Racemization in human lens: evidence of rapid insolubilization of specific polypeptides in cataract formation.

Abstract

After early life, the dry weight of normal human lenses increases at a relatively constant rate with time. Transformation from soluble to insoluble material appeared to occur at a comparable rate, resulting in a constant amount of soluble material. In cataract the insolubilization rate was accelerated. These observations were supported by determination of D-aspartic acid/L-aspartic acid ratios. The abundance of D-aspartic acid increased with aging at a constant rate in the insoluble fraction of normal lenses but did not change in the soluble fraction. In cataractous lenses there was a significant decrease in the ratio in the insoluble fraction. Examination of polypeptides isolated from reduced and alkylated soluble and insoluble cataractous lens protein and other data suggested the following additional conclusions: the 10,000 dalton polypeptide in the insoluble fraction was derived in part from degradation of an already insoluble precursor; and the lowered abundance of D-aspartic acid in the insoluble fraction of cataractous lenses was primarily due to the rapid insolubilization of the 43,000 and 20,000 dalton range components.