Mice with cholesterol in Bruch's membrane: have we arrived?
Mice with cholesterol in Bruch's membrane: have we arrived?
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布鲁赫膜中含有胆固醇的小鼠：我们到了吗？
DOI：
10.1167/iovs.14-15858
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发表时间：
2014
影响因子：
4.4
通讯作者：
Curcio,ChristineA
中科院分区：
文献类型：
--
作者：
Curcio,ChristineA
最早发现的晶簇主要成分是脂类。此外，年龄相关性黄斑变性（AMD）的最大风险因素衰老的特征在于人类布鲁赫膜（Bruch’s membrane，BrM）的显著变性。这两种现象都归因于含有载脂蛋白B和E的富含酯化胆固醇（EC）的脂蛋白颗粒。这些在视网膜外细胞和脉络膜毛细血管之间形成疏水屏障，并汇集在AMD黄斑中形成软玻璃疣和基底线状存款。基因表达和分泌的研究暗示视网膜色素上皮细胞作为脂蛋白分泌。根据流行病学和遗传学的证据，这些发现提示了AMD病变生物发生的动脉粥样硬化激发的反应保留理论。1 Fujihara、Cano和Handa 2通过分析内源性apoB48系统缺陷小鼠脉络膜视网膜细胞和组织的apoB100脂蛋白表达和沉积来验证这一假设。值得注意的是，这些研究人员使用特定的菲律宾组织化学，以证明EC，电子显微镜的组织后固定最佳的细胞外脂质，和代谢标记，以确认载脂蛋白的合成。虽然EC和固体电子致密颗粒定位于BrM，但细胞外沉积物的缺乏导致作者得出结论，仅分泌不足以产生玻璃疣，即使在老年动物中也需要其他因素。
The earliest discovered and majority druse component by volume is lipid. Further, aging, the largest risk factor for age-related macular degeneration (AMD), features a marked lipidization of human Bruch’s membrane (BrM). Both phenomena are attributed to esterified cholesterol (EC)-rich lipoprotein particles containing apolipoproteins B and E. These form a hydrophobic barrier between outer retinal cells and choriocapillaris and pool to form soft drusen and basal linear deposit in AMD macula. Gene expression and secretion studies implicate the retinal pigment epithelium as a lipoprotein secretor. With evidence from epidemiology and genetics, these findings prompted the atherosclerosis-inspired response-to-retention theory of AMD lesion biogenesis. 1Fujihara, Cano, and Handa2 tested this hypothesis by analyzing chorioretinal cellular and tissue expression and deposition of apoB100 lipoproteins in mice systemically deficient in endogenous apoB48. Notably, these investigators used specific filipin histochemistry to demonstrate EC, electron microscopy of tissues postfixed optimally for extracellular lipid, and metabolic labeling to confirm apolipoprotein synthesis. Although EC and solid electron-dense particles localized to BrM, the absence of extracellular deposits led the authors to conclude that secretion alone is insufficient to produce drusen and that other factors are required, even in older animals.