SPECTROSCOPIC AND RELATED STUDIES ON LENS MEMBRANE LIPID

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Description (from abstract): The pronounced effects of aging on the levels of oxidation and composition of human lens membranes have been studied extensively in our research. Publications by the investigator and others indicate that plasma membranes from cataractous tissues exhibit higher levels of oxidation as well as elevated sphingomyelin and cholesterol contents. Yet, the specific molecular events that relate these alterations to the process of opacification or cataractogenesis remain unclear. As cataracts are formed, lens transparency is lost due primarily to light scattering. The thrust of this project is to assess, at the molecular level, the fundamental reasons for which changes in lens membranes may result in the enhancement of light scattering. Specifically, the investigator proposes to quantify the contribution of light scattering that results from the tighter packing of the hydrocarbon chains in membranes with increased oxidation levels and sphingolipid content. Secondly, he will test the possible enhancement of Mie and Rayleigh scattering due to greater binding efficiency of a-crystallin to deranged membranes. Thirdly, the relative arnount of light scattering caused by the increase in permeability of calcium ions will be explored. Calcium ions, among many mechanisms, could lead to the scattering of light by either binding to lipids via a structural or syncretic (excluding water) mechanism or by forming protein condensates. Finally, the formation of oxidized condensates containing lipids and a mixture of crystallins that may dislodge from the membrane network will be investigated. These aggregates may serve as focal opacities that increase the contribution of Mie scattering to the overall loss of transparency with age and cataract. The ability to monitor, simultaneously and in situ, light scattering levels along with lipid and protein structure will enable us to identify specific molecular alterations and estimate their contribution to the overall level of light scattering in cataractous tissues. An understanding of these alterations will facilitate the development of therapies to prevent or perhaps even reverse these changes.