The refractive homogeneity of a high protein gel-like lens depends on the specific crystallins interaction and supra-molecular complex formation and organization. The packing arrangements of these protein complexes in relation to cytoskeletal structure are determined by the interactions of lens proteins and conditions in the surrounding milieu. Due to the continuous growth, the lens fibers developed at different ages are heterogeneous with regards to composition and content. Analyses of successive concentric lens fractions from individual human lenses indicate differences in membrane-protein interactions in various lens regions. Knowledge on the composition and dynamics of these regions provide the basis to delineate the effects of aging and fiber development that are required to maintain normal lens funciton and cell to cell communication. Initial studies on lens lipids indicate that 1) the outer cortex, inner cortex and nucleus of human lenses are characterized by distinctively different lipids, and 2) the lipid and protein polypeptides in various lens regions change with lens age and a significant nuclear protein insolubilization occurred during the 4th to 5th decade of normal lens growth. Comparison of the soluble and insoluble polypeptides by electrophoretic and chromatofocusing isolation and sequence analyses will be performed to reveal those altered mechanisms of protein insolubilization involved in nuclear sclerosis and/or presbyopia. Results on the regional differences in these polypeptides will distinguish molecular changes due to aging from those due to fiber development. Analyses of lipid obtained from lenses of various age groups will provide information on the age-related changes in lipid metabolism and accumulation during fiber development that can eventually lead to opacification. Isolation and characterization of fiber membranes from cataractous lens will be carried out to elucidate the modified crystallin and membrane interactions responsible for the observed refractive inhomogeneity in senile nuclear cataracts.
