ASCORBIC ACID GLYCATION AND SENILE CATARACT FORMATION

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In the last two decades, major advances have been made in understanding lens protein structure and lens crystallin gene expression. We are obtaining increasingly detailed knowledge about cataracts in mice and rats, but the mechanisms that result in age-onset cataract in humans, still remains elusive. Many in vitro experiments mimic features seen in these cataracts, but there is little in the way of confirmation that these reactions are significant, or causal in the process. Our laboratory has been investigating the role of advanced glycation endproducts in this process. Specifically, we are investigating whether the oxidation products of ascorbic acid are responsible for the protein-protein crosslinks, chromophores and fluorophores seen in these lenses. In the work described here we hope to find common structures between calf lens proteins ascorbylated in vitro and the protein modifications seen in aged human lenses and cataracts obtained from India. A scheme for the isolation of these modifications from proteins is presented. Also, the common compounds will be identified by mass spectrometry, their spectral properties and proton NMR. In addition, we intend to study the degradation of ascorbic acid in cultured human lenses, and to measure the effect of external agents to bring about the oxidation and incorporation of ascorbic acid into the proteins in these lenses.