The ultimate goal of these studies is to provide a clear understanding of the changes in lens membrane transport and permeability that contribute to the development of cataract. Cataract, the third most common cause of blindness in the USA, presently is treated only by surgery. This study will aid in the development of medical therapy of cataract. Lens membrane transport and permeability properties following stress or damage (e.g. oxidation and osmotic stress) will be evaluated by electrophysiological and isotope flux methods. The ability of membranes to tolerate and/or recover from transient damage will also be evaluated. Changes in lens electrolyte balance are determined by atomic absorption spectrophotometry, and ATPase kinetics by biochemical assay. The unique impact of elevated lens calcium on membranes will be studied. Lens calcium distribution and movement will be evaluated using 45Ca flux techniques, net calcium uptake, and calcium-sensitive microelectrodes. The interaction of calcium with intracellular macromolecules will be probed with use of a novel lens homogenate flux chamber and calcium macroelectrode experiments. Microregional changes in electrolyte balance in experimental cataract will be determined using graphite furnace atomic absorption spectrophotometry. Electrolyte changes will be compared and contrasted to protein profiles obtained by HPLC. The mechanism of """"""""sealing"""""""" of damaged loci within the lens from undamaged lens cells will be investigated. The pathophysiology of an inherited sheep cataract will be described in terms of electrolyte balance, membrane integrity and microregional analysis. Our data will be correlated with biochemical studies being undertaken in New Zealand. Most of these studies will be performed on animal lenses, but where feasible, we will utilize human lenses obtained either from eye bank eyes or following scheduled cataract surgery.
