Resveratrol Prevents Light-Induced Retinal Degeneration via Suppressing Activator Protein-1 Activation
Resveratrol Prevents Light-Induced Retinal Degeneration via Suppressing Activator Protein-1 Activation
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DOI：
10.2353/ajpath.2010.100098
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发表时间：
2010-10-01
影响因子：
6
通讯作者：
Tsubota, Kazuo
中科院分区：
文献类型：
--
作者：
Kubota, Shunsuke;Kurihara, Toshihide;Tsubota, Kazuo
在人类疾病和啮齿动物模型中，视网膜的光损伤加速了视网膜变性。近年来，多酚类植物防御素白藜芦醇除了具有经典的抗氧化作用外，还具有多种生物活性。在本研究中，我们研究了白藜芦醇对光诱导的视网膜变性的作用及其潜在的分子机制。将具有光暴露（5000勒克斯白色光3小时）的BALB/c小鼠以50 mg/kg的剂量口服预处理5天。通过TdT介导的dUTP缺口末端标记、外核层形态测量和视网膜电图评估视网膜损伤。白藜芦醇给药小鼠与光暴露导致光诱导的病理参数，包括TdT介导的dUTP缺口末端标记阳性视网膜细胞，外核层变薄，视网膜电图的变化显着抑制。为了阐明潜在的分子机制，激活蛋白-1亚基c-fos的核转位的酶联免疫吸附试验进行了评估，和视网膜活性sirtuin 1的脱乙酰酶荧光测定。视网膜激活蛋白-1的激活，上调曝光后，显着减少白藜芦醇的应用。与此同时，视网膜sirtuin 1活性，减少在动物的光损伤，显着增强白藜芦醇治疗。我们的数据表明，白藜芦醇作为一种治疗剂，以防止视网膜变性相关的光损伤的潜在用途。(Am J Pathol 2010，177：1725-1731; DOI：10.2353/ajpath.
Light damage to the retina accelerates retinal degeneration in human diseases and rodent models. Recently, the polyphenolic phytoalexin resveratrol has been shown to exert various bioactivities in addition to its classical antioxidant property. In the present study, we investigated the effect of resveratrol on light-induced retinal degeneration together with its underlying molecular mechanisms. BALB/c mice with light exposure (5000-lux white light for 3 hours) were orally pretreated with resveratrol at a dose of 50 mg/kg for 5 days. Retinal damage was evaluated by TdT-mediated dUTP nick-end labeling, outer nuclear layer morphometry, and electroretinography. Administration of resveratrol to mice with light exposure led to a significant suppression of light-induced pathological parameters, including TdT-mediated dUTP nick-end labeling-positive retinal cells, outer nuclear layer thinning, and electroretinography changes. To clarify the underlying molecular mechanisms, the nuclear translocation of activator protein-1 subunit c-fos was evaluated by enzyme-linked immunosorbent assay, and the retinal activity of sirtuin 1 was measured by deacetylase fluorometric assay. Retinal activator protein-1 activation, up-regulated following light exposure, was significantly reduced by application of resveratrol. In parallel, retinal sirtuin 1 activity, reduced in animals with light damage, was significantly augmented by resveratrol treatment. Our data suggest the potential use of resveratrol as a therapeutic agent to prevent retinal degeneration related to light damage. (Am J Pathol 2010, 1 77:1725-1731; DOI: 10.2353/ajpath.2010.100098)