Advanced glycation end products (AGEs), oxidative stress and diabetic retinopathy

Diabetic retinopathy is a common and devastating microvascular complication in diabetes and is a leading cause of acquired blindness among the people of occupational age. Recent large landmark clinical studies have shown that intensive control of blood glucose or blood pressure (BP) reduces the risk for diabetic retinopathy. However, the strict control of blood glucose or BP is often difficult to maintain. Further, current therapeutic options for the treatment of sight-threatening proliferative diabetic retinopathy (PDR) such as photocoagulation and vitrectomy are limited by considerable side effects and far from satisfactory. Therefore, to develop novel therapeutic strategies that specifically target PDR is actually desired for most patients with diabetes. Although various biochemical and hemodynamic pathways are implicated in the diabetic retinopathy, recent clinical study has substantiated the concept of 'metabolic memory', and suggested the active involvement of advanced glycation end products (AGEs) and oxidative stress in this sight-threatening disorder. We, along with others, have recently found that pigment epithelium-derived factor (PEDF), a glycoprotein with complex neuroprotective, anti-angiogenic, anti-oxidative, and anti-inflammatory properties, could potentially be exploited as a therapeutic option for the treatment of diabetic retinopathy. Therefore, this article summarizes the role of AGEs and oxidative stress in diabetic retinopathy and discusses a potential utility of the blockade of this system by PEDF in this devastating disorder.