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Mei Chen, Chang Luo, Rosana Penalva, Heping Xu; Paraquat-Induced Retinal Degeneration Is Exaggerated in CX3CR1-Deficient Mice and Is Associated with Increased Retinal Inflammation. Invest. Ophthalmol. Vis. Sci. 2013;54(1):682-690. doi: 10.1167/iovs.12-10888.
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To investigate the role of the Fractalkine receptor CX3CR1 pathway in oxidative insults–mediated retinal degeneration and immune activation.
A prooxidant, paraquat (0.75 μM) was injected into the vitreous of C57BL/6J, CX3CR1gpf/+, and CX3CR1gfp/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 RT-PCR. Microglial activation and immune cell infiltration were examined by confocal microscopy of retinal flatmounts.
Intravitreal injection of paraquat (0.75 μM) 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-α, iNOS, IL-1β, 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 CX3CR1gfp/gfp mice than in CX3CR1gfp/+ mice.
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.
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