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| 年龄相关性黄斑变性患者的Toll样受体3和地图样萎缩 |
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| Toll-like receptor 3 and geographic atrophy in age-related macular degeneration |
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| Yang Z., Stratton C., Francis P.J., Kleinman M.E., Tan P.L., Gibbs D., Tong Z., Chen H., Constantine R., Yang X., Chen Y., Zeng J., Davey L., Ma X., Hau V.S., Wang C., Harmon J., Buehler J., Pearson E., Patel S., Kaminoh Y., Watkins S., Luo L., Zabriskie 2009/5/29 18:39:20 |
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New England Journal of Medicine, 2008, Volume 359, Issue 14
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| BACKGROUND: Age-related macular degeneration is the most common cause of irreversible visual impairment in the developed world. Advanced age-related macular degeneration consists of geographic atrophy and choroidal neovascularization. The specific genetic variants that predispose patients to geographic atrophy are largely unknown. METHODS: We tested for an association between the functional toll-like receptor 3 gene (TLR3) variant rs3775291 (involving the substitution of phenylalanine for leucine at amino acid 412) and age-related macular degeneration in Americans of European descent. We also tested for the effect of TLR3 Leu and Phe variants on the viability of human retinal pigment epithelial cells in vitro and on apoptosis of retinal pigment epithelial cells from wild-type mice and Tlr3-knockout (Tlr3-/-) mice. RESULTS: The Phe variant (encoded by the T allele at rs3775291) was associated with protection against geographic atrophy (P = 0.005). This association was replicated in two independent case-control series of geographic atrophy (P = 5.43 × 10-4 and P = 0.002). No association was found between TLR3 variants and choroidal neovascularization. A prototypic TLR3 ligand induced apoptosis in a greater fraction of human retinal pigment epithelial cells with the Leu-Leu genotype than those with the Leu-Phe genotype and in a greater fraction of wild-type mice than Tlr3-/- mice. CONCLUSIONS: The TLR3 412Phe variant confers protection against geographic atrophy, probably by suppressing the death of retinal pigment epithelial cells. Since double-stranded RNA (dsRNA) can activate TLR3-mediated apoptosis, our results suggest a role of viral dsRNA in the development of geographic atrophy and point to the potential toxic effects of short-interfering-RNA therapies in the eye. Copyright © 2008 Massachusetts Medical Society. |
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| Correspondence Address: Katsanis, N.; Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD 21205, United States; email: nkatsan1@jhmi.edu |
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 疾病资源中心
王燕燕 王曙
上海交通大学附属瑞金医院内分泌科
患者，女，69岁。2009年1月无明显诱因下出现乏力，当时程度较轻，未予以重视。2009年3月患者乏力症状加重，尿色逐渐加深，大便习惯改变，颜色变淡。4月18日入我院感染科治疗，诉轻度头晕、心慌，体重减轻10kg。无肝区疼痛，无发热，无腹痛、腹泻、腹胀、里急后重，无恶性、呕吐等。入院半月前于外院就诊，查肝功能：ALT 601IU/L，AST 785IU/L，TBIL 97.7umol/L，白蛋白 41g/L，甲状腺功能：游离T3 30.6pmol/L，游离T4 51.9pmol/L，心电图示快速房颤。
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