title: Experimental autoimmune uveoretinitis (EAU)-related tissue damage and angiogenesis is reduced in CCL2⁻/⁻CX₃CR1gfp/gfp mice.
abstract: OBJECTIVE
  To investigate the roles of the CCL2-CCR2 and CX₃CL1-CX₃CR1 pathways in experimental autoimmune uveoretinitis (EAU)-mediated retinal tissue damage and angiogenesis.
  
  
  METHODS
  The C57BL/6J wild-type (WT) and CCL2(-/-)CX₃CR1(gfp/gfp) (double knockout [DKO]) mice were immunized with IRBP₁₋₂₀. Retinal inflammation and tissue damage were evaluated clinically and histologically at different days postimmunization (p.i.). Retinal neovascular membranes were evaluated by confocal microscopy of retinal flat mounts, and immune cell infiltration by flow cytometry.
  
  
  RESULTS
  At day 25 p.i., DKO mice had lower clinical and histological scores and fewer CD45(high)CD11b(+) infiltrating cells compared with WT mice. The F4/80(+) macrophages constitute 40% and 21% and CD11b(+)Gr-1(+)Ly6G(+) neutrophils constitute 10% and 22% of retinal infiltrating cells in WT and DKO mice, respectively. At the late stages of EAU (day 60-90 p.i.), DKO and WT mice had similar levels of inflammatory score. However, less structural damage and reduced angiogenesis were detected in DKO mice. Neutrophils were rarely detected in the inflamed retina in both WT and DKO mice. Macrophages and myeloid-derived suppressor cells (MDSCs) accounted for 8% and 3% in DKO EAU retina, and 19% and 10% in WT EAU retina; 71% of infiltrating cells were T/B-lymphocytes in DKO EAU retina and 50% in WT EAU retina.
  
  
  CONCLUSIONS
  Experimental autoimmune uveoretinitis-mediated retinal tissue damage and angiogenesis is reduced in CCL2(-/-)CX₃CR1(gfp/gfp) mice. Retinal inflammation is dominated by neutrophils at the acute stage and lymphocytes at the chronic stage in these mice. Our results suggest that CCR2(+) and CX₃CR1(+) monocytes are both involved in tissue damage and angiogenesis in EAU.
authors.affiliation: Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, United Kingdom.
authors.forename: Jiawu
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, United Kingdom.
authors.forename: Mei
authors.initials: M
authors.lastname: Chen
authors.affiliation: Centre for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, United Kingdom.
authors.forename: Heping
authors.initials: H
authors.lastname: Xu
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D001402:B-Lymphocytes / Q000276:immunology*; D018932:Chemokine CCL2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018925:Chemokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D008264:Macrophages; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000276:immunology; D012313:RNA / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012160:Retina / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D012173:Retinitis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D014605:Uveitis / Q000235:genetics / Q000276:immunology* / Q000473:pathology
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D018925:Chemokines; D012313:RNA
keywords: angiogenesis; autoimmunity; chemokine; retina; uveitis