The work described int his grant is based on the premise that oxidative insult is an initiating or early event in the development of maturity onset cataract. The grant requests support for 3 new initiatives based on the above premise. (1) The use of mixed function oxidation reactions with a specific lens protein, alpha crystallin, to elucidate covalent non-disulfide linkages and other modifications including alteration in the vicinity of the phosphoserine positions of the B chain. The work will lead to elucidation of similar modifications which arise during the development o maturity onset cataract. (2) An examination of the impact of oxidation on lens epithelial cell DNA with respect to damage, repair and mutation. The work will attempt to approach the question of whether oxidative damage to the DNA can lead to maturity onset cataract. (3) The development of powerful, physiologically compatible reductants. The work will produce thioredoxin peptide analogs which, in theory, should prevent or repair oxidative damage to the lens. The analogs will be tested in cell and organ culture systems to ascertain whether they are effective.
