Improved Effect of a Mitochondria-Targeted Antioxidant on Hydrogen Peroxide-Induced Oxidative Stress in Human Retinal Pigment Epithelium Cells

Abstract

Background: Oxidative damage to retinal pigment epithelial (RPE) cells contributes to the development of age-related macular degeneration, which is among the leading causes of visual loss in elderly people. In the present study, we evaluated the protective role of triphenylphosphonium (TPP)-Niacin against hydrogen peroxide (H2O2)-induced oxidative stress in RPE cells.Methods: The cellular viability, lactate dehydrogenase release, reactive oxygen species (ROS) generation, and mitochondrial function of retinal ARPE-19 cells were determined under treatment with H2O2 or pre-treatment with TPP-Niacin. The expression level of mitochondrial related genes and some transcription factors were assessed using real-time polymerase chain reaction (RT-qPCR). Results: TPP-Niacin significantly improved cell viability, reduced ROS generation, and increased the antioxidant enzymes in H2O2-treated ARPE-19 cells. Mitochondrial dysfunction from the H2O2-induced oxidative stress was also considerably diminished by TPP-Niacin treatment, along with reduction of the mitochondrial membrane potential (MMP) and upregulation of the mitochondrial-associated gene. In addition, TPP-Niacin markedly enhanced the expression of transcription factors (PGC-1α and NRF2) and antioxidant-associated genes (especially HO-1 and NQO-1).Conclusion: We verified the protective effect of TPP-Niacin against H2O2-induced oxidative stress in RPE cells. TPP-Niacin is believed to protect against mitochondrial dysfunction by upregulating antioxidant-related genes, such as PGC-1α, NRF2, HO-1, and NQO-1, in RPE cells.

LXA4 protects against blue-light induced retinal degeneration in human A2E-laden RPE cells and Balb-c mice

“…Under resting conditions, NRF2 and Kelch-like ECH-associated protein 1 (Keap1) in the RPE cytoplasm bind to each other, and the antioxidant genes are not stimulated (10). When ROS production increases, NRF2 separates from the Keap1 protein, enters the nucleus and activates the expression of HO1, NQO1 and other antioxidant enzymes, thus playing an antioxidant role (11). The materials constitute a pleiotropic cellular defense, which eliminates ROS and xenobiotics, detoxifies electrophiles, and maintains the intracellular reducing potential to attenuate BL-induced inflammation and oxidative damage, all of which could represent promising strategies for the prevention of AMD (12).…”