title: Paraquat-induced retinal degeneration is exaggerated in CX3CR1-deficient mice and is associated with increased retinal inflammation.
abstract: OBJECTIVE
  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 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.
  
  
  RESULTS
  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 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.
authors.affiliation: Centre for Vision and Vascular Science, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Northern Ireland, United Kingdom.
authors.forename: Mei
authors.initials: M
authors.lastname: Chen
authors.forename: Chang
authors.initials: C
authors.lastname: Luo
authors.forename: Rosana
authors.initials: R
authors.lastname: Penalva
authors.forename: Heping
authors.initials: H
authors.lastname: Xu
mesh_terms: D000818:Animals; D000073883:CX3C Chemokine Receptor 1; D004247:DNA / Q000235:genetics*; D004195:Disease Models, Animal; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D005786:Gene Expression Regulation; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D018384:Oxidative Stress; D010269:Paraquat / Q000633:toxicity; D060888:Real-Time Polymerase Chain Reaction; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics*; D012160:Retina / Q000378:metabolism / Q000473:pathology*; D012162:Retinal Degeneration / Q000139:chemically induced* / Q000150:complications / Q000235:genetics; D012173:Retinitis / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000073883:CX3C Chemokine Receptor 1; C471885:Cx3cr1 protein, mouse; D019707:Receptors, Chemokine; D004247:DNA; D010269:Paraquat