Potential Role of Endoplasmic Reticulum Stress in Pathogenesis of Diabetic Retinopathy

Abstract

Diabetes mellitus is a metabolic disease that leads to several complications which include retinopathy. Multiple biochemical abnormalities have been proposed to explain the development of retinopathy, including oxidative stress. Although the existence of oxidative stress has been established in the retina from long standing diabetic animals, pathogenesis and progression of retinopathy remain unclear. In order to gain insight into the pathogenesis of diabetic retinopathy, we analyzed the levels of different oxidative stress biomarkers in the retina at early stages during the progress of streptozotocin-induced diabetes. No significant changes in glutathione content, expression of NADPH-oxidase, levels of lipid peroxidation, nor production of free radicals were observed in the retina up to 45 days of diabetes induction. Likewise, a transient decrease in aconitase activity, parallel to an increase in the superoxide dismutase activity was observed at 20 days of hyperglycemia, suggesting a high capacity of retina to maintain its redox homeostasis, at least at early stages of diabetes. Nonetheless, we found an early and time-dependent increase in the levels of oxidized proteins, which was not affected by the administration of the antioxidant quercetin. Also, positive immunoreactivity to the reticulum stress protein CHOP was found in glial Müller cells of diabetic rat retinas. These findings suggest the occurrence of endoplasmic reticulum stress as a primary event in retina pathogenesis in diabetes.

Associations between Fatty Acid-Binding Protein 4–A Proinflammatory Adipokine and Insulin Resistance, Gestational and Type 2 Diabetes Mellitus

“…Moreover, FABP4 is an obligatory mediator coupling toxic lipids (i.e., saturated fatty acids) to endoplasmic reticulum stress in macrophages in vitro and in vivo [55]. Interestingly, endoplasmic reticulum stress represents an initial event in retina pathogenesis in diabetes [10,91].…”

Lutein and Zeaxanthin Isomers Protect against Light-Induced Retinopathy via Decreasing Oxidative and Endoplasmic Reticulum Stress in BALB/cJ Mice

“…In addition to the role of oxidative stress (OS) involved in the pathogenesis of photoreceptor degeneration, endoplasmic reticulum stress (ERS) also contributed to retinal degeneration in a variety of conditions such as age-related macular degeneration [ 9 , 10 ], retinitis pigmentosa (RP), diabetic retinopathy [ 11 , 12 ], and glaucoma [ 13 , 14 ]. Light exposure was also reported to induce ERS as well as abnormal ER membranes and endomembranes in 661W cells [ 15 ].…”

Water-soluble C60 fullerene ameliorates astroglial reactivity and TNFa production in retina of diabetic rats

“…Clarification of reactivity of astroglial cells as well as the role of critical molecular pathways in retinal dysfunction will make it possible to construct an effective therapeutic strategy for DR treatment. Diabetic complications closely relate to consequent critical disturbances as a result of the high glucose level: the switching of glucose utilization to the polyol pathway, formation of advanced glycation-end products (AGEs), neuroinflammation, oxidative stress and excitotoxicity (Asnaghi et al, 2003;Sanchez-Chavez et al, 2016;Amato et al, 2018). Taking into account that S100β is a valid astrocyte marker, the results observed in the presented study showing an increase of S100β content evidence the generation of astrogliosis in the retina of diabetic rats.…”