Proliferative vitreoretinopathy (PVR) is the principal cause of failed retinal reattachment surgery. PVR is characterized by the migration and proliferation of retinal pigment epithelial cells (RPE), glial cells, fibroblasts, and other cell types in the vitreous cavity or on and beneath the retina. This leads to neo-membrane formation, contraction, and retinal detachment. We have designed ribozymes targeting PCNA mRNA that are capable of inhibiting cellular proliferation. PCNA is a critical cell cycle division factor in all cell types. Delivery of these therapeutic ribozymes to the retina should transiently inhibit proliferation of a broad range of cells. This study will examine the effect of ribozyme inhibition of proliferation on development of PVR in a rabbit dispase model. These results will provide the preclinical foundation for a clinical test of the efficacy of this anti-proliferative therapy in the treatment of PVR. PROPOSED COMMERCIAL APPLICATION Immusol, Inc plans to commercially develop chimeric ribozymes for the treatment of proliferative vitreoretinopathy.