Abstract
Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly, and oxidative damage to retinal pigment epithelial (RPE) cells plays a major role in the pathogenesis of AMD. Exposure to high levels of atmospheric particulate matter (PM) with an aerodynamic diameter of <2.5 μm (PM2.5) causes respiratory injury, primarily due to oxidative stress. Recently, a large community-based cohort study in the UK reported a positive correlation between PM2.5 exposure and AMD. Sulforaphane (SFN), a natural isothiocyanate found in cruciferous vegetables, has known antioxidant effects. However, the protective effects of SNF in the eye, especially in the context of AMD, have not been evaluated. In the present study, we evaluated the effect of SFN against PM2.5-induced toxicity in human RPE cells (ARPE-19) and elucidated the molecular mechanism of action. Exposure to PM2.5 decreased cell viability in ARPE-19 cells in a time- and dose-dependent manner, potentially due to elevated intracellular reactive oxygen species (ROS). SFN treatment increased ARPE-19 cell viability and decreased PM2.5-induced oxidative stress in a dose-dependent manner. PM2.5-induced downregulation of serum- and glucocorticoid-inducible kinase 1 (SGK1), a cell survival factor, was recovered by SFN. PM2.5 treatment decreased the enzymatic activities of the antioxidant enzymes including superoxide dismutase and catalase, which were restored by SFN treatment. Taken together, these findings suggest that SFN effectively alleviates PM2.5-induced oxidative damage in human ARPE-19 cells via its antioxidant effects, and that SFN can potentially be used as a therapeutic agent for AMD, particularly in cases related to PM2.5 exposure.
Highlights
Age-related macular degeneration (AMD) is the most devastating chorioretinal disease, and is a leading cause of blindness in the elderly population [1]
We aimed to investigate whether SFN could alleviate PM2.5induced oxidative stress in human retinal pigment epithelial cells (ARPE-19), and subsequently to explore the mechanisms underlying the antioxidant effects of SFN in this context
These results indicated that the amount of lactate dehydrogenase (LDH) released from cells treated with PM2.5 was related to cell viability, and that SFN alleviated PM2.5induced cytotoxicity
Summary
Age-related macular degeneration (AMD) is the most devastating chorioretinal disease, and is a leading cause of blindness in the elderly population [1]. The retinal pigment epithelium (RPE) is a monolayer of cells located between the retinal photoreceptors and choroid vascular bed. RPE cells support photoreceptors, which are both postmitotic and highly sensitive to environmental insults, and subject to irreversible degeneration. RPE cells are continuously exposed to reactive oxygen species (ROS) due to light exposure, high retinal oxygen consumption, and abundant polyunsaturated fatty acids and photosensitizers in photoreceptors and the RPE [2]. Chronic excessive ROS production and accumulation cause oxidative dysfunction in the RPE, which leads to photoreceptor loss in the advanced form of AMD, geographic atrophy [3]. PM2.5 accumulation causes oxidative stress in the body [7], which is considered to be an important molecular mechanism of PM2.5-mediated toxicity [8]
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