Corneal Epithelium

Corneal epithelium is a highly regenerative tissue engaged in continuous protein synthesis and requiring continuous transport of amino acids.

From: Ocular Transporters and Receptors , 2013

Diagnostic Evaluation

CHARLES V. TRIMARCHI , SUSAN A. NADIN-DAVIS , in Rabies (Second Edition), 2007

5.2.4 Corneal impressions

Corneal epithelium, while it can test positive for lyssavirus antigen in some patients with rabies, is difficult to sample correctly, especially from comatose patients. Because of the risk of permanent damage to the cornea, samples should be taken only by an ophthalmologist, after consultation with the rabies testing laboratory ( Zaidman and Billingsley, 1998). The sample is collected by vigorously rubbing a flat surface of a clean microscope slide on each cornea. Corneal impression slides are tested by immunofluorescence staining for viral antigen; they can also be tested by RT-PCR. The antigen appears characteristically as round to oval intracytoplasmic inclusions in corneal epithelial cells (see Figure 10.1D).

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Phototherapeutic keratectomy: operative techniques and complications

Timothy B. Cavanaugh , in Corneal Surgery (Fourth Edition), 2009

EPITHELIUM REMOVAL

Corneal epithelium removal is typically performed with a no. 64 or similar Beaver blade, but a blunt spatula, rotating brush, or alcohol may be used as well. In patients with recurrent erosion, all loose epithelia are first removed with a cellulose sponge. The Merocel sponge (Xomed Surgical Products, Inc., Jacksonville, FL) is preferred because it does not leave any fibers on the corneal surface. The epithelium may come off in incomplete sheets, so debridement should be complete, extending to the level of Bowman's layer. The no. 64 Beaver blade should be used (at an angle of 45° so that the blade scrapes but does not cut corneal tissue) to debride a wider margin, usually resulting in an approximately round corneal epithelial defect measuring about 7–9 mm. The Merocel sponge is then used to remove final epithelial remnants and dry the surface for visual inspection. In treatment of opacities, the edge of epithelial removal should never be in the visual axis to prevent a ridge in the line of vision; an additional margin of epithelium is often removed to prevent this.

In some cases, transepithelial ablation with the laser is preferable to mechanical removal. Subepithelial scar tissue should always be removed manually if possible, but in cases of significant surface irregularity caused by anterior stromal lesions, it may be best to ablate directly through corneal epithelium, taking advantage of the uncanny natural smoothing or masking ability of the laser. Determining an endpoint can be very challenging. Transepithelial ablation should be performed in a darkened room with a large-diameter ablation zone. Intact epithelium autofluoresces a light purple hue with laser beam interaction, but this hue changes to a dark purple/black when ablation begins to break through the epithelial layer. Ideally, the breakthrough spots should correspond to the elevated pathologic areas visualized before surgery at the slit lamp. Corneal epithelium and stroma ablate at slightly different rates, so one must be careful to pay special attention to the endpoint when epithelium and stroma are being ablated simultaneously.

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The Visual System

Jane Sowden , Andrea Streit , in Kaufman's Atlas of Mouse Development Supplement, 2016

Cornea

The corneal epithelium develops from the surface ectoderm overlying the lens vesicle. Secretion of extracellular matrix (ECM) molecules from this epithelium facilitates the inward migration of adjacent mesenchymal cells, which are predominantly of neural crest origin, with a small proportion of mesodermal cells ( Gage et al., 2005). These cells form the corneal endothelium and the keratocytes of the corneal stroma lying between the corneal endothelium and the outer corneal epithelium. By E14.5, the fluid-filled anterior chamber has formed as the differentiating corneal endothelium separates from the lens (illustrated in Kaufman's Atlas plate 53; Figure 20.1).

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Corneal Epithelium: Response to Infection

Elizabeth A. Szliter-Berger , L.D. Hazlett , in Encyclopedia of the Eye, 2010

The corneal epithelium must function as an effective barrier against the external environment and protect the eye from infectious agents, while concomitantly maintaining visual acuity. Epithelial defense mechanisms have evolved so as to allow efficient clearance of invading pathogens on the ocular surface without the need for continuous (and potentially damaging) inflammatory responses. As such, this article discusses how cells of the corneal epithelium are able to competently recognize pathogens and their by-products through toll-like receptor activation and signaling; the network of proinflammatory cytokines and chemokines produced and secreted that recruit inflammatory cells into the cornea; its expression of antimicrobial products; and its ability to promote wound healing and restoration of the cornea's visual integrity upon eradication of the pathogen.

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Organ Development

Joel B. Miesfeld , Nadean L. Brown , in Current Topics in Developmental Biology, 2019

2.1 Epithelium

The cornea epithelium originates from cells in the surface ectoderm, adjacent to both sides of the lens placode, termed presumptive corneal epithelium (pCE; Fig. 1). At this stage both the presumptive cornea and lens placode (pLP) express Pax6 (Fig. 1A and Table 1) (Collomb et al., 2013). Corneal epithelium formation immediately follows lens placode thickening, invagination, and separation from the overlying surface ectoderm (Fig. 1F). Once the lens placode has transited into a lens vesicle and detached from the surface ectoderm, the fusion of the adjacent Pax6 positive cells fuse to create a contiguous pCE (Fig. 1E). If proper levels of Pax6 are not present at this stage several corneal defects can occur, including cornea vascularization, epithelial thinning, and improper separation of the lens and cornea (Davis, Duncan, Robison, & Piatigorsky, 2003; Ramaesh et al., 2003). At this stage, corneal epithelial cells are multipotent, retaining an ability to develop as lens or epidermal cells, if the proper signals are not restricted. A possible mechanism for restricting lens fate is the presence of neural crest (known as periocular mesenchyme (POM)) and epiblast cells, which both express BMP inhibitors, a signal required for lens but not cornea formation (Collomb et al., 2013; Furuta & Hogan, 1998; Gerhart et al., 2009; Tzahor et al., 2003). To restrict epidermal fate the WNT inhibitor Dkk2 represses WNT signaling emanating from the forming corneal limbus (Mukhopadhyay et al., 2006). Another molecular switch that occurs during corneal development involves cytokeratin proteins. Epithelial precursors, in the surface ectoderm, generally express K5/K14, but the pCE switches to K8/K18, and then again, to cornea-specific keratins K3/K12, with K12 expression dependent on Pax6 (Chaloindufau, Sun, & Dhouailly, 1990; Liu, Kao, & Wilson, 1999; Shiraishi et al., 1998; Wolosin, Budak, & Akinci, 2004). Although the cornea starts out as 1–2 cell layers thick, containing flat, oval shaped cells, it grows to 6–8 cell layers, with the shape of each cell layer dependent on its final location. Pax6 expression is maintained throughout differentiation by the entire corneal epithelium, as well as by the stem cells of the corneal limbus, which replenish the epithelium as dead cells are removed throughout life (Hanna, Bicknell, & Obrien, 1961; Koroma, Tseng, & Sundin, 1997; Li et al., 2015).

Fig. 1

Fig. 1. Cornea and lens development. (A) The presumptive cornea epithelium (pCE) and lens placode (pLP) are located at the surface ectoderm (SE). At this stage induction of each cell type is inhibited by the presence of periocular mesenchymal cells (POM). (B) During optic vesicle (OV) morphogenesis, POM cells are relocated laterally, facilitating contact between the OV and LP, and initiation of lens induction. (C) Lens pit (LPi) invagination requires cell proliferation and apical constriction to form the spherical pit. As the pit is forming, the pCE cells are brought together. (D) The anterior side (A) of the lens vesicle (LV) fuses to form a stalk that is continuous with the pCE, but eventually pinches off to form an autonomous lens vesicle. The anterior-most cells of the lens vesicle coalesce into the epithelial cell layer, while primary fibergenesis begins on the posterior side (P) of the lens vesicle. (E) The pCE is now a contiguous cell layer at the surface, while underneath periocular mesenchyme cells once again populate the space between the pCE and lens vesicle. Meanwhile, differentiating primary lens fiber cells begin to extend toward the anterior. (F) The cornea epithelium (CEi), which starts out as 1–2 cell layers, but continues to thicken as development proceeds. The cornea stroma (CS) and endothelium (CEn) are derived from the periocular mesenchyme. (G) The mature lens is comprised of the anterior epithelial layer (AEL), equator (transition zone), secondary fiber and primary fiber cells. NR, neural retina; RPE, retina pigmented epithelium.

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Regeneration of Epidermal Structures

David L. Stocum , in Regenerative Biology and Medicine (Second Edition), 2012

C Regeneration of Corneal Epithelium

The corneal epithelium is the only part of the cornea that undergoes both maintenance and injury-induced regeneration. In many mammals the vertical turnover rate of the epithelium during maintenance regeneration is 7–14 days ( Haddad, 2000). Corneal epithelium will not regenerate properly after wounding in the absence of the limbus (Huang and Tseng, 1991). Long-term labeling studies with 3H-thymidine identified slow-cycling (label retaining) cells in the limbus that appeared to be the stem cells responsible for epithelial regeneration (Cotsarelis et al., 1989; Lavker et al., 1998; Pellegrini et al., 1999). These findings gave rise to a model of corneal regeneration in which limbal stem cells divide asymmetrically to produce transit amplifying cells that replace cells lost by turnover or injury as they migrate toward the center of the cornea (Buck, 1985; Auran et al., 1995; Tseng and Sun, 1999).

The results of transplantation experiments with genetically marked limbal and corneal epithelium have modified this model (Majo et al., 2008). Limbal fragments from a β-gal-ROSA26 mouse were grafted in place of similar sized limbal fragments of SCID mice, or a fragment of β-gal-ROSA26 central corneal epithelium was grafted in place of a SCID limbal fragment. The marked limbal cells did not contribute to the maintenance regeneration of the cornea, but the marked corneal epithelium did so (Fig. 3.9). The marked limbal and corneal grafts both contributed to the regeneration of the corneal epithelium after it was subjected to a large wound. Other experiments showed that central cornea transplants could adopt either a conjunctival or corneal phenotype depending on which niche environment they were located. These results suggest that both intact and wounded corneal epithelium is maintained by oligopotent stem cells within the corneal epithelium itself, and that limbal stem cells contribute mainly to injury-induced corneal regeneration. A survey of cultured cells from conjunctiva, limbus, peripheral cornea, intermediate cornea and central cornea in several mammalian species revealed clonogenic cells in each that expressed p63, a putative marker of corneal stem cells (Pelligrini et al., 2001), implying that, at least under injury conditions, the whole ocular surface is capable of contributing to corneal regeneration.

Figure 3.9. Experiments demonstrating that the limbus does not contribute to maintenance regeneration of the corneal epithelium, but does contribute to the epithelium during injury-induced regeneration, and that the corneal epithelium can also contribute to injury-induced regeneration. (A) Transplant of labeled (Lac Z) limbal cells (blue) to the edge of the cornea (green) in normal orientation. After three months of maintenance regeneration, no labeled cells have contributed to the corneal epithelium. (B) Transplant of labeled corneal epithelium (blue) in place of the limbus at the edge of the cornea. After four months, the corneal epithelium was removed (yellow). Seven days later, cells from the transplant have resurfaced the cornea (orange arrow) (C) Four months after transplanting labeled limbus to the edge of the cornea, the cornea was wounded (yellow). After 7 days, cell from the transplant have resurfaced the wound (orange arrow).

 After Majo et al., 2008.

Regulation of MMP-9 expression appears to be particularly important for the resurfacing of corneal wounds that penetrate the stroma, since MMP-9 is required to remove the fibrin matrix deposited in the wound bed (Mohan et al., 2002). MMP-9 is expressed by cells at the front of the migrating epithelium of corneal wounds (Matsubara et al., 1991a,b; Mohan et al., 2002). The expression of MMP-9 in healing corneal wounds must be precisely regulated for proper healing (Mohan et al., 2002). MMP-9 knockout mice heal corneal wounds faster, but the lack of MMP-9 also results in reduced ability to remove fibrin matrix, thus leading to opacity. Conversely, over expression of MMP-9 is associated with cutaneous and ocular surface diseases such as epidermolysis bullosa, cicatrial pemphigoid and corneal epithelial erosions. Two growth factor families, TGF-β and Il-1, mediate the induction of MMP-9 during epithelial resurfacing (Gordon et al., 2009).

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Anatomy of the eye and orbit

John V. Forrester MB ChB MD FRCS(Ed) FRCP(Glasg) (Hon) FRCOphth(Hon) FMedSci FRSE FARVO , ... Eric Pearlman BSc PhD , in The Eye (Fourth Edition), 2016

Corneal epithelium (Fig. 1-12B).

The corneal epithelium is a stratified (possessing five or six layers) squamous non-keratinized epithelium (the superficial cells are flattened, nucleated and non-keratinized). It is 50–60 µm in thickness and adjacent cells are held together by numerous desmosomes and to the underlying basal lamina by hemidesmosomes and anchoring filaments (Fig. 1-12B). The anterior surface of the corneal epithelium is characterized by numerous microvilli and microplicae (ridges) whose glycocalyx coat interacts with, and helps stabilize, the precorneal tear film. New cells are derived from mitotic activity in the limbal basal cell layer (see p. 211) and these displace existing cells both superficially and centripetally. The corneal epithelium responds rapidly to repair disruptions in its integrity by amoeboid sliding movements of cells on the wound margin followed by cell replication.

The basal epithelial cells rest on a thin, but prominent, basal lamina (lamina lucida, 25 nm; lamina densa, 50 nm). Corneal epithelial adhesion is maintained by a basement membrane complex, which anchors the epithelium to Bowman's layer via a complex mesh of anchoring fibrils (type VII collagen) and anchoring plaques (type VI collagen), which interact with the lamina densa and the collagen fibrils of Bowman's layer. The corneal epithelium is devoid of melanocytes. Myeloid-derived major histocompatibility complex (MHC) class II antigen-positive dendritic cells (Langerhans cells) are present in the limbus and peripheral cornea (Fig. 1-12), but decline sharply in density in a centripetal gradient, and are rare in the central cornea. However, MHC class II-negative dendritic cells have been identified in the mouse central cornea and recent in vivo confocal microscopy (IVCM) (Fig. 1-13) suggests that the normal human central corneal epithelium contains dendritic cells although their immunophenotype cannot be ascertained from IVCM. The comparative paucity of potential antigen-presenting cells, such as dendritic cells, and the avascular nature of the cornea are considered factors crucial to the success of corneal grafting (see Ch. 7).

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Cornea Overview

P. Asbell , D. Brocks , in Encyclopedia of the Eye, 2010

Epithelium

The corneal epithelium is composed of approximately 5–6 rows of stratified squamous epithelial cells. It is these cells in this configuration, along with the overlying tear film that help create the smooth, clear surface. The tight junctions between epithelial cells help to prevent the penetration of microbes and fluid into the corneal stroma.

Epithelial cells are continuously being created by the basal limbal stem cells. New cells slowly migrate to the corneal surface where devitalized cells are lost and washed away in the tear film. The entire process takes approximately 2   weeks.

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Molecular Biology of Eye Disease

Allen O. Eghrari , ... John D. Gottsch , in Progress in Molecular Biology and Translational Science, 2015

1.1 Epithelium

The corneal epithelium is composed of four to six layers of nonkeratinized, stratified squamous epithelial cells, and in humans, it measures approximately 50  μm in thickness.

The most superficial two to three layers are flat and polygonal in shape 1 with apical microvilli and microplicae, and covered by a charged glycocalyx, 2 which maximizes surface area with the mucinous layer of the tear film. At the cell periphery, tight junctions provide a watertight seal and assist in the prevention of pathogenic organisms from entering the cornea.

Directly posterior, the wing or suprabasal cells contribute a two- to three-cell thick layer and also demonstrate tight junction complexes between cells.

Basal epithelial cells represent the posterior-most layer of the corneal epithelium. Perilimbal basal epithelial cells differentiate and migrate anteriorly to repopulate the cornea; microvilli appear on the surface gradually during this process of maturation. Basal epithelial cells utilize hemidesmosomes to adhere to the underlying basement membrane and underlying stroma. The hemidesmosome, anchoring fibril, and anchoring filament complex produce an anchoring complex, which represents a common link between the intracellular cytoskeleton of the basal epithelial cell and the stroma posteriorly. 3

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Pathology

John V. Forrester MB ChB MD FRCS(Ed) FRCP(Glasg) (Hon) FRCOphth(Hon) FMedSci FRSE FARVO , ... Eric Pearlman BSc PhD , in The Eye (Fourth Edition), 2016

Healing in the cornea usually leads to a corneal opacity (scar)

The corneal epithelium regenerates at the limbus (limbal stem cells, see Ch. 4, p. 211) and spreads rapidly across the cornea. Bowman's layer does not regenerate. Stromal keratocytes transform into fibro­blasts to heal stromal wounds. Transparency is lost because the collagen fibres are not aligned properly (see Ch. 4, p. 203). Desçemet's membrane does not regenerate. The corneal endothelium fills in defects by sliding and in so doing deposits secondary layers in Desçemet's membrane: the membrane is elastic and there is often recoil at the edge of a deficit.

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