Department of Life and Nanopharmaceutical Science of Pharmacy, College of Pharmacy, Kyung Hee University, Seoul, Republic of Korea.
Department of Preventive Pharmacy and Toxicology, College of Pharmacy, Kyung Hee University, 26, Kyungheedae-ro, Dongdaemun-gu, Seoul, 02447, Republic of Korea.
Arch Pharm Res. 2016 Dec;39(12):1703-1715. doi: 10.1007/s12272-016-0839-0. Epub 2016 Sep 22.
Damage of retinal pigment epithelial (RPE) cells by A2E may be critical for age-related macular degeneration (AMD) management. Accumulation and photooxidation of A2E are known to be one of the critical causes in AMD. Here, we evaluated the protective effect of resveratrol (RES), piceatannol (PIC) and RES glycones on blue-light-induced RPE cell death caused by A2E photooxidation. A2E treatment followed by blue light exposure caused significant damages on human RPE cells (ARPE-19). But the damages were attenuated by post- and pre-treatment of RES and PIC in our in vitro models. The results of cell free system and FAB-MS analysis clearly showed that the reduction of A2E by blue light exposure was significantly rescued, and that oxidized forms of A2E were significantly reduced by RES or PIC treatment. Besides, RES or PIC inhibited the intracellular accumulation of A2E. Not only RES and PIC but RES glycones showed protection of ARPE-19 cells against A2E and blue-light-induced photo-damage. These findings demonstrate that RES and its analogs may have protective effects against A2E and blue-light-induced ARPE-19 cell death through regulation of A2E accumulation as well as photooxidation of A2E. Thus RES and its analogs may be beneficial for AMD treatment.
视网膜色素上皮 (RPE) 细胞的损伤可能是年龄相关性黄斑变性 (AMD) 管理的关键。已知 A2E 的积累和光氧化是 AMD 的关键原因之一。在这里，我们评估了白藜芦醇 (RES)、白皮杉醇 (PIC) 和 RES 糖苷对 A2E 光氧化诱导的蓝光诱导的 RPE 细胞死亡的保护作用。A2E 处理后再进行蓝光照射会对人 RPE 细胞 (ARPE-19) 造成严重损伤。但在我们的体外模型中，RES 和 PIC 的后处理和预处理可减轻损伤。无细胞体系和 FAB-MS 分析的结果清楚地表明，蓝光暴露对 A2E 的还原明显得到挽救，而 RES 或 PIC 处理可显著减少 A2E 的氧化形式。此外，RES 或 PIC 可抑制细胞内 A2E 的积累。不仅 RES 和 PIC，RES 糖苷对 ARPE-19 细胞也具有保护作用，可防止 A2E 和蓝光诱导的光损伤。这些发现表明，RES 及其类似物可能通过调节 A2E 的积累以及 A2E 的光氧化对 A2E 和蓝光诱导的 ARPE-19 细胞死亡具有保护作用。因此，RES 及其类似物可能有益于 AMD 的治疗。
