Epithelium
The epithelium constitutes 5%–10% of the total corneal thickness. Surface projections (microvilli and microplicae) are present on the apical surface of the most superficial cell layer of epithelium. These projections are coated with filamentous material known as glycocalyx. Mucin glycoproteins, the major constituents of glycocalyx, are thought to promote both stability of the tear film and wettability of the corneal surface (Fig 8-1).
Plasma membrane proteins and the lipids of corneal epithelial cells, similar to those of other cell types, are heavily glycosylated and play an important role in cell–cell adhesion as well as in adhesion of the basal cells of the corneal epithelium to the underlying basement membrane. The sugar residues of the plasma membrane glycoproteins and the glycolipids of corneal epithelium also play a role in wound-healing mechanisms; they do so by mediating corneal epithelial sheet migration over the wound surface following ocular injury. These residues also contribute to the pathogenesis of corneal infection by serving as attachment sites for microbes. The normal rate of epithelial cell migration is 2 mm per day and is adversely affected by preservatives in topical eyedrops.
Beginning with the discovery of the centripetal cell migration that occurs in the cornea, early studies on epithelial cell renewal led to the conclusion that the proliferative source of the corneal epithelium resides at the limbus. Interestingly, results of a more recent study suggest that corneal stem cells may also exist in the central cornea. The limbus is characterized by stromal invaginations known in humans as the palisades of Vogt (see Chapter 2, Fig 2-8A). These papillae-like projections show a distinctive vasculature with radially oriented arterial and venous components. The palisades of Vogt have been suggested as the reservoir that
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protects stem cells from traumatic and environmental insults
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allows epithelial–mesenchymal interactions
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provides access to chemical signals that diffuse from the rich underlying vascular network
Normal corneal epithelium remains in a steady state in which cell proliferation is necessary to replace cells lost by terminal differentiation and desquamation (Fig 8-2). While basal cells of the central cornea proliferate actively, basal cells at the limbus consist of a mixture of slow-cycling stem cells and their progeny, transient amplifying (TA) cells, which are affected by growth factors, cytokines, and extracellular matrix. During treatment of corneal wounds with cryopreserved amniotic membrane, TA cells are likely upregulated to enhance wound healing.
Penetration of the Corneal Epithelium
Hydrophilic molecules penetrate the epithelium poorly, but they may pass through tight junctions if the polar molecule has a mass lower than 500 Da. Hydrophilic drugs can also reach very high corneal penetration levels when the corneal epithelium is damaged or inflamed. The dissociation constant (also called ionization constant) is likewise important in determining a molecule’s permeability across the cornea. To diffuse across the epithelium, organic molecules should be in an uncharged state. However, a charged molecule can more readily penetrate the stroma. To penetrate the cornea and enter the anterior chamber, therefore, an organic molecule should be able to dissociate at physiologic pH and temperature (ie, within the stroma).
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Majo F, Rochat A, Nicolas M, Jaoudé GA, Barrandon Y. Oligopotent stem cells are distributed throughout the mammalian ocular surface. Nature. 2008;456(7219):250–254.
Excerpted from BCSC 2020-2021 series: Section 2 - Fundamentals and Principles of Ophthalmology. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.