Our long term objectives are to determine the biophysical basis of cataract formation, and to identify chemical means for the inhibition or reversal of cataract both in mammalian systems and in humans. To achieve these objectives we present briefly below the specific aims of the proposed research. 1. To determine the microscopic structure and composition of the molecular aggregates responsible for the scattering of light and opacification of the lens in cataract. 2. To identify reagents which can inhibit or reverse cataract formation. These reagents will first be evaluated for their effectiveness in suppressing phase separation cataract using concentrated solutions of purified lens crystallins, lens cytoplasmic homogenates, and then whole mammalian lenses in vitro. The reagents will also be tested for their effectiveness in suppressing cataracts produced by known cataractogenic agents such as oxidizing agents, high salt, calcium and sugars acting on the systems mentioned above. 3. To develop the method of quaielastic light scattering spectroscopy for clinical use in vivo, in order to detect non-invasively very early stages of cataract development. 4. To conduct initial tests of the ability of the instrument, which is mentioned in (3), to provide a new, non-invasive method for the quantitative characterization of the viscoelastic properties of the collagen fiber network in both normal corneal stroma and in corneas undergoing early pathological changes. 5. To use high resolution nuclear magnetic resonance measurements of chemical shifts and relaxation times to study: (a) Differences in composition and environment of amino acid side chains of individual purified lens protein fractions. (b) The degree of cross linking produced by cataract inhibiting reagents. (c) The relative proportions of protein-rich and protein-poor phase along the coezistence curve for protein phase separation.
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