There is a clinical need for an agent which stimulates healing of corneal wounds such as chronic corneal epithelial defects, stromal incisions, and endothelial cell injuries. Our long-term goal is to evaluate the effectiveness of biosynthetic human epidermal growth factor (h-EGF) produced by genetically engineered yeast to accelerate healing of corneal wounds. Our initial results demonstrate that h-EGF alone or in combination with dexamethasone is a potent and rapid accelerator of epithelial regeneration and stromal incision healing. 1. To perform dose-response curves and to determine time course of wound healing using h-EGF in eye drops given with and without steroids for stimulating (a) epithelial regeneration and (b) healing totally penetrating stromal incisions in rabbits. 2. To evaluate the effectiveness of combinations of h-EGF with other agents, e.g. ascorbate and trans-retinoic acid for accelerating the rate of (a) epithelial regeneration following abrasion or mild thermal or mild chemical burns (acid, base solvent) and (b) healing totally penetrating stromal incisions in rabbits. 3. To evaluate the clinical effectiveness of h-EGF for stimulating (a) epithelial regeneration of transplanted cornea denuded of epithelium and (b) healing of stromal incisions of postoperative penetrating keratoplasty patients. 4. To biochemically characterize EGF-receptor of human corneal endothelial cells. 5. To test the ability of h-EGF to stimulate mitosis of human corneal endothelial cells in organ culture. 6. To test the ability of h-EGF to promote endothelial cell viability in commercial eye bank medium (M-K). 7. To synthesize and evaluate the binding and biological activity of macromolecular h-EGF conjugates on human corneal endothelial cells in organ culture. 8. To evaluate the in vivo effectiveness for stimulating healing of endothelial injuries to primate corneas using bioactive macromolecular EGF-conjugates designed to slowly exit the anterior chamber. These experiments will further our understanding of h-EGF action on corneal wound healing and should they prove successful, provide new concepts in clinical management corneal injuries.
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