Oxidative stress and diabetic retinopathy: Molecular mechanisms, pathogenetic role and therapeutic implications

Abstract

Oxidative stress, a cytopathic outcome of excessive generation of ROS and the repression of antioxidant defense system for ROS elimination, is involved in the pathogenesis of multiple diseases, including diabetes and its complications. Retinopathy, a microvascular complication of diabetes, is the primary cause of acquired blindness in diabetic patients. Oxidative stress has been verified as one critical contributor to the pathogenesis of diabetic retinopathy. Oxidative stress can both contribute to and result from the metabolic abnormalities induced by hyperglycemia, mainly including the increased flux of the polyol pathway and hexosamine pathway, the hyper-activation of protein kinase C (PKC) isoforms, and the accumulation of advanced glycation end products (AGEs). Moreover, the repression of the antioxidant defense system by hyperglycemia-mediated epigenetic modification also leads to the imbalance between the scavenging and production of ROS. Excessive accumulation of ROS induces mitochondrial damage, cellular apoptosis, inflammation, lipid peroxidation, and structural and functional alterations in retina. Therefore, it is important to understand and elucidate the oxidative stress-related mechanisms underlying the progress of diabetic retinopathy. In addition, the abnormalities correlated with oxidative stress provide multiple potential therapeutic targets to develop safe and effective treatments for diabetic retinopathy. Here, we also summarized the main antioxidant therapeutic strategies to control this disease.

Graphical abstract

Highlights

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  Oxidative stress can both contribute to and result from hyperglycemia-induced metabolic abnormalities in retina.

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  Genes important in regulation of ROS are epigenetically modified, increasing ROS accumulation in retina.

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  Oxidative stress is closely associated with the pathological changes in the progress of diabetic retinopathy.

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  Antioxidants ameliorate retinopathy through targeting multiple steps of oxidative stress.