Ccl2/Cx3cr1-deficient mice:: An animal model for age-related macular degeneration
Ccl2/Cx3cr1-deficient mice:: An animal model for age-related macular degeneration
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DOI：
10.1159/000119862
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发表时间：
2008-01-01
影响因子：
2.1
通讯作者：
Tuo, Jingsheng
中科院分区：
文献类型：
--
作者：
Chan, Chi-Chao;Ross, Robert J.;Tuo, Jingsheng
背景/目的：衰老的CCL2(-/-)小鼠表现为人类老年性黄斑变性(AMD)的基本特征。CX3CR1功能缺失单核苷酸多态与AMD相关。方法：建立CCL2(-/-)/CX3CR1(-/-)[双基因敲除(DKO)]小鼠，采用眼底镜常规组织学、免疫化学、生化和蛋白质组学方法进行评价。结果：6周龄时，所有DKO小鼠均出现视网膜色素上皮细胞异常、玻璃体形成、光感受器萎缩、脉络膜新生血管等AMD样视网膜病变，且随年龄增长而加重，高omega-3长链多不饱和脂肪酸饮食可逆转AMD样视网膜病变。在DKO视网膜色素上皮细胞中，主要的脂褐素荧光团N-视黄醛-N-视黄乙醇胺(A2E)在600 nm附近的发射峰明显升高。DKO组小鼠视网膜ERp29表达降低。结论：AMD小鼠发病早、外显性强，可能与某些趋化因子、A2E和内质网蛋白有关。版权所有(C)2008 S.Karger AG，巴塞尔。
Background/Aims: Senescent Ccl2(-/-) mice develop cardinal features of human age-related macular degeneration (AMD). Loss-of-function single-nucleotide polymorphisms within CX3CR1 are associated with AMD. Methods: We generated Ccl2(-/-)/Cx3cr1(-/-) [double-knockout (DKO)] mice and evaluated the eyes using fundoscopy routine histology, immunochemistry, biochemistry and proteomics. Results: At 6 weeks old, all DKO mice developed AMD-like retinal lesions such as abnormal retinal pigment epithelium cells, drusen, photoreceptor atrophy and choroidal neovascularization, which progressed with age and reversed with high omega-3 long-chain polyunsaturated fatty acid diet. N-retinylidene-N-retinylethanolamine (A2E), a major lipofuscin fluorophore, illustrated by an emission peak at similar to 600 nm, was significantly higher in DKO retinal pigment epithelium. Decreased ERp29 was found in the retina of DKO mice. Conclusion: A broad spectrum of AMD pathologies with early onset and high penetrance in these mice implicate certain chemokines, A2E and endoplasmic reticulum proteins in AMD pathogenesis. Copyright (c) 2008 S. Karger AG, Basel.