Treatment of proliferative vitreoretinopathy by inhibition of migration

DESCRIPTION (provided by applicant): Proliferative vitreoretinopathy (PVR) is the principal cause of failed retinal detachment surgery. PVR is characterized by the migration and proliferation of retinal pigment cells, fibroblasts, glial cells, and inflammatory cells on or beneath the retina or in the vitreous cavity. This leads to the formation of contractile cellular membranes which cause retinal detachment. Attempts to treat PVR have involved the use of antimetabolites and steroids. None of these options have come into routine clinical use and current interventions are limited to surgical treatment. While inhibition of cell proliferation has been the focus of the development of drugs to treat PVR, the possibility that cell migration, which plays as important of a role, would be another potential target. We have developed a small molecular weight protein (LD22-4) that inhibits the migration of a number of different cell types in vitro and in vivo. Because of the importance of cell migration in the development of PVR and the proven effectiveness of LD22-4 in vivo, we performed studies of the effect of the protein in a rabbit model of PVR. The results clearly showed that LD22-4 inhibited the development of PVR in each animal that received the protein. Based on these considerations, we propose a more extensive evaluation of the effects of LD22-4 on PVR. The Phase I project will assess dose titration analysis to establish effective doses for maximum inhibition of PVR. These results will provide the basis for the eventual use of LD22-4 in the treatment of PVR. PUBLIC HEALTH RELEVANCE: Proliferative vitreoretinopathy (PVR) is the principal cause of failed retinal detachment surgery. Attempts to treat PVR with drugs have been unsuccessful and current interventions are limited to surgical treatment. We have developed a small molecule (LD22-4) that inhibits the migration of cells that promote PVR. We have shown that LD22-4 inhibits the development of PVR in animal models. The project outlined in this proposal tests the effectiveness of this newly developed protein that targets PVR in a unique manner, the inhibition of cell migration, offering additional hope to patients with this disease.