The structures and functions of the major lens proteins, the crystallins, are being analyze with respect to the roles they play in the establishment and maintenance of the transparency of the lens. An understanding of what crystllins are and how they function in the normal lens is essential if we are to understand the chaperone-like activity of alpha-crystallin. Alpha-Crystallin is a major protein of the lenses of all vertebrates and was shown earlier in test tube experiments to be able to prevent the aggregation of denaturing proteins. We have now developed data to support the hypothesis that this activity is physiologically relevant. Using complex mixture of lens proteins and intact monkey lenses, it was demonstrated that under heat stress alpha-crystallin forms soluble complexes with denaturing proteins thereby preventing their uncontrolled aggregation and insolubilization, a process that would produce light scatter and opacity within the lens. The soluble complexes formed are very similar to the heavy molecular wright (HMW)-soluble protein fraction that is known to increase with age in human lenses. We believe, in fact, that the HMW fraction is the product of the endogenous chaperone-like activity of alpha-crystallin and that this activity represents an important protective mechanism in vivo. In other results under this project, additional evidence has been obtained to support the hypothesis that elevated pyridine nucleotides associated with certain enzyme- crystallins confer selective benefit to the lens, probably by augmenting antioxidant defenses. Further, testing of potential anticataract agents in a lens organ culture system has continued, and initial efforts have been made to introduce foreign genes into the lens and other tissues of the anterior chamber using adenovirus vectors.
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