Astaxanthin Protects Retinal Photoreceptor Cells against High Glucose-Induced Oxidative Stress by Induction of Antioxidant Enzymes via the PI3K/Akt/Nrf2 Pathway

Abstract

Diabetic retinopathy (DR) is a major microvascular complication that can lead to severe visual impairment in patients with diabetes. The elevated oxidative stress and increased reactive oxygen species (ROS) production induced by hyperglycemia have been reported to play an important role in the complex pathogenesis of DR. Astaxanthin (AST), a natural carotenoid derivative, has been recently recognized as a strong free radical scavenger and might, therefore, be beneficial in different diseases, including DR. In this study, we evaluated the potential role of AST as an antioxidative and antiapoptotic agent in protecting retinal cells and also investigated the involvement of the PI3K/Akt/Nrf2 pathway in AST-mediated effects. We treated high glucose-cultured mouse photoreceptor cells (661W) with different concentrations of AST and analyzed ROS production and cell apoptosis in the different regimens. Moreover, we also analyzed the expression of PI3K, Akt, Nrf2, and Phase II enzymes after AST treatment. Our results showed that AST dose-dependently reduced ROS production and attenuated 661W cell apoptosis in a high glucose environment. Importantly, its protective effect was abolished by treatment with PI3K or Nrf2 inhibitors, indicating the involvement of the PI3K/Akt/Nrf2 pathway. These results suggest AST as a nutritional supplement that could benefit patients with DR.

Inhibitory Action of Antidiabetic Drugs on the Free Radical Production by the Rod Outer Segment Ectopic Aerobic Metabolism

“…In particular, rod OS appear vulnerable to oxidative stress [ 8 , 17 , 41 , 42 ], which drives the retinal degeneration [ 17 , 18 ]. On the other hand, antioxidants were shown to mitigate signs of DR in animal diabetic models [ 43 ] and in cultured photoreceptor cells (661W) [ 44 ].…”

Dihydromyricetin Alleviates High Glucose-Induced Oxidative Stress and Apoptosis in Human Retinal Pigment Epithelial Cells by Downregulating miR-34a Expression

“…Repeated cell exposure to oxidative stress leads to the insufficient activity of cellular antioxidant enzymes responding to ROS, contributing to the inability of RPE cells to prevent the consequent damages. 31 Excess intracellular ROS brings about the damage of macromolecules and acts as cellular messengers to activate a cascade of biochemical and molecular events and disrupt the normal mechanisms of cellular signaling, which leads to the disruption of normal retinal cellular physiology and apoptosis. 12 , 13 Therefore, anti-oxidation and anti-apoptosis may represent a promising therapy for the treatment of DR. DHM, also known as ampelopsin, is a dihydroflavonol flavonoid that is found in ampelopsis.…”

Herbal Formula Huangqi Guizhi Wuwu Decoction Attenuates Paclitaxel-related Neurotoxicity via Inhibition of Inflammation and Oxidative Stress

“…Modulation of Nrf2 may alleviate oxidative stress injury in PIPN (Singh et al, 2019) [29]. Notably, increasing evidence has suggested that PI3K/Akt is upstream of Nrf2 [30,31]. Nrf2-mediated gene expression correlates with the activation of the PI3K/Akt pathway.…”