N-Acetylcysteine Amide, a Thiol Antioxidant, Protects TBHP-Induced Oxidative Stress in Primary Human Retinal Pigment Epithelial Cells
Age-related macular degeneration (AMD) is a leading cause of blindness in Americans at ago 60 and older. AMD is a degenerative condition that begins in Bruch’s membrane and progresses to the retinal pigment epithelium and, ultimately, the overlying photoreceptors. While oxidative stress is implicated in the pathogenesis of AMD, dietary antioxidants have been shown to delay progression of AMD in clinical studies. We hypothesized that N-acetylcysteine amide (NACA), a thiol antioxidant, would impede progression of retinal degeneration. tert-Butyl hydroperoxide (tBHP) is a model hydroperoxidant used to induce oxidative stress in cell cultures. The goal of this work was to evaluate the efficacy of NACA in preventing tBHP-induced acute oxidative stress in primary human retinal pigment epithelial cells (hRPEpiC). Our data indicated that tBHP induced ROS generation and resulted in reduced cell viability, depletion of intracellular glutathione (GSH) levels and compromise of glutathione reductase (GR) activity. Pretreatment with NACA significantly reduced ROS generation, restored the level of GSH and GR activity, and recovered transepithelical electrical resistance (TEER). However, pretreatment of NACA did not decrease the number of dying cells, defined as early and late apoptotic cells from flow cytometry.Our data suggests that pretreatment with NACA reduces sublethal but not the lethal effect in primary cultures of human retinal pigment epithelial cells. NACA is a potent antioxidant that could be further evaluated as a potential treatment for dry AMD.
H. Wang et al., "N-Acetylcysteine Amide, a Thiol Antioxidant, Protects TBHP-Induced Oxidative Stress in Primary Human Retinal Pigment Epithelial Cells," Free Radical Biology & Medicine, vol. 100, no. Supplement, Elsevier, Nov 2016.
The definitive version is available at https://doi.org/10.1016/j.freeradbiomed.2016.10.294
Joint 23rd Annual Meeting of the Society for Redox Biology and Medicine and 18th Biennial Meeting of the Society for Free Radical Research International (2016: Nov. 16-19, San Francisco, CA)
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01 Nov 2016