Advanced glycation endproducts in human diabetic and non-diabetic cataractous lenses.

BACKGROUND

Advanced glycation endproduct (AGE) formation is thought to contribute to aging and cataract formation in the lens. In this study, we evaluated AGE immunoreactivity in human diabetic (n=14) and nondiabetic (n=31) cataractous lenses in relation to high-molecular-weight (HMW) protein content, which is believed to contribute to the onset of cataract.

METHODS

AGE immunoreactivity was detected in alkali-soluble individual lens samples. Competitive ELISA with polyclonal anti-AGE antibody was performed to estimate AGEs. SDS-PAGE was used to detect changes in lens protein composition on the basis of molecular size.

RESULTS

Regression analysis of data from nondiabetic lenses showed a significant correlation between lens AGE content and patient age (r=0.665, P<0.001). The curve exhibited exponential regression ( y=0.272.e(0.025x)). The level of nonspecified AGEs measured in diabetic lenses showed an overall increase compared with nondiabetic lenses (4.03+/-1.85 vs 1.78+/-0.71 AU/mg protein, P<0.0078). SDS-PAGE showed the occurrence of HMW proteins in both diabetic and nondiabetic lens samples. However, in diabetic patients, who had a higher level of AGEs, a significantly higher proportion of HMW proteins was also observed. The levels of AGE and percent of HMW aggregates showed a very significant correlation ( r=0.68, P<0.007) in the diabetic group, whereas in nondiabetics the correlation, although positive, did not reach statistical significance.

CONCLUSION

The AGE distribution, with a higher proportion in the samples of lenses rich in HMW aggregates, corroborates the hypothesis that the advanced glycation process might have a role in degenerative changes in eye lens, which in diabetic patients occur vigorously and much earlier than in those without diabetes.