Vision - Cornea Development
|Embryology - 29 Jun 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).
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.
Rozemarijn S Verhoeven, Andres Garcia, RiLee Robeson, Brian C Gilger, David Culp, Craig Struble, Lee Hamm, Tomas Navratil, Benjamin Yerxa Nonclinical Development of ENV905 (Difluprednate) Ophthalmic Implant for the Treatment of Inflammation and Pain Associated with Ocular Surgery. J Ocul Pharmacol Ther: 2017; PubMed 28650720
Rajesh Subhash Joshi Postoperative posterior capsular striae and the posterior capsular opacification in patients implanted with two types of intraocular lens material. Indian J Ophthalmol: 2017, 65(6);466-471 PubMed 28643710
Agustin Melo-Carrillo, Rodrigo Noseda, Rony Nir, Aaron Schain, Jennifer Stratton, Andrew M Strassman, Rami Burstein Selective inhibition of trigeminovascular neurons by fremanezumab - a humanized monoclonal anti-CGRP antibody. J. Neurosci.: 2017; PubMed 28642283
Hosoon Choi, Casie Phillips, Joo Youn Oh, Eileen M Stock, Dong-Ki Kim, Jae-Kyung Won, Samuel Fulcher Comprehensive Modeling of Corneal Alkali Injury in the Rat Eye. Curr. Eye Res.: 2017;1-10 PubMed 28636415
Marie H Solheim, Allen C Clermont, Jonathon N Winnay, Erlend Hallstensen, Anders Molven, Pål R Njølstad, Eyvind Rødahl, C Ronald Kahn Iris Malformation and Anterior Segment Dysgenesis in Mice and Humans With a Mutation in PI 3-Kinase. Invest. Ophthalmol. Vis. Sci.: 2017, 58(7);3100-3106 PubMed 28632845
James K Kubilus, Carolina Zapater I Morales, Thomas F Linsenmayer The Corneal Epithelial Barrier and Its Developmental Role in Isolating Corneal Epithelial and Conjunctival Cells From One Another. Invest. Ophthalmol. Vis. Sci.: 2017, 58(3);1665-1672 PubMed 28319640
Seungwoon Seo, Lisheng Chen, Wenzhong Liu, Demin Zhao, Kathryn M Schultz, Amy Sasman, Ting Liu, Hao F Zhang, Philip J Gage, Tsutomu Kume Foxc1 and Foxc2 in the Neural Crest Are Required for Ocular Anterior Segment Development. Invest. Ophthalmol. Vis. Sci.: 2017, 58(3);1368-1377 PubMed 28253399
Geng Wang, Na Li, Xiaohong Lv, Naila Ahmed, Xinlei Li, Huidong Liu, Jing Ma, Yafang Zhang Triptolide suppresses alkali burn-induced corneal angiogenesis along with a downregulation of VEGFA and VEGFC expression. Anat Rec (Hoboken): 2017; PubMed 28233432
Ana F Ojeda, Ravi P Munjaal, Peter Y Lwigale Knockdown of CXCL14 disrupts neurovascular patterning during ocular development. Dev. Biol.: 2017; PubMed 28095300
Gisela Kalkum, Susanne Pitz, Nesrin Karabul, Michael Beck, Guillem Pintos-Morell, Rossella Parini, Marianne Rohrbach, Svetlana Bizjajeva, Uma Ramaswami Paediatric Fabry disease: prognostic significance of ocular changes for disease severity. BMC Ophthalmol: 2016, 16(1);202 PubMed 27852300
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.
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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- UNSW SoMS research - Ocular Diseases Research Group
- UNSW Virtual Slides Eye Development Histology (requires login)
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Cite this page: Hill, M.A. 2017 Embryology Vision - Cornea Development. Retrieved June 29, 2017, from https://embryology.med.unsw.edu.au/embryology/index.php/Vision_-_Cornea_Development
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