During aging and cataractogenesis, lens proteins undergo a number of chemical and physical modifications, namely, aggregation, pigmentation, and increased production of insoluble proteins. It is believed that conformational change is associated with these processes. Investigations to date have suggested that light, calcium ion, sugar molecules (in diabetic cataract), etc. are among the causative factors for this protein modification which may eventually lead to cataract formation.
Our aims are: 1. To gain insight into the molecular features of normal lens proteins and to understand the cause of their modifications. We will investigate: (a) the molecular structure of the subunits of alpha- and beta crystallins; and (b) the nature of interactions among lens crystallins. 2. To describe changes in the molecular features upon application of the following cataractogenic agents: (a) light; (b) active species of oxygen; (c) sugar, metabolites of sugar, and glycosylation; (d) Ca2+; and (e) carbamylation. 3. To study intact lenses in a similar manner. For model studies, bovine lenses will be used. Studies will be extended to human lenses, old and young, normal and cataractous (as available). Lens crystallin will be isolated routinely by gel chromatography and characterized by HPLC. Appropriate chemical, biochemical, hydrodynamic, and spectroscopic techniques will be used to monitor conformational aspects and their changes. These include gel chromatography, gel electrophoresis, sedimentation equilibrium by ultracentrifuge, fluorescence, phosphorescence, circular dichroism and Raman resonance spectroscopy.
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