Paraquat-Induced Retinal Degeneration Is Exaggerated in CX3CR1-Deficient Mice and Is Associated with Increased Retinal Inflammation
Paraquat-Induced Retinal Degeneration Is Exaggerated in CX3CR1-Deficient Mice and Is Associated with Increased Retinal Inflammation
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DOI：
10.1167/iovs.12-10888
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发表时间：
2013-01-01
影响因子：
4.4
通讯作者：
Xu, Heping
中科院分区：
文献类型：
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作者：
Chen, Mei;Luo, Chang;Xu, Heping
目的.探讨Fractalkine受体CX 3CR 1通路在氧化性损伤介导的视网膜变性和免疫激活中的作用。将促氧化剂百草枯（0.75 μ M）注射到C57 BL/6 J、CX 3CR 1（gpf/+）和CX 3CR 1（gfp/gfp）小鼠的玻璃体中。视网膜病变的临床研究主题眼底内窥镜成像和荧光血管造影，并通过光镜和电镜病理。实时荧光定量PCR检测视网膜免疫基因表达。小胶质细胞活化和免疫细胞浸润通过视网膜平台的共聚焦显微镜检查。玻璃体内注射百草枯（0.75 μ M）导致急性视网膜毛细血管无灌注2天内，从4天到4周注射后（p.i.）改善。在感染后4天观察到全视网膜变性。并且在感染后4周进一步进展。在没有CX 3CR 1的情况下，视网膜变性被夸大，并伴有TNF-α、iNOS、IL-1 β、Ccl 2和Casp-1基因表达的增加。视网膜平片的共聚焦显微镜显示，在注射百草枯的眼睛中，小胶质细胞活化，CD 44（+）MHC-II+单核细胞和GR 1（+）中性粒细胞浸润。CX 3CR 1（gfp/gfp）小鼠中活化的小胶质细胞和浸润的白细胞数量显著高于CX 3CR 1（gfp/+）小鼠。我们的研究结果表明，CX 3CR 1信号通路可能在控制视网膜炎症氧化和缺血/再灌注条件下发挥重要作用。在不存在CX 3CR 1的情况下，不受控制的视网膜炎症导致夸张的视网膜变性。（Invest Ophthalmol维斯科学。2013; 54：682-690）DOI：10.1167/iovs.12-10888
PURPOSE. To investigate the role of the Fractalkine receptor CX3CR1 pathway in oxidative insults-mediated retinal degeneration and immune activation.METHODS. A prooxidant, paraquat (0.75 mu M) was injected into the vitreous of C57BL/6J, CX3CR1(gpf/+), and CX3CR1(gfp/gfp) mice. Retinal lesions were investigated clinically by topic endoscopic fundus imaging and fluorescence angiography, and pathologically by light-and electron microscopy. Retinal immune gene expression was determined by real-time RTPCR. Microglial activation and immune cell infiltration were examined by confocal microscopy of retinal flatmounts.RESULTS. Intravitreal injection of paraquat (0.75 mu M) resulted in acute retinal capillary nonperfusion within 2 days, which improved from 4 days to 4 weeks postinjection (p.i.). Panretinal degeneration was observed at 4 days p.i. and progressed further at 4 weeks p.i. In the absence of CX3CR1, retinal degeneration was exaggerated and was accompanied by increased TNF-alpha, iNOS, IL-1 beta, Ccl2, and Casp-1 gene expression. Confocal microscopy of retinal flatmounts revealed microglial activation and CD44(+)MHC-II+ monocyte and GR1(+) neutrophil infiltration in paraquat-injected eyes. The number of activated microglia and infiltrating leukocytes was significantly higher in CX3CR1(gfp/gfp) mice than in CX3CR1(gfp/+) mice.CONCLUSIONS. Our results suggest that the CX3CR1 signaling pathway may play an important role in controlling retinal inflammation under oxidative and ischemia/reperfusion conditions. In the absence of CX3CR1, uncontrolled retinal inflammation results in exaggerated retinal degeneration. (Invest Ophthalmol Vis Sci. 2013; 54: 682-690) DOI:10.1167/iovs.12-10888