Suppression of Light-Induced Oxidative Stress in the Retina by Mitochondria-Targeted Antioxidant
Suppression of Light-Induced Oxidative Stress in the Retina by Mitochondria-Targeted Antioxidant
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DOI：
10.3390/antiox8010003
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发表时间：
2019-01-01
期刊：
影响因子：
7
通讯作者：
Zernii, Evgeni Yu.
中科院分区：
文献类型：
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作者：
Baksheeva, Viktoriia E.;Tiulina, Veronika V.;Zernii, Evgeni Yu.
光诱导的脂质和蛋白质的氧化会引起视网膜损伤，并导致视网膜退行性疾病的进展，例如医源性光性黄斑病变。经过多年的积累，视网膜损伤导致了老年性黄斑变性(AMD)的发展。抗氧化剂治疗被认为是保护视网膜免受光损伤和AMD的一种有前途的方法。在这里，我们使用线粒体靶向抗氧化剂skq1(10-(6‘-plastoquinonyl)decyltriphenyl-phosphonium).检测了在有或没有预先用药的情况下，过度光照诱导的兔视网膜的氧化过程。用比色法和发光法对染毒后1~7d内处死动物的视网膜提取液中的过氧化氢、丙二醛(MDA)、总抗氧化活性(AOA)、谷胱甘肽过氧化物酶(GPx)和超氧化物歧化酶(SOD)活性进行了分析。免疫印迹法检测视黄素的氧化情况。光照诱导视网膜细胞脂质过氧化和H_2O_2积聚。出乎意料的是，它显著上调了视网膜提取液中的AOA，尽管SOD和GPX的活性受到了影响。伴随着这些变化的是Arrestin的二硫键二聚体的积累，揭示了光感受器中的氧化应激。用SkQ1预先给眼睛用药可以加速过氧化氢水平的正常化以及脂质和蛋白质的氧化还原状态，同时提高AOA，并可能维持GPX的正常活动。因此，SkQ1保护视网膜免受光诱导的氧化应激，并可用于抑制导致AMD的蛋白质和脂质的氧化损伤。
Light-induced oxidation of lipids and proteins provokes retinal injuries and results in progression of degenerative retinal diseases, such as, for instance, iatrogenic photic maculopathies. Having accumulated over years retinal injuries contribute to development of age-related macular degeneration (AMD). Antioxidant treatment is regarded as a promising approach to protecting the retina from light damage and AMD. Here, we examine oxidative processes induced in rabbit retina by excessive light illumination with or without premedication using mitochondria-targeted antioxidant SkQ1 (10-(6'-plastoquinonyl)decyltriphenyl-phosphonium). The retinal extracts obtained from animals euthanized within 1-7 days post exposure were analyzed for H2O2, malondialdehyde (MDA), total antioxidant activity (AOA), and activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD) using colorimetric and luminescence assays. Oxidation of visual arrestin was monitored by immunoblotting. The light exposure induced lipid peroxidation and H2O2 accumulation in the retinal cells. Unexpectedly, it prominently upregulated AOA in retinal extracts although SOD and GPx activities were compromised. These alterations were accompanied by accumulation of disulfide dimers of arrestin revealing oxidative stress in the photoreceptors. Premedication of the eyes with SkQ1 accelerated normalization of H2O2 levels and redox-status of lipids and proteins, contemporarily enhancing AOA and, likely, sustaining normal activity of GPx. Thus, SkQ1 protects the retina from light-induced oxidative stress and could be employed to suppress oxidative damage of proteins and lipids contributing to AMD.