PVR\AN IMMUNOPHARMACOLOGICAL APPROACH TO TREATMENT

PROLIFERATIVE VITREORETINOPATHY (PVR) IS A POTENTIALLY BLINDING DISEASE CAUSED BY THE MIGRATION INTO AND SUBSEQUENT PROLIFERATION OF RETINAL PIGMENTED EPITHELIAL CELLS (RPE), GLIAL CELLS, FIBROBLASTS AND MACROPHAGES IN THE VITREOUS CAVITY. THIS INVASION OF THE VITREOUS CAN RESULT FROM DISEASE OR TRAUMA. GROWTH AND DIFFERENTIATION OF THE INVADING CELLS CAN EVENTUALLY LEAD TO A TRACTIONAL DISTORTION AND DETACHMENT OF THE RETINA. THE RESEARCH SEEKS TO DEVELOP MONOCLONAL ANTIBODY-BASED IMMUNOTOXINS SPECIFIC FOR THESE OFFENDING CELLS. THE RESULTING IMMUNOTOXIN(S) COULD BE USED AT THE TIME OF VITRIOL-RETINAL SURGERY AS A PREVENTIVE, OR AS A TREATMENT TO PREVENT FURTHER GROWTH OF THE INVADING CELLS, AND HENCE ELIMINATE THE NEED FOR VITRIOL RETINAL SURGERY, OR AS AN ADJUNCT TO SURGERY. IT WOULD BE PARTICULARLY USEFUL IN CASES OF POSTERIOR SEGMENT PENETRATING INJURY, WHICH IS A MAJOR CAUSE OF PVR. THE MAJOR OBJECTIVES OF PHASE I ARE TO PREPARE CELL SPECIFIC MONOCLONAL ANTIBODIES, TO DETERMINE THEIR POTENTIAL AS IMMUNOTOXINS IN VITRO ASSAYS, AND TO ESTABLISH AN IN VITRO MODEL FOR PVR. THE OBJECTIVE OF THE PHASE II WOULD BE TO TEST THESE IMMUNOTOXINS IN VIVO FOR EFFICACY AND TOXICITY.