The goal of the proposed research is to develop a pharmacologic therapy for the prevention of proliferative vitreoretinopathy (PVR), the most common cause of failure of retinal detachment surgery. In the past grant period we have screened drugs for efficacy in rabbit model of PVR. Daunomycin proved to be the drug of choice and is currently undergoing clinical trail in Europe. However, the therapeutic window of daunomycin is narrow. Additional research is necessary to provide improved drug delivery and to increase efficacy through combination with other drugs. The pathogenesis of PVR involves a sequence of wound healing processing gone awry, each of which is a target for intervention. Thus suppression of post-surgical inflammation, blood-ocular barrier breakdown and attraction and migration of cells into the vitreous by anti-inflammatory and anti-chemotactic agents in combination with daunomycin could increase its efficacy and reduce its toxicity. The proposed studies will evaluate combinations of anti- inflammatory and anti-chemotactic drugs with daunomycin in rabbit models of PVR characterized by a strong inflammatory or chemotactic response. The toxicity of the most efficacious combination will be evaluated in primates. The results of these studies is of importance for the rational design of effective pharmacologic prevention of PVR in man.
