TARGETING OF IMMUNOTOXINS TO LENS EPITHELIAL CELLS

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A major problem in treatment of cataracts by extracapsular lens replacement is the subsequent loss of vision due to "secondary cataract" formation, or posterior capsule opacification. The economic impact of cataract surgery in the United States has been estimated to be $3.5 billion per year, and may reach $5.5 billion by the year 2008. Up to 50% of patients may develop secondary cataracts. The major cause of this problem is a regrowth of lens epithelial cells that cannot easily be removed during 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 against fibroblasts in Phase I. 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, e.g., in the monitoring of cell surface changes accompanying differentiation, growth, aging and cataract formation in the ocular lens.