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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 AGE lens content and patient age (r=0.665, p<0.001). The curve exhibited exponential regression (y=0.272&#61655; e0.025x). The level of nonspecified AGEs measured in diabetic lenses showed an overall increase as compared to nondiabetic lenses (4.03&#61617; 1.85 vs 1.78&#61617; 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 percentage 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 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 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.

Advanced glycation; Diabetes; Lens; Cataract

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