The formation of
sugar-
cataracts has been hypothesized to involve the nonenzymatic glycosylation, sulfhydryl oxidation, and aggregation of
lens proteins. Cataractous
lenses of diabetic and galactosemic rats were analyzed for
glycosylated lysine residues in
crystallins. A five- and a ten-fold increase in
glycosylated lysine residues was measured in
galactose and diabetic
cataracts, respectively. The modification was predominant in the insoluble fraction of the lens homogenate. The
proteins were further examined for the presence of
disulfide bonds and high molecular weight aggregates. After careful disruption of the lens in a
nitrogen environment, a cloudy
solution was obtained from cataractous
lenses whereas a clear
solution was obtained from normal
lenses. The absorbance at 550 nm of the
solution of both the galactosemic and the diabetic
cataracts could be decreased by approximately 50% with the addition of
dithioerythritol (50 mM). The presence of high molecular weight aggregates was ascertained by
sucrose gradient centrifugation and gel filtration chromatography. The
proteins were heterogenous in size and showed a mol wt range of 36 to greater than 176 million daltons. Treatment with
dithioerythritol induced a marked decrease in the amount of high molecular weight
proteins. These data suggest that
sugar cataracts of experimental animals have, in common with human
cataracts, the presence of high molecular weight aggregates which are in part linked by
disulfide bonds.