title: Retinal Phenotype following Combined Deletion of the Chemokine Receptor CCR2 and the Chemokine CX3CL1 in Mice.
abstract: OBJECTIVE
  Conflicting data were reported with respect to the retinal phenotype of mice with dual perturbation of the CCL2 and CX3CR1 genes. We report the generation and retinal phenotype of mice with a reverse CCR2/CX3CL1 gene deficiency as a suggested model for age-related macular degeneration (AMD).
  
  
  METHODS
  Crossing of single-deficient mice generated CCR2/CX3CL1 DKO mice. DKO mice were compared with age-matched C57BL6J mice. Evaluation included color fundus photographs, electroretinography (ERG), histology and morphometric analysis. Immunohistochemistry for CD11b in retinal cross-sections and retinal pigment epithelium (RPE)-choroid flat mounts was performed to assess microglia and macrophage recruitment.
  
  
  RESULTS
  A minority of DKO mice showed yellowish subretinal deposits at 10 months. ERG recordings showed reduced cone sensitivity in young, but not older DKO mice. Compared to wild-type mice, DKO mice exhibited 11% reduction in the number of outer nuclear layer nuclei. Old DKO mice had an increased number of CD11b-positive cells across the retina, and on RPE-choroid flat mounts.
  
  
  CONCLUSIONS
  In the absence of the rd8 allele, deficiency of CCR2 and CX3CL1 in mice leads to a mild form of retinal degeneration which is associated with the recruitment of macrophages, particularly to the subretinal space. This model enables to assess consequences of perturbed chemokine signaling, but it does not recapitulate cardinal AMD features.
authors.affiliation: Department of Ophthalmology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Shira
authors.initials: S
authors.lastname: Hagbi-Levi
authors.forename: Michelle
authors.initials: M
authors.lastname: Grunin
authors.forename: Sarah
authors.initials: S
authors.lastname: Elbaz-Hayoun
authors.forename: David
authors.initials: D
authors.lastname: Tal
authors.forename: Alexey
authors.initials: A
authors.lastname: Obolensky
authors.forename: Joel
authors.initials: J
authors.lastname: Hanhart
authors.forename: Eyal
authors.initials: E
authors.lastname: Banin
authors.forename: Tal
authors.initials: T
authors.lastname: Burstyn-Cohen
authors.forename: Itay
authors.initials: I
authors.lastname: Chowers
mesh_terms: D000818:Animals; D054428:Chemokine CX3CL1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D004596:Electroretinography; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia; D010641:Phenotype; D054390:Receptors, CCR2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012160:Retina / Q000473:pathology / Q000503:physiopathology*; D012162:Retinal Degeneration / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D055213:Retinal Pigment Epithelium / Q000378:metabolism / Q000503:physiopathology
chemical_list: D054428:Chemokine CX3CL1; D054390:Receptors, CCR2