Aldose reductase in the diabetic eye. XLIII Edward Jackson memorial lecture

In diabetic cataracts aldose reductase initiates the cataractous process by converting glucose to sorbitol. The ensuing osmotic change, caused by sorbitol accumulation, adversely affects the lens permeability barrier so that the distribution within the lens of electrolytes, amino acids, and myo-inositol becomes grossly altered. These changes affect lens viability resulting in opacification. That aldose reductase triggers the process is shown by the fact that several structurally unrelated aldose reductase inhibitors prevent cataracts from occurring. Aldose reductase is also implicated in diabetic retinopathy and keratopathy. Aldose reductase functions in the retinal capillary pericytes, the cells first affected in microvascular abnormalities in diabetes. Additionally, retinal capillary basement membrane thickening can be prevented by aldose reductase inhibitors. Clinical trials are underway to determine the efficacy and safety of aldose reductase inhibitors in treatment of diabetic retinopathy.