Everett Kinsey Lecture. Keratocyte apoptosis in refractive surgery.

PURPOSE: The purpose of this paper is to review the relevance of keratocyte programmed cell death (apoptosis) in response to epithelial injury to corneal wound healing following refractive surgery and the pathogenesis of corneal diseases such as keratoconus.

METHODS

The TUNEL assay (to detect DNA fragmentation in situ) DNA laddering assay, and transmission electron microscopy have been used to detect apoptosis in human and animal corneas and cultured corneal cells. Molecular and cell biologic techniques have been used to study the cytokine-receptor systems that are involved in modulating apoptosis in the cornea.

RESULTS

Keratocyte apoptosis, mediated through the release of cytokines such as soluble Fas ligand and interleukin-1 from the injured epithelium, occurs following refractive surgical procedures like photorefractive keratectomy (PRK) and laser in situ keratomileusis (LASIK). Keratocytes that die in the anterior stroma following PRK or along the lamellar cut following LASIK are replenished in 2 to 4 days by proliferation and migration. The replenishing cells are activated myofibroblastic keratocytes that produce collagen, hyaluronic acid, growth factors modulating epithelial healing, and other components of the wound healing response. Keratocyte apoptosis can be inhibited by transepithelial PRK (probably by photodisruption of the apoptotic cytokines in the epithelium) or pharmacologic agents.

CONCLUSIONS

Keratocyte apoptosis may be an initiator of the wound healing response in the cornea. Control of this response has the potential to regulate wound healing in the cornea in response to PRK or LASIK. Recent evidence suggests that keratocyte apoptosis mediated by chronic epithelial injury could have a role in the pathogenesis of keratoconus.