氧化磷脂在年龄相关性黄斑变性中的作用及机制

项目名称： 氧化磷脂在年龄相关性黄斑变性中的作用及机制

项目编号： No.81470654

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 杜红俊

作者单位： 中国人民解放军第四军医大学

项目金额： 73万元

中文摘要： 年龄相关性黄斑变性（AMD）的病因不清,治疗难令人满意。年龄、光照等原因可引起视网膜色素上皮(RPE)细胞吞噬感光细胞外节能力下降，进而脂质代谢物沉积形成玻璃膜疣。玻璃膜疣中富含的多不饱和脂肪酸磷脂在黄斑部高氧化应激条件下形成氧化磷脂（oxPLs）。OxPLs已被证明在动脉粥样硬化病变中具有核心作用。AMD和动脉粥样硬化同为年龄相关性疾病，玻璃膜疣和粥样硬化斑块结构类似。因此我们推测oxPLs在AMD的发病中可能具有同样重要作用。我们前期采用氧化低密度脂蛋白作为oxPLS的载体，证实oxPLS视网膜下注射可诱导小鼠CNV样病变，但详细机理不清。本项目拟在此基础上，采用细胞培养、转基因动物和免疫化学染色等方法，深入研究oxPLs影响RPE细胞生物功能和诱导AMD样改变的详细机理。同时观察老龄和改变脂类代谢对这一过程的影响。研究结果将有助于阐明AMD的发病机理和寻找新的治疗靶点。

中文关键词： 脉络膜新生血管；年龄相关性黄斑变性；氧化磷脂；视网膜色素上皮；氧化应激

英文摘要： The pathogenesis of age-related macular degeneration (AMD) is not very clear and treatments towards AMD are still not satisfied nowadays. Age,sun exposure and other factors can impact the phagocytotic ability of retinal pigment epithelial (RPE) cells for photoreceptors outer segments, leading to the deposition of lipid and drusen formation. Drusen is highly enriched with polyunsaturated fatty acid phospholipids, which can be modified to oxidized phospholipids (oxLPs) under the high oxidative condition around macular. OxPLs have been extensively studied and proved to have a key role in atherosclerotic lesion development. Due to the similarities between AMD and atherosclerosis in relation with aging and similar structures between drusen and atherosclerotic plaque, we speculate that oxLPs may also play an important role in the pathogenesis of AMD. Our former experiments shown that oxPLs on oxidized low density lipoprotein (oxLDL) could induce CNV-like lesion in mouse when injected subretinally. In this project, by using cell culture, transgenic animals and immunostaining methods, we will conduct further research on influences of oxPLs on RPE cells and CNV-like lesion formation in mice, and how these effects were exerted. At the same time, we will observe effects of aging and lipid metabolism in this process. The finding of this research may have significance in clarifying the pathogenesis of AMD and in seeking new therapeutic targets for AMD

英文关键词： choroidal neovascularization;age related macular degeneration;oxidized phospholipids;retinal pigment epithelium;oxidative stress