Corneal Epithelium

The corneal epithelium is the outermost layer of the cornea. It is composed of a single layer of basal cells and 4-5 cell layers of nonkeratinized, stratified squamous epithelial cells, which are held together by tight junctions, to form an effective barrier against fluid loss and pathogen penetration.

The corneal epithelium develops from the head surface ectoderm overlying the developing lens. The bi-layered primitive epithelium is first apparent at about week five of human gestation. Later, the lens completes its formation, detaches from the corneal epithelium and eyelids form and fuse, overlying the corneal epithelium. At this stage, a wave of neural crest cells migrates into the space between the corneal epithelium and the lens. These cells form the corneal endothelium and the stromal keratocytes. Upon opening of the eyelids (week 24 of gestation in humans, 12 days after birth in mice), the primitive epithelium starts to stratify and form the mature corneal epithelium, with about six-seven cell layers. Along with changes in the number of cell layers, the basal epithelial cells change their shape from a flattened, ovoid appearance to cuboidal cells, which later become columnar. As cells leave the basal layer, they begin to flatten and form the superbasal wing-like cells. The cells continue to stratify upwards, and continue to flatten and form the superficial cell layers, which contain tight junctions. Unlike the epidermis, corneal epithelium cells do not lose their nucleus or undergo extensive keratinization.

Maintenance of the adult corneal epithelium is a dynamic process incorporating constant cell production, movement and loss and is essential for normal vision. According to the conventional hypothesis, slowly dividing limbal epithelial stem cells (LESCs), located in the basal limbal epithelium maintain the corneal epithelium. The LESCs produce transient amplifying cells (TACs) that centripetally migrate from the limbal region to the cornea, through the basal/superbasal layers to the outer stratified layers and are finally shed from the tissue surface. The limbal epithelium contains early TACs as well as LESCs. Although a number of markers are enriched in the basal limbal epithelium, no single marker has been unambiguously confirmed as LESC-specific. Recently, an alternative view proposes that corneal epithelial stem cells (CESCs), scattered throughout the basal layer of the corneal epithelium, are responsible for homeostatic maintenance of the tissue and that LESCs are only active during wound healing.