Mechanisms of corneal epithelial wound healing

A mathematical model has been developed to describe the overall corneal epithelial wound healing process. Following surgery or trauma to the corneal epithelium, the repair of damage to the cell layers is essential for the maintenance of normal visual acuity. Evidence suggests that epithelial wound healing consists of a healing phase during which cell migration occurs to effect wound closure and cell mitosis restores the epithelial cell density to unwounded levels. Epidermal growth factor (EGF) has been shown to increase the rate of corneal wound healing for a variety of wound types. However, due to the complexities of wound healing, and different effects of EGF on the various processes that constitute wound healing, an optimal EGF therapeutic regimen is unknown and difficult to determine experimentally. The model accounts for EGF-mediated cell migration and cell mitosis. All necessary model parameters, including cell migration coefficient, cell cycle times and tear concentrations of EGF after wounding, were determined independently using in vitro and in vivo techniques. The effect of EGF from endogenous and exogenous sources on wound closure kinetics was predicted by determining the intercellular EGF concentrations based on tear flow dynamic arguments. Model simulation results are in agreement with in vivo wound healing data. Clinically convenient optimal EGF therapeutic regimens were determined using model simulations.