Corneal growth factors: a new generation of ophthalmic pharmaceuticals

Several of the known growth factors either have an effect on corneal tissues or can be isolated from them. Both epidermal growth factor (EGF) and fibroblast growth factor (FGF) stimulate the proliferation of corneal epithelium, keratocytes, and endothelium. Compared to FGF, EGF is more potent in stimulating the growth of endothelial cells; it also increases the tensile strength of corneal stromal wounds. The corneal epithelium produces an angiogenic growth factor as well as a neuronotrophic growth factor. Insulin-like growth factor stimulates the growth of keratocytes and enhances the effect of EGF on the corneal endothelium. Mesodermal growth factor stimulates the proliferation of keratocytes and increases the rate of healing of damaged corneal endothelial cells. It is evident that growth factors have many potential clinical applications especially in accelerating corneal wound repair after surgery, chemical burns, or ulcers, and in increasing the numbers of corneal endothelial cells in aging and diseased corneas, as well as in donor corneas to be used for transplantation. Several parameters require evaluation, e.g. the dose, concentration, combination and formulation, exposure time, receptor affinity, and tissue interdependence of the growth factor(s), as well as the variability in patient response and severity of disease and/or injury. Investigations are also needed for the development of effective delivery systems and for determining whether growth factors are specific and safe in humans. Growth factors are emerging as a new generation of ophthalmic pharmaceuticals, and they will soon be integrated into the advancing practice of ophthalmic surgery and medicine.