Oxidative Stress and Vascular Dysfunction in the Retina: Therapeutic Strategies

Abstract

Many retinal diseases, such as diabetic retinopathy, glaucoma, and age-related macular (AMD) degeneration, are associated with elevated reactive oxygen species (ROS) levels. ROS are important intracellular signaling molecules that regulate numerous physiological actions, including vascular reactivity and neuron function. However, excessive ROS formation has been linked to vascular endothelial dysfunction, neuron degeneration, and inflammation in the retina. ROS can directly modify cellular molecules and impair their function. Moreover, ROS can stimulate the production of inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) causing inflammation and cell death. However, there are various compounds with direct or indirect antioxidant activity that have been used to reduce ROS accumulation in animal models and humans. In this review, we report on the physiological and pathophysiological role of ROS in the retina with a special focus on the vascular system. Moreover, we present therapeutic approaches for individual retinal diseases targeting retinal signaling pathways involving ROS.

Keywords: oxidative stress; reactive oxygen species; retinal disease; vascular endothelium.

Figure 1

Yearly number of publications containing the search term “oxidative stress AND retina” from 2004–2019 [12].

Figure 2

Oxidative stress in the retina (ROS: reactive oxygen species; ¹△g: singlet oxygen; O₂^•−: superoxide; HO₂^•: hydroperoxyl; H₂O₂: hydrogen peroxide; ^•OH: hydroxyl; NADPH oxidase: nicotinamide adenine dinucleotide phosphate oxidase; eNOS: endothelial nitric oxide synthase; SOD: superoxide dismutase; RGC: retinal ganglion cell; RPE: retinal pigment epithelium; DR: diabetic retinopathy; AMD: age-related macular degeneration).

Figure 3

Pathophysiological mechanisms of ROS in diabetic retinopathy (MAPK: mitogen-activated protein kinase; RAS: renin-angiotensin system; PKC: protein kinase C; AGE: advanced glycation endproduct; ROS: reactive oxygen species; NADPH oxidase: nicotinamide adenine dinucleotide phosphate oxidase; eNOS: endothelial nitric oxide synthase; RGC: retinal ganglion cell).