Lens crystallins are evolutionarily conservative proteins that are the primary structural constituents of the lens. The focus of work in this laboratory is oriented toward: 1) increased understanding of the structural attributes of these proteins which contribute to their fitness to serve as components of a transparent tissue and 2) elucidation of the mechanisms whereby changes in the composition of lens crystallins or aging-related modification of these long- lived proteins can contribute to opacification of the lens. The studies on zeta-crystallin, a lens protein, thus far found only in guinea pigs, have yielded several significant new findings. We now know that this protein is related to alcohol dehydrogenase and thus apparently represents the first reported example of a taxon- specific crystallin in a mammal in which an enzyme has been adopted by the lens as a structural protein. Since zeta-crystallin is not present in the animals homozygous for the congenital cataract trait, it is possible that the lack of zeta may be the initiating factor in the formation of the cataract. Such a situation would provide a unique system for studying the function of an individual crystallin as part of the transparent protein matrix in the lens. Studies on protein synthesis in the cataract lenses reveal significant synthesis of a protein which is not detected in normal lenses. Use of an antibody raised against a synthetic peptide from zeta-crystallin reveals that this second protein is related to zeta. It has been demonstrated that both inhibition of the glutathione redox cycle with BCNU or decreasing lens ATP through use of 2- deoxyglucose can potentiate the oxidative modification of crystallins in cultured rat lenses exposed to hydrogen peroxide.
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