The contribution of glycation to cataract formation in diabetes.

BACKGROUND

Despite extensive research, the mechanisms responsible for Type II diabetic cataract formation are still unknown. Recent data have favored non-enzymatic glycation. However, the pathways by which hyperglycemia leads to cataract are still unknown. Two possible routes were explored; modification of the lens proteins leading to Advanced Glycation Endproduct (AGE) formation and modification of the ATPase pumps leading to osmotic stress.

METHODS

The extent of AGE formation was monitored in fetal bovine eyes using non-tryptophan fluorescence. The amount of carbohydrate bound the proteins was measured after reduction with radiolabelled sodium borohydride. Secondary structure estimations were performed by analysis of data obtained using circular dichroism. The effect of glycation on the Na, K-ATPase ion pumps was investigated by comparing the uptake of radioactive 86Rb in the presence of high concentrations of glucose and fructose.

RESULTS

These studies were aimed at determining which of these mechanisms is the more likely route for cataract formation. The first mechanism was examined using two approaches. Firstly, by investigating the effects of increased glucose on the secondary and tertiary structure of lens proteins. Detailed analysis of the structures of the lens proteins in the presence of 200 mM glucose revealed that only alpha-crystallin was slightly affected. More important, however, this change did not lead to any significant aggregation. The second approach involved comparing the mechanism of action and possible benefits of anti-glycating agents.

CONCLUSION

It is concluded that Type II diabetes cataracts are unlikely to arise as a result of AGE formation, but rather they form because of disruption of the cells, as a result of osmotic stress, brought about by glycation of the ion pumps.