Aldose Reductase Aldose reductase converts sugars into their alcohols.

For example, glucose is converted to sorbitol and galactose is converted to galactitol. Because sorbitol and galactitol cannot easily diffuse out of cells, their intracellular concentration increases. Osmotic forces then cause water to diffuse into the cell, resulting in electrolyte imbalance. The resultant damage to lens epithelial cells, which have a high concentration of aldose reductase, is responsible for the cataract seen in children and in experimental animals with galactosemia and in animals with experimental diabetes mellitus.[12] Because aldose reductase is also found in high concentration in retinal pericytes and Schwann cells, some investigators suggest that diabetic retinopathy and neuropathy may be caused by aldose reductase-mediated damage. Despite all of these theoretical benefits, clinical trials have thus far failed to show a reduction in the incidence of diabetic retinopathy or of neuropathy by aldose reductase inhibitors, possibly because an effective aldose reductase inhibitor with few systemic side effects has yet to be developed.[12] Vasoproliferative Factors Currently intense interest exists in vasoproliferative factors released by the retina itself, retinal vessels, and the retinal pigment epithelium, which are felt to induce neovascularization. Vascular endothelial growth factor (VEGF), which inhibits the growth of the retinal endothelial cells in vitro, has been implicated in diabetic retinopathy. Considerable evidence suggests that VEGF has a direct role in the proliferative retinal vascular abnormalities that are found in diabetes. Animal models have demonstrated that VEGF expression correlates with the development and regression of neovascularization. [13] The concentration of VEGF in aqueous and vitreous directly correlates with the severity of retinopathy.[14] Angiogenesis is a complex process; many other growth factors and cytokines have been implicated in the development of diabetic retinopathy. Platelets and Blood Viscosity Diabetes is associated with abnormalities of platelet function. It has been postulated that platelet abnormalities or alterations in blood viscosity in diabetics may contribute to diabetic retinopathy by causing focal capillary occlusion and focal areas of ischemia in the retina which, in turn, contribute to the development of diabetic retinopathy