Paraquat-Induced Retinal Degeneration Is Exaggerated in CX3CR1-Deficient Mice and Is Associated with Increased Retinal Inflammation
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08/01/2013
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Resumo |
PURPOSE:<br/>To investigate the role of the Fractalkine receptor CX3CR1 pathway in oxidative insults-mediated retinal degeneration and immune activation.<br/>METHODS:<br/>A prooxidant, paraquat (0.75 µM) 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 RT-PCR. Microglial activation and immune cell infiltration were examined by confocal microscopy of retinal flatmounts.<br/>RESULTS:<br/>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-a, iNOS, IL-1ß, 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.<br/>CONCLUSIONS:<br/>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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Idioma(s) |
eng |
Direitos |
info:eu-repo/semantics/restrictedAccess |
Fonte |
Chen , M , Luo , C , Penalva , R & Xu , H 2013 , ' Paraquat-Induced Retinal Degeneration Is Exaggerated in CX3CR1-Deficient Mice and Is Associated with Increased Retinal Inflammation ' Investigative Opthalmology and Visual Science , vol 54 , no. 1 , pp. 682-90 . DOI: 10.1167/iovs.12-10888 |
Palavras-Chave | #/dk/atira/pure/subjectarea/asjc/2700/2731 #Ophthalmology #/dk/atira/pure/subjectarea/asjc/2800/2809 #Sensory Systems #/dk/atira/pure/subjectarea/asjc/2800/2804 #Cellular and Molecular Neuroscience |
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article |