SBIR-STTR Award

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.

Proliferative vitreoretinopathy (PVR) is the principal cause of failed retinal reattachment surgery. Uncontrolled proliferation can lead to scar formation in the eye following surgical procedures. The resulting scar can result in visual impairment. We have designed ribozymes targeting PCNA mRNA that are capable of inhibiting cellular proliferation. In the Phase I portion of this work, we demonstrated that the PCNA targeted ribozymes were able to recognize and cleave the rabbit PCNA substrate. The ribozymes could be delivered into a variety of cell types involved in PVR development. Delivery of the ribozymes into the rabbit eye effectively inhibited the development of PVR in the rabbit dispase model. In this portion of the proposal, an optimized formulation for opthalmic use will be tested. The toxicity profile of the PCNA targeted ribozymes in the rabbit and porcine eye will be determined. These results will provide the foundation for development of this anti-proliferative drug for the treatment of PVR and for use in other surgical procedures in the eye with adverse outcomes due to ocular scarring.