The processes of aging in the human lens have been difficult to study because the mechanisms by which alterations occur in the lens are not known. The proteins in the lens undergo distinctive changes in their charge but the cause of these modifications and the relationship between these alterations and cataract formation is not established. One way of investigating these changes is to study the individual proteins in vitro and determine how modifications affect the structure and interactions of these crystallin proteins with other proteins. One of the major groups of proteins in the lens is gamma-crystallin. One of the gamma- crystallin genes has been stably integrated into mouse L-cells. By using the gamma-crystallin expressed in the mouse cells, studies of the alteration of the human protein in an oxidation system have been done. The microheterogeneity and the shift of the protein to more acidic forms that are observed in the aging human lens have been observed with the crystallin in vitro. It would appear that the many of the alterations that are seen in the gamma-crystallin in the nucleus of the human lens can be mimicked with a mixed function oxidation system on isolated proteins. Thus, many of the changes that have been reported on aging in the human lens may be the result of oxidative damage to the components of the lens. Additionally, work has progressed on the calcium binding proteins of the lens. These proteins, called annexins, may play a major role in development and differentiation in the lens. At least two of the major calcium binding proteins in the lens have been shown to be glycosylated. The addition of sugar residues on these proteins may indicate there is another level of control which the cell has for these very important proteins.

National Institute of Health (NIH)
National Eye Institute (NEI)
Intramural Research (Z01)
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U.S. National Eye Institute
United States
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McGowan, M H; Russell, P; Carper, D A et al. (1999) Na+, K+-ATPase inhibitors down-regulate gene expression of the intracellular signaling protein 14-3-3 in rat lens. J Pharmacol Exp Ther 289:1559-63