Department of Ophthalmology, Kaohsiung Veterans General Hospital, Kaohsiung City, Taiwan.
J Ocul Pharmacol Ther. 2010 Jun;26(3):231-6. doi: 10.1089/jop.2009.0137.
Although the exact pathogenesis of age-related macular degeneration (AMD) is not clear, most studies indicate a role for retinal pigment epithelial (RPE) cell damage and death caused by oxidative stress. The purpose of this study was to examine the potential protective effects of lutein, zeaxanthin, meclofenamic acid, and resveratrol on the acrolein-induced oxidative stress in human RPE cells.
Cultured human RPE R-50 cells were treated with acrolein at different concentrations and treatment times. The protective effects of lutein (100 microM), zeaxanthin (100 microM), meclofenamic acid (30 microM), and resveratrol (10 microM) were investigated by pretreatment with the above agents before toxicant exposure in acute toxicity models and cotreatment with the toxicant in chronic toxicity models. The synergistic effects of acrolein and hydrogen peroxide exposure were also studied. Fluorescent latex beads were used to assess the phagocytic function of the cells.
Acrolein inhibited the phagocytic function of human RPE R-50 cells, and the inhibitory effects were time dependent. Pretreatment with lutein, zeaxanthin, meclofenamic acid, or resveratrol alleviated the inhibition of phagocytosis in the acute acrolein and combined acrolein/hydrogen peroxide toxicity models. Synergistic effects were seen between zeaxanthin and resveratrol or meclofenamic acid. Cotreatment with lutein, zeaxanthin, meclofenamic acid, or resveratrol showed a protective effect against the damage caused by 7-day acrolein exposure followed by hydrogen peroxide treatment.
Our results indicated an inhibitory effect of compounds found in cigarette smoke on human RPE phagocytosis, and lutein, zeaxanthin, meclofenamic acid, and resveratrol each offered protection against this inhibition. Therefore, red wine polyphenol, resveratrol, might ameliorate acrolein-induced or age-related RPE degeneration, such as AMD.
虽然年龄相关性黄斑变性（AMD）的确切发病机制尚不清楚，但大多数研究表明，视网膜色素上皮（RPE）细胞的氧化应激损伤和死亡起重要作用。本研究旨在探讨叶黄素、玉米黄质、甲氯芬那酸和白藜芦醇对人 RPE 细胞丙烯醛诱导的氧化应激的潜在保护作用。
在不同浓度和处理时间下用丙烯醛处理培养的人 RPE R-50 细胞。在急性毒性模型中，通过毒物暴露前用上述药物预处理来研究叶黄素（100μM）、玉米黄质（100μM）、甲氯芬那酸（30μM）和白藜芦醇（10μM）的保护作用，在慢性毒性模型中用毒物与药物共同处理来研究。还研究了丙烯醛和过氧化氢暴露的协同作用。荧光乳胶珠用于评估细胞的吞噬功能。
丙烯醛抑制人 RPE R-50 细胞的吞噬功能，且抑制作用具有时间依赖性。叶黄素、玉米黄质、甲氯芬那酸或白藜芦醇预处理可减轻急性丙烯醛和丙烯醛/过氧化氢联合毒性模型中吞噬作用的抑制。玉米黄质和白藜芦醇或甲氯芬那酸之间存在协同作用。叶黄素、玉米黄质、甲氯芬那酸或白藜芦醇共同处理对 7 天丙烯醛暴露后过氧化氢处理引起的损伤具有保护作用。
我们的结果表明，香烟烟雾中化合物对人 RPE 吞噬作用具有抑制作用，叶黄素、玉米黄质、甲氯芬那酸和白藜芦醇均可对此抑制作用提供保护。因此，红酒多酚白藜芦醇可能会改善丙烯醛诱导或年龄相关性 RPE 变性，如 AMD。
