Abstract

Ultraviolet radiation, especially UVA, can penetrate the lens, reach the retina, and induce oxidative stress to retinal pigment epithelial (RPE) cells. Even though it is weakly absorbed by protein and DNA, it may trigger the production of reactive oxygen species (ROS) and generate oxidative injury; oxidative injury to the retinal pigment epithelium has been implicated to play a contributory role in age-related macular degeneration (AMD). Studies showed that resveratrol, an abundant and active component of red grapes, can protect several cell types from oxidative stress. In this study, adult RPE cells being treated with different concentrations of resveratrol were used to evaluate the protective effect of resveratrol on RPE cells against UVA-induced damage. Cell viability assay showed that resveratrol reduced the UVA-induced decrease in RPE cell viability. Through flow cytometry analysis, we found that the generation of intracellular H2O2 induced by UVA irradiation in RPE cells could be suppressed by resveratrol in a concentration-dependent manner. Results of Western blot analysis demonstrated that resveratrol lowered the activation of UVA-induced extracellular signal-regulated kinase, c-jun-NH2 terminal kinase and p38 kinase in RPE cells. In addition, there was also a reduction in UVA-induced cyclooxygenase-2 (COX-2) expression in RPE cells pretreated with resveratrol. Our observations suggest that resveratrol is effective in preventing RPE cells from being damaged by UVA radiation, and is worth considering for further development as a chemoprotective agent for the prevention of early AMD.

Highlights

  • Oxidative injury and functional impairment of retinal pigment epithelial (RPE) cells may play an early and crucial role in the development of age-related macular degeneration (AMD) [1,2,3,4], one of the most common causes of severe visual loss in the elderly population in the developed world [5,6].Exposure to ultraviolet (UV) A and short-wavelength visible radiation, even from natural environment, may induce the production of reactive oxygen species (ROS) and result in oxidative damage to RPE cells [3,7,8]

  • The data indicate that resveratrol is safe for ARPE19 cells at the concentrations used in this study

  • Resveratrol belongs to the stilbene family of compounds, which are characterized by two aromatic rings joined by a methylene bridge

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Summary

Introduction

Oxidative injury and functional impairment of retinal pigment epithelial (RPE) cells may play an early and crucial role in the development of age-related macular degeneration (AMD) [1,2,3,4], one of the most common causes of severe visual loss in the elderly population in the developed world [5,6]. The retina of a child is susceptible to damage from UV exposure as the lens lacks the yellow pigment that prevents UV transmission [4]. Resveratrol has been reported to have antioxidant effects against hydrogen peroxide-induced oxidative stress [17] and acrolein-induced cytotoxicity in human RPE cells [18]. There have been few studies on the protective effects of resveratrol against UVA-induced damage, and the underlying mechanism of its effects is still unknown. We investigated the protective effects of resveratrol against UVA-induced decrease in RPE cell viability and the possible mechanisms involved, including the inhibition of UVA-induced intracellular hydrogen peroxide (H2O2) production, mitogen-activated protein kinase (MAPK) activation, and cyclooxygenase-2 (COX-2) expression

Resveratrol Has no Cytotoxicity on ARPE19 Cells
Resveratrol Reduced UVA-Induced Decrease in Cell Viability
Resveratrol Lessened UVA-Induced H2O2 Production
Resveratrol Suppressed UVA-Induced MAPK Activation
Resveratrol Lowered UVA-Induced COX-2 Expression
Discussion
Materials
Cell Preparation and UV Radiation
Cell Viability Assays
Flow Cytometric Analysis
Western Blot Analysis
Data Analysis

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