Genetic analysis of aldose reductase in diabetic complications.

Diabetes Mellitus is an increasing concern, worldwide in terms of health. Long-term diabetes often leads to secondary diseases such as cataract, retinopathy, neuropathy, nephropathy, and cardiovascular diseases. The enzyme aldose reductase (AR) has been implicated in the pathogenesis of some of these diseases and inhibitors of AR (ARIs) were effective in preventing some of the diabetic complications in animal models. However, clinical trials of these drugs were disappointing, casting doubt on the role of AR in these diseases. This review focuses on the recent studies using transgenic and gene knockout mice to analyze the role of AR in diabetic cataract and neuropathy. These studies clearly demonstrated that AR is crucial to the pathogenesis of these diseases, and that the mechanism leading to diabetic cataract may be different from that which causes diabetic neuropathy. A number of studies showed that there is a correlation between AR gene markers and susceptibility to develop complications among diabetic patients, suggesting that AR is also involved in the pathogenesis of diabetic complications in human. Together, these genetic studies strongly indicate that AR is an important target for the prevention of diabetic complications in human. This may provide impetus to develop more effective ARIs and to conduct better-designed clinical trials for ARIs in the prevention and treatment of these diseases.