Corneal transplantation is the oldest and arguably, the most successful form of organ transplantation. In the United States alone, over 40,000 corneal transplants are performed annually. In spite of the high success rate of keratoplasty, approximately 10% of the corneal grafts will fail due to immunological rejection. Thus, developing new and more effective strategies for preventing immunological rejection of corneal allografts could have an enormous impact on the preservation and restoration of vision in large number of individuals. The long range goal of the present research project is to develop, evaluate, and characterize novel strategies for preventing the induction of corneal graft rejection and for reducing the risk of late graft rejection in hosts bearing long term clear corneal grafts. The immediate specific aims of this project are: (l) utilization of ultraviolet B irradiation (UVB) to render corneal grafts nonimmunogenic and possibly tolerogenic; (2) utilization of antibodies against cell adhesion molecules as a method for preventing immunological effector cell function and for inducing immunological tolerance; (3) use of hyperbaric O2 treatment as a method for reducing the immunogenicity of corneal grafts; (4) determine the effect of induced class II MHC antigen expression on the survival of previously clear corneal grafts; (5) evaluate the immunogenic potential of sequential corneal allografts (i.e., """"""""silent stimulation"""""""" of delayed type hypersensitivity); and (6) to determine the specific role of spontaneous corneal neovascularization on corneal allograft survival. The majority of these investigations will be addressed using a mouse model of penetrating keratoplasty. The results from these investigations should provide important insights into the immunobiology of corneal allografts and the feasibility of specific immunological strategies for promoting corneal allograft survival.
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