MECHANISMS OF CORNEAL EPITHELIAL WOUND-HEALING

A mathematical model has been developed to describe the overall cornea l epithelial wound healing process. Following surgery or trauma to the corneal epithelium, the repair of damage to the cell layers is essent ial for the maintenance of normal visual acuity. Evidence suggests tha t epithelial wound healing consists of a healing phase during which ce ll migration occurs to effect wound closure and cell mitosis restores the epithelial cell density to unwounded levels. Epidermal growth fact or (EGF) has been shown to increase the rate of corneal wound healing for a variety of wound types. However, due to the complexities of woun d healing, and different effects of EGF on the various processes that constitute wound healing, an optimal EGF therapeutic regimen is unknow n and difficult to determine experimentally. The model accounts for EG F-mediated cell migration and cell mitosis. All necessary model parame ters, including cell migration coefficient, cell cycle times and tear concentrations of EGF after wounding, were determined independently us ing in vitro and in vivo techniques. The effect of EGF from endogenous and exogenous sources on wound closure kinetics was predicted by dete rmining the intercellular EGF concentrations based on tear how dynamic arguments. Model simulation results are in agreement with in vivo wou nd healing data. Clinically convenient optimal EGF therapeutic regimen s were determined using model simulations. Copyright (C) 1996 Elsevier Science Ltd