RGD Reference Report - Paraquat-induced retinal degeneration is exaggerated in CX3CR1-deficient mice and is associated with increased retinal inflammation. - Rat Genome Database

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Paraquat-induced retinal degeneration is exaggerated in CX3CR1-deficient mice and is associated with increased retinal inflammation.

Authors: Chen, M  Luo, C  Penalva, R  Xu, H 
Citation: Chen M, etal., Invest Ophthalmol Vis Sci. 2013 Jan 23;54(1):682-90. doi: 10.1167/iovs.12-10888.
RGD ID: 9375525
Pubmed: PMID:23299473   (View Abstract at PubMed)
DOI: DOI:10.1167/iovs.12-10888   (Journal Full-text)

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 muM) 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. RESULTS: Intravitreal injection of paraquat (0.75 muM) 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-1beta, 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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Inflammation  ISOCx3cr1 (Mus musculus)9375525; 9375525 RGD 
Inflammation  IMP 9375525 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cx3cr1  (C-X3-C motif chemokine receptor 1)

Genes (Mus musculus)
Cx3cr1  (C-X3-C motif chemokine receptor 1)

Genes (Homo sapiens)
CX3CR1  (C-X3-C motif chemokine receptor 1)


Additional Information