Molecular Cell Biology for the Refractive Corneal Surgeon: Programmed Cell Death and Wound Healing

BACKGROUND: Variability of outcome following refractive surgical procedures is affected by corneal wound healing. Interactions between the corneal epithelium and stromal keratocytes affect both stromal remodeling and healing of the epithelium. These processes contribute to regression of initial effect, surface irregularity, and stromal scarring that occur following excimer laser photorefractive keratectomy (PRK). I review recent discoveries related to stromal-epithelial molecular interactions that provide insights into the cellular responses to refractive surgical procedures. RESULTS: Injury to the corneal epithelium stimulates programmed cell death (apoptosis) of the underlying anterior stromal keratocytes. I hypothesize that apoptosis of the keratocytes occurring immediately after epithelial injury associated with refractive surgical procedures initiates the subsequent wound healing response. Activated keratocytes subsequently repopulate the anterior corneal stroma where they produce collagen and other components associated with stromal remodeling. In addition, secretion of hepatocyte growth factor and keratinocyte growth factor by keratocytes increases after corneal epithelial wounding and these growth factors stimulate proliferation and inhibit differentiation of epithelial cells, effects which could promote epithelial hyperplasia associated with regression after photorefractive keratectomy. CONCLUSION: Corneal stromal-epithelial interactions help explain the different results that occur following excimer laser photorefractive keratectomy and laser in situ keratomileusis.