AGE and RAGE inhibitors in the treatment of diabetic retinopathy

Diabetic retinopathy is a major complication of diabetes and several biochemical/molecular mechanisms have been proposed as key instigators in the initiation and progression of the condition. Accumulating evidence suggests that formation of advanced glycation end products (AGEs) within the diabetic milieu is one of the contributing factors to neural and microvascular abnormalities as retinopathy progresses. This review highlights the pathogenesis of diabetic retinopathy, with special emphasis on AGEs, their receptors and the potential role of AGE-inhibiting agents. Retinopathy may be associated with an upregulation of the receptor for AGEs (RAGE) in a proinflammatory axis, concomitant with increases in AGEs. Therefore, this review will also detail the role of RAGE in AGE trafficking, its various ligands and the possibilities for targeting RAGE for therapeutic exploitation to prevent retinopathy in patients with diabetes.