Polyol pathway: A possible mechanism of diabetes complications in the eye

Abstract

In complex diseases such as diabetes mellitus, the causative agents include various serum factors such as glucose, aldose reductase, oxygen-free radicals, advanced glycation end products, protein kinase-C and growth factors. The polyol pathway is a pathway of glucose metabolism and is regarded as an important element in the pathogenesis of refractive changes, cataract formation and diabetic retinopathy in individuals with diabetes mellitus. The focus of this review is on the role of the polyol pathway in the pathogenesis of diabetic complications in the eye. The first enzyme (aldose reductase) in the polyol pathway reduces glucose to sorbitol. The second enzyme (sorbitol dehydrogenase) converts sorbitol to fructose. The accumulation of sorbitol and fructose in the crystalline lens and retina leads to the generation of oxidative stress. Oxidative stress is the imbalance between levels of reactive oxygen species and the antioxidant defence in a biological system, and it results in tissue damage. How hyperglycaemia leads to oxidative stress is not clear but could be through a combination of increased levels of reactive oxygen species and decreased capacity of the cellular antioxidant system. Oxidative stress causes the development of diabetic complications that are seen clinically.