Talk:Vision - Cornea Development

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Cite this page: Hill, M.A. (2024, April 17) Embryology Vision - Cornea Development. Retrieved from


Overview of the Cornea: Structure, Function, and Development

Prog Mol Biol Transl Sci. 2015;134:7-23. doi: 10.1016/bs.pmbts.2015.04.001. Epub 2015 Jun 4.

Eghrari AO1, Riazuddin SA1, Gottsch JD2.


The cornea is a transparent tissue with significant refractive and barrier functions. The epithelium serves as the principal barrier to fluid and pathogens, a function performed through production of tight junctions, and constant repopulation through differentiation and maturation of dividing cells in its basal cell layer. It is supported posteriorly by basement membrane and Bowman's layer and assists in maintenance of stromal dehydration. The stroma composes the majority of corneal volume, provides support and clarity, and assists in ocular immunity. The posterior cornea, composed of Descemet membrane and endothelium, is essential for stromal dehydration, maintained through tight junctions and endothelial pumps. Corneal development begins with primitive formation of epithelium and lens, followed by waves of migration from cells of neural crest origin between these two structures to produce the stroma and endothelium. Descemet membrane is secreted by the latter and gradually thickens. © 2015 Elsevier Inc. All rights reserved. KEYWORDS: Cornea; Corneal development; Corneal structure; Descemet membrane; Endothelium; Epithelium; Stroma PMID: 26310146

Corneal Development: Different Cells from a Common Progenitor

Prog Mol Biol Transl Sci. 2015;134:43-59. doi: 10.1016/bs.pmbts.2015.04.003. Epub 2015 Jun 4.

Lwigale PY.


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. Concomitant with corneal innervation is the formation of the limbal vascular plexus and the establishment of corneal avascularity. This review summarizes historical and current research to provide an overview of the genesis of the cellular layers of the cornea, corneal innervation, and avascularity. © 2015 Elsevier Inc. All rights reserved. KEYWORDS: Corneal avascularity; Corneal development; Corneal innervation; Neural crest cells

PMID 26310148


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 Jul 11. pii: S0945-053X(14)00097-3. doi: 10.1016/j.matbio.2014.06.004. [Epub ahead of print]

Ho LT1, Harris AM2, Tanioka H3, Yagi N4, Kinoshita S3, Caterson B2, Quantock AJ1, Young RD1, Meek KM5.


This study investigated changes in collagen fibril architecture and the sulphation status of keratan sulphate (KS) glycosaminoglycan (GAG) epitopes from central to peripheral corneal regions. Freshly excised adult bovine corneal tissue was examined as a function of radial position from the centre of the cornea outwards. Corneal thickness, tissue hydration, hydroxyproline content, and the total amount of sulphated GAG were all measured. High and low-sulphated epitopes of keratan sulphate were studied by immunohistochemistry and quantified by ELISA. Chondroitin sulphate (CS) and dermatan sulphate (DS) distributions were observed by immunohistochemistry following specific enzyme digestions. 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. Both small angle X-ray diffraction and TEM analysis revealed that collagen fibril diameter remained relatively constant until the outer periphery was reached, after which fibrils became more widely spaced (from small angle x-ray diffraction analysis) and of larger diameter as they approached the sclera. Depth-profiled synchrotron microbeam analyses showed that, at different radial positions from the corneal centre outwards, fibril diameter was greater superficially than in deeper stromal regions. The interfibrillar spacing was also higher at mid-depth in the stroma than it was in anterior and posterior stromal regions. Collagen fibrils in the bovine cornea exhibited a fairly consistent spacing and diameter from the corneal centre to the 12mm radial position, after which a significant increase was seen. While the constancy of the overall sulphation levels of proteoglycans in the cornea may correlate with the fibrillar architecture, there was no correlation between the latter and the distribution of low-sulphated KS. Copyright © 2014. Published by Elsevier B.V. KEYWORDS: Collagen structure; Cornea; Glycosaminoglycans; Proteoglycans

PMID 25019467



The molecular basis of corneal transparency

Exp Eye Res. 2010 Sep;91(3):326-35. doi: 10.1016/j.exer.2010.06.021. Epub 2010 Jul 3.

Hassell JR1, Birk DE.


The cornea consists primarily of three layers: an outer layer containing an epithelium, a middle stromal layer consisting of a collagen-rich extracellular matrix (ECM) interspersed with keratocytes and an inner layer of endothelial cells. The stroma consists of dense, regularly packed collagen fibrils arranged as orthogonal layers or lamellae. The corneal stroma is unique in having a homogeneous distribution of small diameter 25-30 nm fibrils that are regularly packed within lamellae and this arrangement minimizes light scattering permitting transparency. The ECM of the corneal stroma consists primarily of collagen type I with lesser amounts of collagen type V and four proteoglycans: three with keratan sulfate chains; lumican, keratocan, osteoglycin and one with a chondroitin sulfate chain; decorin. It is the core proteins of these proteoglycans and collagen type V that regulate the growth of collagen fibrils. The overall size of the proteoglycans are small enough to fit in the spaces between the collagen fibrils and regulate their spacing. The stroma is formed during development by neural crest cells that migrate into the space between the corneal epithelium and corneal endothelium and become keratoblasts. The keratoblasts proliferate and synthesize high levels of hyaluronan to form an embryonic corneal stroma ECM. The keratoblasts differentiate into keratocytes which synthesize high levels of collagens and keratan sulfate proteoglycans that replace the hyaluronan/water-rich ECM with the densely packed collagen fibril-type ECM seen in transparent adult corneas. When an incisional wound through the epithelium into stroma occurs the keratocytes become hypercellular myofibroblasts. These can later become wound fibroblasts, which provides continued transparency or become myofibroblasts that produce a disorganized ECM resulting in corneal opacity. The growth factors IGF-I/II are likely responsible for the formation of the well organized ECM associated with transparency produced by keratocytes during development and by the wound fibroblast during repair. In contrast, TGF-beta would cause the formation of the myofibroblast that produces corneal scaring. Thus, the growth factor mediated synthesis of several different collagen types and the core proteins of several different leucine-rich type proteoglycans as well as posttranslational modifications of the collagens and the proteoglycans are required to produce collagen fibrils with the size and spacing needed for corneal stromal transparency. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

PMID 20599432