Vision - Cornea Development

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Introduction

Cornea structure
Human embryonic cornea
Human embryonic cornea (Week 8, Carnegie stage 22)
Human embryonic cornea
Human embryonic cornea detail (Week 8, Carnegie stage 22)
Section through front of Eyeball
Section through human cornea

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.


Vision Links: Introduction | Lens | Retina | Placodes | Extraocular Muscle | Cornea | Eyelid | Abnormalities | Student project 1 | Student project 2 | Category:Vision
Historic Embryology  
1906 Eye Embryology | 1907 Development Atlas | 1912 Eye Development | 1912 Nasolacrimal Duct | 1918 Grays Anatomy | 1921 Eye Development | 1922 Optic Primordia | 1925 Iris | 1927 Oculomotor | 1928 Human Retina | 1928 Retina | 1928 Hyaloid Canal | Historic Disclaimer
Links: Category:Cornea | Neural Crest Development | Integumentary Development

Some Recent Findings

  • Review - Corneal Development Different Cells from a Common Progenitor[1] "Development of the vertebrate cornea is a multistep process that involves cellular interactions between various ectodermal-derived tissues. Bilateral interactions between the neural ectoderm-derived optic vesicles and the cranial ectoderm give rise to the presumptive corneal epithelium and other epithelia of the ocular surface. Interactions between the neural tube and the adjacent ectoderm give rise to the neural crest cells, a highly migratory and multipotent cell population. Neural crest cells migrate between the lens and presumptive corneal epithelium to form the corneal endothelium and the stromal keratocytes. The sensory nerves that abundantly innervate the corneal stroma and epithelium originate from the neural crest- and ectodermal placode-derived trigeminal ganglion."
  • Bovine cornea extracellular matrix structure[2] "Electron microscopy and X-ray fibre diffraction were used to ascertain collagen fibril architecture. The bovine cornea was 1021±5.42μm thick at its outer periphery, defined as 9-12mm from the corneal centre, compared to 844±8.10μm at the centre. The outer periphery of the cornea was marginally, but not significantly, more hydrated than the centre (H=4.3 vs. H=3.7), and was more abundant in hydroxyproline (0.12 vs. 0.06mg/mg dry weight of cornea). DMMB assays indicated no change in the total amount of sulphated GAG across the cornea. Immunohistochemistry revealed the presence of both high- and low-sulphated epitopes of KS, as well as DS, throughout the cornea, and CS only in the peripheral cornea before the limbus. Quantification by ELISA, disclosed that although both high- and low-sulphated KS remained constant throughout stromal depth at different radial positions, high-sulphated epitopes remained constant from the corneal centre to outer-periphery, whereas low-sulphated epitopes increased significantly.
More recent papers
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This table shows an automated computer PubMed search using the listed sub-heading term.

  • Therefore the list of references do not reflect any editorial selection of material based on content or relevance.
  • References appear in this list based upon the date of the actual page viewing.

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.

Links: References | Discussion Page | Pubmed Most Recent | Journal Searches


Search term: Cornea Development

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


Search term: Cornea Embryology

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

Human Cornea

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.

Stage 22 - Eye and Nose

Stage 22 image 008.jpg

 ‎‎Mobile | Desktop | Original

Stage 22 | Embryo Slides
Stage 22 - Eye

Stage 22 image 008-eye.jpg

 ‎‎Mobile | Desktop | Original

Stage 22 | Embryo Slides

Virtual Slide - Regions of Interest

Links: Embryo Virtual Slides

Cornea Epithelia

The cornea ocular surface is composed of three epithelia, conjunctival, limbal and corneal.
  • Limbal stem cells are located in the palisades of Vogt, the transitional zone between the cornea and the conjunctiva.
  • Limbal stem cells are close to blood vessels.
  • They generate transient amplifying cells that terminally differentiate after a discrete number of cell divisions to corneal epithelial cells and undergo both centripetal migration and vertical migration.
Corneal Epithelial Cells cartoon

Corneal epithelial cells cartoon[3]

The Adult Human Limbal Palisades of Vogt
  • A - Palisades of Vogt (arrow) are readily recognized in the human limbus.
  • B - Such a unique pigmented structure can be identified on the flat mount preparation of Dispase-isolated human limbal epithelial sheets.
  • C - In donors with a darker skin, these palisades of Vogt are pigmented (arrow).
  • D - Under higher magnification, these limbal areas show undulated epithelial papillae (stars).
  • E - Hematoxyline staining highlights higher stratification and more undulation of the limbal epithelium, and the underlying limbal stroma has high cellularity and vascularity (arrow shows blood vessel).

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

Adult human limbal palisades of Vogt[4]

Limbal Stem Cells

Limbal stem cell niche cartoon PMID17211449.jpg

Cartoon showing the location of limbal stem cells at the limbal basal layer.[4]


Links: Stem Cells

Carnegie Stages - Eye

The following data is from a study of human embryonic carnegie stages[5] 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).
Week: 1 2 3 4 5 6 7 8
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

Descemet Membrane

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:

  1. anterior banded layer - commencing in week 10 (GA week 12) as collagen lamellae and proteoglycans.
  2. 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.

Mouse Cornea

histology Mouse eye neural crest

Neural crest-derived cells contribute to mouse cornea development.[6]

  • a Toluidine blue staining of an adult eye. The boxed areas correspond to b and c
  • b A detailed view of the corneal assembly, including outer epithelium, stroma, and inner endothelium
  • c The chamber angle at the irido-corneal transition which includes the trabecular meshwork (tm).
  • d-j In vivo fate mapping of NC-derived, β-galactosidase (βGal)-expressing cells (blue)
  • d The NC origin of corneal keratocytes (arrows) and of corneal endothelium (arrowhead).
  • e Structures of the chamber angle, including the trabecular meshwork are seen to be NC-derived.
  • f At E10, the optic cup is surrounded by NC-derived cells expressing βGal.
  • g-i The majority of the cells in the periocular mesenchyme (arrows), which forms the anterior eye segment, are of NC origin, as assessed from E11.5 to E13.5.
  • j The primary vitreous at E13.5 (arrowheads) shows a strong NC contribution.

Frog Cornea

This developmental timeline is from a recent frog (Xenopus laevis) cornea study[7]

  • 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)

Xenopus cornea development timeline


Links: Frog Development

Molecular

Mouse eye TGF-beta model.jpg

Mouse Eye TGF-beta Model - Summary of the TGFβ-dependent development of anterior and posterior ocular structures. [6]

a Neural crest-derived cells (NC, blue) contribute to structures of the anterior eye segment and the primary vitreous (PV).
  • TGFβ signaling is involved in the formation of the ciliary body (CB) and the trabecular meshwork (TM), and in control of PV growth.
  • Moreover, normal PV development and/or TGFβ signaling are important for correct retinal patterning.
b In the cornea, prospective stromal keratocytes and endothelial cells are of neural crest origin.
  • Here, TGFβ signaling is needed for the expression of the transcription factors Foxc1 and Pitx2 and for normal differentiation of NC-derived cells into collagen-synthesizing stromal keratocytes.
  • Moreover, in forming corneal endothelial cells (and in the TM), expression of Foxc1 and cell survival requires TGFβ signalling.

Additional Images

Historic Images

References

  1. Peter Y Lwigale Corneal Development: Different Cells from a Common Progenitor. Prog Mol Biol Transl Sci: 2015, 134;43-59 PubMed 26310148
  2. 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
  3. 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
  4. 4.0 4.1 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
  5. A A Pearson The development of the eyelids. Part I. External features. J. Anat.: 1980, 130(Pt 1);33-42 PubMed 7364662
  6. 6.0 6.1 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.
  7. 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.

Journals

  • 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]

Reviews

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

| PMC3726544 Barry R Masters Correlation of histology and linear and nonlinear microscopy of the living human cornea. J Biophotonics: 2009, 2(3);127-39 PubMed 19343693


The International Journal of Developmental Biology Vol. 48 Nos. 8/9 (2004) Eye Development

Articles

D M MAURICE The structure and transparency of the cornea. J. Physiol. (Lond.): 1957, 136(2);263-86 PubMed 13429485

| PMC1358888


Bookshelf cornea development

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Terms

  • 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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