Diabetic retinopathy is the most common microvascular complication of diabetes and the most severe of diabetic ocular complications. This review describes
retinal changes at different stages of
diabetic retinopathy and risk factors associated with this devastating disease. Special attention is focused on
aldose reductase, the first
enzyme of the
sorbitol pathway of
glucose metabolism. The current knowledge on the
enzyme localization in the retina, and the role for increased
aldose reductase activity in
retinal capillary cell loss and formation of acellular capillaries, capillary basement membrane thickening, increased vascular permeability and disruption of blood-retinal barrier, and increased leukocyte adhesion to endothelial cells associated with early
diabetic retinopathy, as well as neovascularization associated with advanced (proliferative)
diabetic retinopathy, gained through the experimental studies in animal models of diabetes and
galactose feeding, is described in detail. The review also analyzes the potential mechanisms underlying
aldose reductase involvement in pathogenesis of
diabetic retinopathy, and discusses interactions between
aldose reductase and other pathogenetic factors such as formation of
advanced glycation end-products, oxidative-nitrosative stress,
protein kinase C,
mitogen-activated protein kinase, and
poly(ADP-ribose) polymerase activations,
inflammation, and
growth factor imbalances. A detailed analysis of clinical
diabetic retinopathy trials of
aldose reductase inhibitors is also provided.