Vision - Cornea Development
|Embryology - 17 Dec 2017 Expand to Translate|
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- 1 Introduction
- 2 Some Recent Findings
- 3 Human Cornea
- 4 Cornea Epithelia
- 5 Carnegie Stages - Eye
- 6 Descemet Membrane
- 7 Mouse Cornea
- 8 Frog Cornea
- 9 Molecular
- 10 Additional Images
- 11 References
- 12 Terms
- 13 External Links
- 14 Glossary Links
These notes introduce the development of the cornea of the eye. The adult cornea has three layers: an outer epithelium layer (ectoderm), a middle stromal layer of collagen-rich extracellular matrix between stromal keratocytes (neural crest) and an inner layer of endothelial cells (neural crest).
The cornea is a vision-specific specialised sensory epithelia that in humans differentiates mainly in the postnatal period. It arises initially from cranial ectoderm adjacent to the lens placode and forms a presumptive corneal epithelium. Later neural crest cells migrate between the lens and presumptive structure to form both the corneal endothelium and the stromal fibroblasts (keratocytes). Neural crest development in humans, reptiles and birds differs from that seen in rodents, cats, rabbits, and cattle.
Some Recent Findings
|More recent papers|
This table shows an automated computer PubMed search using the listed sub-heading term.
References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.
Matthew Lovatt, Gary Hin-Fai Yam, Gary S Peh, Alan Colman, N Ray Dunn, Jodhbir S Mehta Directed differentiation of periocular mesenchyme from human embryonic stem cells. Differentiation: 2017; PubMed 29239730
Matheus Porto Sticca, Linda C Carrijo-Carvalho, Isa M B Silva, Luiz A Vieira, Luciene B Souza, Rubens Belfort Junior, Fábio Ramos S Carvalho, Denise Freitas Acanthamoeba keratitis in patients wearing scleral contact lenses. Cont Lens Anterior Eye: 2017; PubMed 29221710
Meiyan Li, Dong Yang, Yingjun Chen, Meng Li, Tian Han, Xingtao Zhou, Katherine Ni Late-onset diffuse lamellar keratitis 4 years after femtosecond laser-assisted small incision lenticule extraction: a case report. BMC Ophthalmol: 2017, 17(1);244 PubMed 29216872
Mark J Mannis, Jennifer J Ling, Ralph Kyrillos, Melissa Barnett Keratoconus and Personality-A Review. Cornea: 2017; PubMed 29215397
Rakesh K Raghupathy, Xun Zhang, Fei Liu, Reem H Alhasani, Lincoln Biswas, Saeed Akhtar, Luyuan Pan, Cecilia B Moens, Wenchang Li, Mugen Liu, Breandan N Kennedy, Xinhua Shu Rpgrip1 is required for rod outer segment development and ciliary protein trafficking in zebrafish. Sci Rep: 2017, 7(1);16881 PubMed 29203866
S Altan, H Sağsöz, Z Oğurtan Topical dimethyl sulfoxide inhibits corneal neovascularization and stimulates corneal repair in rabbits following acid burn. Biotech Histochem: 2017;1-18 PubMed 29233043
Megan R Silas, Sarah M Hilkert, James J Reidy, Asim V Farooq Posterior keratoconus. Br J Ophthalmol: 2017; PubMed 29122822
Özlem Barut Selver, Ayşe Yağcı, Sait Eğrilmez, Mehmet Gürdal, Melis Palamar, Türker Çavuşoğlu, Utku Ateş, Ali Veral, Çağrı Güven, Jose Mario Wolosin Limbal Stem Cell Deficiency and Treatment with Stem Cell Transplantation. Turk J Ophthalmol: 2017, 47(5);285-291 PubMed 29109898
Eric Weh, Hideyuki Takeuchi, Sanaa Muheisen, Robert S Haltiwanger, Elena V Semina Functional characterization of zebrafish orthologs of the human Beta 3-Glucosyltransferase B3GLCT gene mutated in Peters Plus Syndrome. PLoS ONE: 2017, 12(9);e0184903 PubMed 28926587
Harun Cakmak, Esra Gokmen, Gokay Bozkurt, Tolga Kocaturk, Kemal Ergin Effects of Sunitinib and Bevacizumab on VEGF and miRNA levels on corneal neovascularization. Cutan Ocul Toxicol: 2017;1-19 PubMed 28874077
Week 8 Stage 22
The images below link to virtual slides of the human developing eye at Carnegie stage 22. Click on the image to open or select specific regions from the regions of interest links.
Virtual Slide - Regions of Interest
Links: Embryo Virtual Slides
| The cornea ocular surface is composed of three epithelia, conjunctival, limbal and corneal.
Corneal epithelial cells cartoon
| The Adult Human Limbal Palisades of Vogt
Bar represents 500 μm in A and B, 200 μm in C and E, and 50 μm in D
Adult human limbal palisades of Vogt
Limbal Stem Cells
Cartoon showing the location of limbal stem cells at the limbal basal layer.
- Links: Stem Cells
Carnegie Stages - Eye
The following data is from a study of human embryonic carnegie stages and other sources.
- Stage 10 - optic primordia appear.
- Stage 11 - right and left optic primordia meet at the optic chiasma forming a U-shaped rim.
- Stage 12 - optic neural crest reaches its maximum extent and the optic vesicle becomes covered by a complete sheath,
- Stage 13 - By the end of the fourth week the optic vesicle lies close to the surface ectoderm. Optic evagination differentiation allows identification of optic part of retina, future pigmented layer of retina, and optic stalk. The surface ectoderm overlying the optic vesicle, in response to this contact, has thickened to form the lense placode.
- Stage 14 - (about 32 days) the lens placode is indented by the lens pit, cup-shaped and still communicates with the surface by a narrowing pore.
- Stage 15 - (about 33 days) the lens pit is closed. The lens vesicle and optic cup lie close to the surface ectoderm and appear to press against the surface.
- Stage 16 - (37 days) Growth of the lens body results in a D-shaped lens cavity. Perilental blood vessels (tunica vasculosa lentis) are visible. Prior to the development of the eyelids, one small sulcus or groove forms above the eye (eyelid groove) and another below it.
- Stages 17 - 19 - Retinal pigment is visible and the retinal fissure is largely closed. Eyelids grooves deepen, eyelid folds develop, first below, and then above, the eye.
- Stages 18 - Mesenchyme invades the region between the lens epithelium and the surface ectoderm.
- Stages 19 - 22 - the eyelid folds develop into the eyelids and cover more of the eye as the palpebral fissure takes shape. The upper and the lower eyelids meet at the outer canthus in Stage 19.
- Stage 20 - The lens cavity is lost and a lens suture begins to form. The inner canthus is established.
- Stage 23 - The retina comprises the pigmented layer, external limiting membrane, proliferative zone, external neuroblastic layer, transient fiber layer, internal neuroblastic layer, nerve fiber layer, and internal limiting membrane. Eyelids closure is complete (Note - shown as still open in the Kyoto embryo).
|Carnegie stage:||1 2 3 4||5 6||7 8 9||10 11 12 13||14 15||16 17||18 19||20 21 22 23|
Corneal endothelium basement membrane beginning in children at 3 μm thick and increases in adults to 10 μm. Consists of collagen type IV and VIII fibrils.
Composed of two layers:
- anterior banded layer - commencing in week 10 (GA week 12) as collagen lamellae and proteoglycans.
- posterior non-banded layer - deposited by endothelial cells over time and thickens postnatally over decades.
Descemet membrane was historically named after Jean Descemet (1732–1810) a French physician.
Neural crest-derived cells contribute to mouse cornea development.
This developmental timeline is from a recent frog (Xenopus laevis) cornea study
- stage 25 - cornea starts from a simple embryonic epidermis overlying the developing optic vesicle.
- stage 30 - detachment of the lens placode, cranial neural crest cells start to invade the space between the lens and the embryonic epidermis to construct the corneal endothelium.
- stage 41 - a second wave of migratory cells containing presumptive keratocytes invades the matrix leading to the formation of inner cornea and outer cornea. A unique cell mass (stroma attracting center) connects the two layers like the center pole of a tent.
- stage 48 - many secondary stromal keratocytes individually migrate to the center and form the stroma layer.
- stage 60 - the stroma space is filled by collagen lamellae and keratocytes, and the stroma attracting center disappears. At early metamorphosis, the embryonic epithelium gradually changes to the adult corneal epithelium, which is covered by microvilli.
- stage 62 - the embryonic epithelium thickens and cell death is observed in the epithelium, coinciding with eyelid opening.
- After metamorphosis - cornea has attained the adult structure of three cellular layers, epithelium, stroma, and endothelium, and between the cellular layers lie two acellular layers (Bowman's layer and Descemet's membrane)
- Links: Frog Development
Mouse Eye TGF-beta Model - Summary of the TGFβ-dependent development of anterior and posterior ocular structures. 
|a Neural crest-derived cells (NC, blue) contribute to structures of the anterior eye segment and the primary vitreous (PV).
||b In the cornea, prospective stromal keratocytes and endothelial cells are of neural crest origin.
- Peter Y Lwigale Corneal Development: Different Cells from a Common Progenitor. Prog Mol Biol Transl Sci: 2015, 134;43-59 PubMed 26310148
- Leona T Y Ho, Anthony M Harris, Hidetoshi Tanioka, Naoto Yagi, Shigeru Kinoshita, Bruce Caterson, Andrew J Quantock, Robert D Young, Keith M Meek A comparison of glycosaminoglycan distributions, keratan sulphate sulphation patterns and collagen fibril architecture from central to peripheral regions of the bovine cornea. Matrix Biol.: 2014, 38;59-68 PubMed 25019467
- Maki Kayama, Manae S Kurokawa, Hiroki Ueno, Noboru Suzuki Recent advances in corneal regeneration and possible application of embryonic stem cell-derived corneal epithelial cells. Clin Ophthalmol: 2007, 1(4);373-82 PubMed 19668514
- Wei Li, Yasutaka Hayashida, Ying-Ting Chen, Scheffer C G Tseng Niche regulation of corneal epithelial stem cells at the limbus. Cell Res.: 2007, 17(1);26-36 PubMed 17211449 | Cell Research
- A A Pearson The development of the eyelids. Part I. External features. J. Anat.: 1980, 130(Pt 1);33-42 PubMed 7364662
- Lars M Ittner, Heiko Wurdak, Kerstin Schwerdtfeger, Thomas Kunz, Fabian Ille, Per Leveen, Tord A Hjalt, Ueli Suter, Stefan Karlsson, Farhad Hafezi, Walter Born, Lukas Sommer Compound developmental eye disorders following inactivation of TGFbeta signaling in neural-crest stem cells. J. Biol.: 2005, 4(3);11 PubMed 16403239 | J Biol.
- Wanzhou Hu, Nasrin Haamedi, Jaehoon Lee, Tsutomu Kinoshita, Shin-ichi Ohnuma The structure and development of Xenopus laevis cornea. Exp. Eye Res.: 2013, 116;109-28 PubMed 23896054 | Exp Eye Res.
- Cornea "For corneal specialists and for all general ophthalmologists with an interest in this exciting subspecialty, Cornea brings together the latest clinical and basic research on the cornea and the anterior segment of the eye." [jour PuMed Listing]
Peter Y Lwigale Corneal Development: Different Cells from a Common Progenitor. Prog Mol Biol Transl Sci: 2015, 134;43-59 PubMed 26310148
Nick J R Maycock, John Marshall Genomics of corneal wound healing: a review of the literature. Acta Ophthalmol: 2014, 92(3);e170-84 PubMed 23819758
John R Hassell, David E Birk The molecular basis of corneal transparency. Exp. Eye Res.: 2010, 91(3);326-35 PubMed 20599432
The International Journal of Developmental Biology Vol. 48 Nos. 8/9 (2004) Eye Development
D M MAURICE The structure and transparency of the cornea. J. Physiol. (Lond.): 1957, 136(2);263-86 PubMed 13429485
Bookshelf cornea development
Search Pubmed: cornea development
Search Entrez: cornea development
- Limbal epithelial stem cells - cells located at the limbal basal layer.
- palisades of Vogt
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Cite this page: Hill, M.A. 2017 Embryology Vision - Cornea Development. Retrieved December 17, 2017, from https://embryology.med.unsw.edu.au/embryology/index.php/Vision_-_Cornea_Development
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