Corneal surface regeneration: epithelial sheets to epithelial crypts

The corneal surface is the most important 123 square millimetres of the body’s surface. Its health is paramount for sight. Due to its exposed nature it is vulnerable to environmental insults causing minor to excessive epithelial cell loss. Large epithelial defects, with an intact limbus heal by the formation of 3 to 6 convex sheets that migrate centripetally, meet adjacent sheets and undergo contact inhibition to form geometric shapes. These finally close by the formation of ‘Y’ shaped contact lines (Rule 1). When the limbus is partially involved, there is a preferential healing of the limbus by circumferential migration of tongue shaped sheets from the remaining intact limbus. These meet to cover the limbus (Rule 2) and subsequent healing occurs as in rule 1. On occasions conjunctival epithelium migrates across the limbus resulting in partial limbal deficiency. When the entire limbus is affected, total conjunctivalisation of the cornea occurs (Rule 3). Within sheets, individual cells migrate in a predominantly clockwise whorl pattern (Rule 4). Physiological and wound healing related cell turnover is believed to occur from stem cells (SC) located at the limbus. Specialised anatomical structures, termed Limbal Epithelial Crypts (LEC) are associated with some limbal palisades and present all the hallmarks of a SC niche. SC characteristics are also seen in the peripheral cornea adjacent to a palisade with a LEC. Recent evidence suggests that the limbal SC play a critical role in wound healing but may have only a marginal role physiological corneal epithelial homeostasis.