The proposed research program will establish the sequential steps in the development of lens transparency. The research will be quantitative study of lens cell growth and development using computer aided 3-dimensional reconstructions to define relationships between structural and chemical parameters and to analyze: dimensions of transparent and opaque domains at different stages of development; concentrations and spatial distributions of Ca, Mg, P, S, H, K, Na, Cl; and areas of surfaces labeled with cholesterol and phospholipid probes. Previous research has led to the identification of reversible pathways for cellular restructuring during the early stages of cataract development. I suggest that these mechanisms of restructuring do not appear spontaneously when lens cells are exposed to cataractous conditions, but exist in normal cells before the onset of cataracts and function in the normal development and maintenance of lens transparency. Thus, early stages of cataract restructuring may be understood by studying the mechanisms controlling normal cell restructuring, quite apart from pathological conditions. The study of these mechanisms will use 3-dimensional computer aided imaging to analyze relationships between structure and composition of developing lens cells. New methods of light microspectrometry and LASER/NMR instrumentation will be developed for data collection. I propose to use the information gained from this study as the basis for new methods for prevention of opacification and maintenance of transparency in animal and human eyes.
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