Molecular mechanisms of diabetic retinopathy: potential therapeutic targets

Abstract

Diabetic retinopathy (DR) is the leading cause of blindness in working-age adults in United States. Research indicates an association between oxidative stress and the development of diabetes complications. However, clinical trials with general antioxidants have failed to prove effective in diabetic patients. Mounting evidence from experimental studies that continue to elucidate the damaging effects of oxidative stress and inflammation in both vascular and neural retina suggest its critical role in the pathogenesis of DR. This review will outline the current management of DR as well as present potential experimental therapeutic interventions, focusing on molecules that link oxidative stress to inflammation to provide potential therapeutic targets for treatment or prevention of DR. Understanding the biochemical changes and the molecular events under diabetic conditions could provide new effective therapeutic tools to combat the disease.

Keywords: Diabetic Retinopathy; Endoplasmic Reticulum-stress; Inflammation; Nicotinamide Adenine Dinucleotide Phosphate Oxidase; Oxidative Stress; Peroxynitrite; Therapeutics.

Figure 1

Schematic representation of the possible molecular pathways by which diabetes/high glucose induce generation of superoxide anion including nicotinamide adenine dinucleotide phosphate oxidase, mitochondrial oxidase, receptor for advanced glycation end products, protein kinase C, polylol, hexosamine pathway. Nitric oxide is generated by nitric oxide synthase to form the oxidant peroxynitrite and inhibit the thioredoxin (Trx) antioxidant defense resulting in increases in Trx interacting protein (TXNIP). Increases in TXNIP and endoplasmic reticulum-stress have been linked to activation of proinflammatory cytokine production and development of diabetic retinopathy