z-eye-conditions/retinopathy-prematurity
 '''Retinoblastoma'''
 https://www.cancer.org/cancer/retinoblastoma/about/new-research.html
 '''Retinochoroidal colomba'''
 https://rarediseases.info.nih.gov/diseases/1432/retinochoroidal-coloboma
 http://macs.org.uk/
 '''Optic Nerve Hypoplasia'''
 https://www.cafamily.org.uk/medical-information/conditions/o/optic-nerve-hypoplasia/
 '''Amblyopia'''
 https://www.rpbusa.org/rpb/resources-and-advocacy/resources/rpb-vision-resources/amblyopia-and-strabismus/
 '''Astigmatism'''
 www.nei.nih.gov/health/errors/astigmatism.asp
 '''Strabismus'''
 

==Glossary==

==References==

<references/>

==External links==

z5075309 - <pubmed>26956898</pubmed>

2017 Group Project 4

2017-09-07T06:37:45Z

Z3416557: /* Introduction to the eye */

{{ANAT2341Project2017header}}

=Eye Development=

== Introduction to the eye ==

The eye is a complex structure which allows a variety of species to intake and process visual information from the world around us.

In humans the wall of the eye has 3 basic layers:
- An '''outer fibrous layer''' containing the posterior '''sclera''' and anterior '''cornea'''. The sclera ---
- A '''vascular middle layer''' containing the '''choroid'''
- An '''inner receptive layer''' containing the '''retina'''

Anterior structure

ref: https://ap01-a.alma.exlibrisgroup.com/view/uresolver/61UNSW_INST/openurl?ctx_enc=info:ofi/enc:UTF-8&ctx_id=10_1&ctx_tim=2017-09-07T14%3A11%3A09IST&ctx_ver=Z39.88-2004&url_ctx_fmt=info:ofi/fmt:kev:mtx:ctx&url_ver=Z39.88-2004&rfr_id=info:sid/primo.exlibrisgroup.com-scopus&req_id=&rft_val_fmt=info:ofi/fmt:kev:mtx:book&rft.genre=bookitem&rft.atitle=Anatomy%20of%20the%20eye&rft.jtitle=&rft.btitle=Handbook%20of%20Visual%20Display%20Technology&rft.aulast=Garhart&rft.auinit=C&rft.auinit1=&rft.auinitm=&rft.ausuffix=&rft.au=Garhart,%20C.&rft.aucorp=&rft.date=20120101&rft.volume=1&rft.issue=&rft.part=&rft.quarter=&rft.ssn=&rft.spage=73&rft.epage=82&rft.pages=73-82&rft.artnum=&rft.issn=&rft.eissn=&rft.isbn=9783540795674&rft.sici=&rft.coden=&rft_id=info:doi/10.1007/978-3-540-79567-4_2.1.1&rft.object_id=&rft.eisbn=&rft.edition=&rft.pub=Springer%20Berlin%20Heidelberg&rft.place=&rft.series=&rft.stitle=&rft.bici=&rft_id=info:bibcode/&rft_id=info:hdl/&rft_id=info:lccn/&rft_id=info:oclcnum/&rft_id=info:pmid/&rft_id=info:eric/((addata/eric}}&rft_dat=%3Cscopus%3E2-s2.0-84923867273%3C/scopus%3E,language=eng,view=UNSWS&svc_dat=single_service&env_type=test

== Timeline of Eye Development ==

== Development of the eye components ==

The eyes are derived from four sources:

* The neuroectoderm of the forebrain forms
** Retina
** Posterior layers of the iris
** The optic nerve.
* The surface ectoderm of the head forms
** The lens of the eye
** The corneal epithelium.
* The mesoderm between the neuroectoderm and the surface ectoderm forms
** The fibrous and vascular coats of the eye
* The neural crest cells forms
** Choroid
** Sclera
** Corneal endothelium

INSERT PICTURE
The eye starts to develop at 22 days. The optic grooves (sulci) appears in the neural folds at the cranial end of the embryo. When the neural fold fuse to form the forebrain, the optic grooves will form optic vesicles. The optic vesicles are continuous cavities from the cavity of the forebrain and project from the wall of the forebrain and into the mesenchyme. The optic vesicles will grow and the optic stalks will form to keep the connection between the optic vesicles and the forebrain. The optic vesicles will at some point come in contact with the surface ectoderm and at the same time, the surface ectoderm near the optic vesicles will thicken and form the lens placodes. The lens placodes will sink into the surface ectoderm and form lens pits. The edges of the lens pits will travel towards each other and fuse to form round lens vesicles, which will later lose connection with the surface ectoderm. The optic vesicles do also keep developing - they will form double-walled optic cups which are connected to the brain by the optic stalk. The optic cups will form the retina and the optic stalk will form the optic nerve. The optic cups will fold inwards around the lens while the lens vesicles have grown inwards so they have fully lost their connection with the surface ectoderm, which locates them in the cavities of the optic cups. The retinal fissures (linear grooves) will develop and cover the ventral surface of the optic cups and down to the optic stalk. The retinal fissures contain vascular mesenchyme and hyaloid blood vessels will develop here. The hyaloid artery supplies the structures in the eye with blood and the hyaloid vein will return the blood from these structures.

http://www.annualreviews.org/doi/full/10.1146/annurev.cellbio.17.1.255?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed

===== '''Retina''' =====
5075778

===== '''Optic Nerve''' =====
z5177670

The axons of the ganglion cells of the neural retina will grow in the wall of the optic nerve. The cavity in the optic nerve will start disappearing, and instead, the axons of the ganglion cells will form the optic nerve.

====='''Ciliary Body'''=====
z5177670

====='''Iris'''=====
z5177670

===== '''Lens''' =====
z5177670

===== '''Aquous Chambers''' =====
5075309

===== '''Cornea''' =====

z5177670

===== '''Choroid and Sclera''' =====
5075309

<ref><pubmed>23528534</pubmed></ref>

===== '''Eyelids''' =====

5075309

====='''Lacrimal Glands'''=====

5075309

===== '''Extraocular muscles''' =====
5075778

<pubmed>26410132</pubmed>
<pubmed>23071378</pubmed>

== Common Abnormalities ==

We could talk briefly in this sections about the causes of short/long-sightedness and common causes of blindness at a developmental level - z3416557

== Further Research ==
5117343
In the news, media, websites starting point:
Macular Research: https://www.cera.org.au/research/macular-research/
> Bionic Eye - https://theconversation.com/artificial-vision-what-people-with-bionic-eyes-see-79758
Corneal Research: https://www.cera.org.au/research/corneal-research/
> Stem cells, corneal transplant
Cellular Reprogramming: https://www.cera.org.au/cellular-reprogramming/
Glaucoma Research: https://www.cera.org.au/research/glaucoma-research/

==Glossary==

==References==

<references/>

==Recent papers==
[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 10:15, 14 August 2017 (AEST) OK Group 4 below are some starting places.

<pubmed limit=5>Eye+Development</pubmed>

Here is a few papers talking about eye development

z5177670 - Eye Development and Retinogenesis (NCBI): [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3504437/ NCBI]

z5177670 - <pubmed>1100417</pubmed>

z5177670 - <pubmed>10627820</pubmed>

z5075309 - <pubmed>26956898</pubmed>

==External links==

{{Vision Links}}

PubMed Searches: [http://www.ncbi.nlm.nih.gov/pubmed?term=Eye+Development ''Eye Development''] | [http://www.ncbi.nlm.nih.gov/pubmed?term=Vision+Development ''Vision Development'']

BMC Dev Biol Search: [http://www.biomedcentral.com/bmcdevbiol/search/results?terms=Eye+Development ''Eye Development'']

2017 Group Project 4

2017-09-07T06:37:05Z

Z3416557: /* Introduction to the eye */

{{ANAT2341Project2017header}}

=Eye Development=

== Introduction to the eye ==

The eye is a complex structure which allows a variety of species to intake and process visual information from the world around us.

In humans the wall of the eye has 3 basic layers:
- An '''outer fibrous layer''' containing the posterior '''sclera''' and anterior '''cornea'''. The sclera ---
- A '''vascular middle layer''' containing the '''choroid'''
- An '''inner receptive layer''' containing the '''retina'''

Anterior structure

== Timeline of Eye Development ==

== Development of the eye components ==

The eyes are derived from four sources:

* The neuroectoderm of the forebrain forms
** Retina
** Posterior layers of the iris
** The optic nerve.
* The surface ectoderm of the head forms
** The lens of the eye
** The corneal epithelium.
* The mesoderm between the neuroectoderm and the surface ectoderm forms
** The fibrous and vascular coats of the eye
* The neural crest cells forms
** Choroid
** Sclera
** Corneal endothelium

INSERT PICTURE
The eye starts to develop at 22 days. The optic grooves (sulci) appears in the neural folds at the cranial end of the embryo. When the neural fold fuse to form the forebrain, the optic grooves will form optic vesicles. The optic vesicles are continuous cavities from the cavity of the forebrain and project from the wall of the forebrain and into the mesenchyme. The optic vesicles will grow and the optic stalks will form to keep the connection between the optic vesicles and the forebrain. The optic vesicles will at some point come in contact with the surface ectoderm and at the same time, the surface ectoderm near the optic vesicles will thicken and form the lens placodes. The lens placodes will sink into the surface ectoderm and form lens pits. The edges of the lens pits will travel towards each other and fuse to form round lens vesicles, which will later lose connection with the surface ectoderm. The optic vesicles do also keep developing - they will form double-walled optic cups which are connected to the brain by the optic stalk. The optic cups will form the retina and the optic stalk will form the optic nerve. The optic cups will fold inwards around the lens while the lens vesicles have grown inwards so they have fully lost their connection with the surface ectoderm, which locates them in the cavities of the optic cups. The retinal fissures (linear grooves) will develop and cover the ventral surface of the optic cups and down to the optic stalk. The retinal fissures contain vascular mesenchyme and hyaloid blood vessels will develop here. The hyaloid artery supplies the structures in the eye with blood and the hyaloid vein will return the blood from these structures.

http://www.annualreviews.org/doi/full/10.1146/annurev.cellbio.17.1.255?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub%3Dpubmed

===== '''Retina''' =====
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===== '''Optic Nerve''' =====
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The axons of the ganglion cells of the neural retina will grow in the wall of the optic nerve. The cavity in the optic nerve will start disappearing, and instead, the axons of the ganglion cells will form the optic nerve.

====='''Ciliary Body'''=====
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====='''Iris'''=====
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===== '''Lens''' =====
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===== '''Aquous Chambers''' =====
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===== '''Cornea''' =====

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===== '''Choroid and Sclera''' =====
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<ref><pubmed>23528534</pubmed></ref>

===== '''Eyelids''' =====

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====='''Lacrimal Glands'''=====

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===== '''Extraocular muscles''' =====
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<pubmed>26410132</pubmed>
<pubmed>23071378</pubmed>

== Common Abnormalities ==

We could talk briefly in this sections about the causes of short/long-sightedness and common causes of blindness at a developmental level - z3416557

== Further Research ==
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In the news, media, websites starting point:
Macular Research: https://www.cera.org.au/research/macular-research/
> Bionic Eye - https://theconversation.com/artificial-vision-what-people-with-bionic-eyes-see-79758
Corneal Research: https://www.cera.org.au/research/corneal-research/
> Stem cells, corneal transplant
Cellular Reprogramming: https://www.cera.org.au/cellular-reprogramming/
Glaucoma Research: https://www.cera.org.au/research/glaucoma-research/

==Glossary==

==References==

<references/>

==Recent papers==
[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 10:15, 14 August 2017 (AEST) OK Group 4 below are some starting places.

<pubmed limit=5>Eye+Development</pubmed>

Here is a few papers talking about eye development

z5177670 - Eye Development and Retinogenesis (NCBI): [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3504437/ NCBI]

z5177670 - <pubmed>1100417</pubmed>

z5177670 - <pubmed>10627820</pubmed>

z5075309 - <pubmed>26956898</pubmed>

==External links==

{{Vision Links}}

PubMed Searches: [http://www.ncbi.nlm.nih.gov/pubmed?term=Eye+Development ''Eye Development''] | [http://www.ncbi.nlm.nih.gov/pubmed?term=Vision+Development ''Vision Development'']

BMC Dev Biol Search: [http://www.biomedcentral.com/bmcdevbiol/search/results?terms=Eye+Development ''Eye Development'']

2017 Group Project 4

2017-08-31T02:25:53Z

Z3416557: /* Eye Development */

{{ANAT2341Project2017header}}

=Eye Development=

==Introduction to the eye==

Here we can give a short introduction to the eye. Just like a basic understanding :-)

We could give a description of the adult anatomy of the eye in this section - happy to take this as we've just covered this section in anatomy! - z3416557

==Development and function of components in the eye==

===== Optic Nerve =====

===== Retina =====
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===== Lens, ciliary body, iris =====
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===== Cornea =====
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===== Chambers of the eye and humors =====

===== Sclera, choroid =====

===== Eyelids and associated glands =====

===== Extraocular muscles =====

===== Common Abnormalities =====

We could talk briefly in this sections about the causes of short/long-sightedness and common causes of blindness at a developmental level - z3416557
==Glossary==

==References==

<references/>

==Recent papers==
[[User:Z8600021|Mark Hill]] ([[User talk:Z8600021|talk]]) 10:15, 14 August 2017 (AEST) OK Group 4 below are some starting places.

<pubmed limit=5>Eye+Development</pubmed>

Here is a few papers talking about eye development

z5177670 - Eye Development and Retinogenesis (NCBI): [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3504437/ NCBI]

z5177670 - <pubmed>1100417</pubmed>

z5177670 - <pubmed>10627820</pubmed>

z5075309 - <pubmed>26956898</pubmed>

==External links==

{{Vision Links}}

PubMed Searches: [http://www.ncbi.nlm.nih.gov/pubmed?term=Eye+Development ''Eye Development''] | [http://www.ncbi.nlm.nih.gov/pubmed?term=Vision+Development ''Vision Development'']

BMC Dev Biol Search: [http://www.biomedcentral.com/bmcdevbiol/search/results?terms=Eye+Development ''Eye Development'']

2017 Group Project 4

2017-08-10T06:59:13Z

Z3416557:

{{ANAT2341Project2017header}}

We have chosen to do the eye

User:Z3416557

2017-08-10T06:45:52Z

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2017-08-10T06:43:40Z

Z3416557:

{{ANAT2341ProjectGroup2017table}}

[[File:Chicken embryo E-cad and P-cad gastrulation.png|500px]]

Here is the [[Student Page]] demonstration page I showed in the Practical class.

Use this page to practice editing and don't forget to add a topic to the [[2017 Group Project 4]] page.

 
{{2017ANAT2341 footer}}

[[Student Page]]

User:Z3416557

2017-08-10T06:43:03Z

Z3416557:

{{ANAT2341ProjectGroup2017table}}

[[:File:HHstage4.jpg|7]]

Here is the [[Student Page]] demonstration page I showed in the Practical class.

Use this page to practice editing and don't forget to add a topic to the [[2017 Group Project 4]] page.

 
{{2017ANAT2341 footer}}

[[Student Page]]

User:Z3416557

2017-08-10T06:42:19Z

Z3416557:

{{ANAT2341ProjectGroup2017table}}

Here is the [[Student Page]] demonstration page I showed in the Practical class.

Use this page to practice editing and don't forget to add a topic to the [[2017 Group Project 4]] page.

 
{{2017ANAT2341 footer}}

[[Student Page]]

User:Z3416557

2017-08-10T06:42:03Z

Z3416557:

{{ANAT2341ProjectGroup2017table}}

[Chicken_embryo_E-cad_and_P-cad_gastrulation.png]

Here is the [[Student Page]] demonstration page I showed in the Practical class.

Use this page to practice editing and don't forget to add a topic to the [[2017 Group Project 4]] page.

 
{{2017ANAT2341 footer}}

[[Student Page]]

User:Z3416557

2017-08-10T06:41:51Z

Z3416557:

{{ANAT2341ProjectGroup2017table}}

Chicken_embryo_E-cad_and_P-cad_gastrulation.png

Here is the [[Student Page]] demonstration page I showed in the Practical class.

Use this page to practice editing and don't forget to add a topic to the [[2017 Group Project 4]] page.

 
{{2017ANAT2341 footer}}

[[Student Page]]

User:Z3416557

2017-08-10T06:34:07Z

Z3416557:

User:Z3416557

2017-08-10T06:33:52Z

Z3416557: