CX3CR1-dependent subretinal microglia cell accumulation is associated with cardinal features of age-related macular degeneration
CX3CR1-dependent subretinal microglia cell accumulation is associated with cardinal features of age-related macular degeneration
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DOI：
10.1172/jci31692
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发表时间：
2007-10-01
影响因子：
15.9
通讯作者：
Sennlaub, Florian
中科院分区：
文献类型：
--
作者：
Combadiere, Christophe;Feumi, Charles;Sennlaub, Florian
视网膜小胶质细胞（MC）在年龄相关性黄斑变性（AMD）中的作用尚不清楚。在这里，我们证明了所有的视网膜MCs表达CX3C趋化因子受体1（CX3CR1），并且与受损的细胞迁移相关的CX3CR1 M280等位基因的纯合性增加了AMD的风险。在患有AMD的人类中，MC在视网膜变性和脉络膜新生血管（CNV）的位点处的视网膜下腔中积累。在CX3CR1缺陷小鼠中，随着年龄的增长和白化病背景，以及激光照射后视网膜变性之前，MCs在视网膜下积累。在黑暗中饲养白化病小鼠可以避免这两种情况。衰老小鼠眼底镜下脂质肿胀的视网膜下MCs的外观是玻璃状的，并且CX3CR1依赖的MC积累与实验性CNV的加重相关。这些结果表明，CX3CR1依赖的视网膜下MCs的积累引起AMD的主要特征。这些发现揭示了我们认为是一种新的致病过程，对AMD新疗法的开发具有重要意义。
The role of retinal microglial cells (MCs) in age-related macular degeneration (AMD) is unclear. Here we demonstrated that all retinal MCs express CX3C chemokine receptor 1 (CX3CR1) and that homozygosity for the CX3CR1 M280 allele, which is associated with impaired cell migration, increases the risk of AMD. In humans with AMD, MCs accumulated in the subretinal space at sites of retinal degeneration and choroidal neovascularization (CNV). In CX3CR1-deficient mice, MCs accumulated subretinally with age and albino background and after laser impact preceding retinal degeneration. Raising the albino mice in the dark prevented both events. The appearance of lipid-bloated subretinal MCs was drusen-like on funduscopy of senescent mice, and CX3CR1-dependent MC accumulation was associated with an exacerbation of experimental CNV These results show that CX3CR1-dependent accumulation of subretinal MCs evokes cardinal features of AMD. These findings reveal what we believe to be a novel pathogenic process with important implications for the development of new therapies for AMD.