TARGETING OF IMMUNOTOXINS TO LENS EPITHELIAL CELLS

A MAJOR PROBLEM IN THE TREATMENT OF CATARACTS BY EXTRACAPSULAR LENS REPLACEMENT IS THE SUBSEQUENT LOSS OF VISION DUE TO SECONDARY CATARACT FORMATION. UP TO 50 PERCENT OF THESE PATIENTS MAY DEVELOP SECONDARY CATARACTS. THE MAJOR CAUSE OF THIS PROBLEM IS A REGROWTH OF LENS EPITHELIAL CELLS THAT CANNOT EASILY BE REMOVED CURING CATARACT SURGERY AND REMAIN ATTACHED TO THE LENS CAPSULE. THE OVERALL AIM OF THIS PROJECT IS THE DEVELOPMENT OF AN IMMUNOTOXIN DIRECTED SPECIFICALLY TO LENS EPITHELIAL CELLS. SUCH A TOXIN WILL BE ADDED TO THE EYE PERFUSATE DURING SURGERY AND WILL HOPEFULLY DESTROY LENS EPITHELIAL CELLS WITHOUT HARMING ANY OTHER OCULAR CELLS. THE AIM OF PHASE I IS TO PRODUCE MONOCLONAL ANTIBODIES REACTIVE WITH THE CELL SURFACE OF RABBIT LENS EPITHELIAL CELLS BUT NOT REACTIVE WITH RABBIT OCULAR FIBROBLASTS. MICE WILL BE IMMUNIZED WITH RABBIT LENS EPITHELIAL CELLS, AND HYBRIDOMAS WILL BE PRODUCED. POSITIVE HYBRIDOMAS WILL BE SELECTED BY SCREENING AGAINST RABBIT LENS EPITHELIAL CELLS AND FIBROBLASTS. ANTIBODIES SPECIFIC TO HUMAN EPITHELIAL CELLS WILL BE DEVELOPED AND USED IN PHASE II. MONOCLONAL ANTIBODIES TO LENS EPITHELIAL CELLS WILL ALSO HAVE A BROAD RANGE OF USES IN BIOMEDICAL RESEARCH.