title: CX3CR1-dependent subretinal microglia cell accumulation is associated with cardinal features of age-related macular degeneration.
abstract: The role of retinal microglial cells (MCs) in age-related macular degeneration (AMD) is unclear. Here we demonstrated that all retinal MCs express CX3C chemokine receptor 1 (CX3CR1) and that homozygosity for the CX3CR1 M280 allele, which is associated with impaired cell migration, increases the risk of AMD. In humans with AMD, MCs accumulated in the subretinal space at sites of retinal degeneration and choroidal neovascularization (CNV). In CX3CR1-deficient mice, MCs accumulated subretinally with age and albino background and after laser impact preceding retinal degeneration. Raising the albino mice in the dark prevented both events. The appearance of lipid-bloated subretinal MCs was drusen-like on funduscopy of senescent mice, and CX3CR1-dependent MC accumulation was associated with an exacerbation of experimental CNV. These results show that CX3CR1-dependent accumulation of subretinal MCs evokes cardinal features of AMD. These findings reveal what we believe to be a novel pathogenic process with important implications for the development of new therapies for AMD.
authors.affiliation: INSERM U543, Laboratoire d'Immunologie Cellulaire, Paris, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Combadière
authors.forename: Charles
authors.initials: C
authors.lastname: Feumi
authors.forename: William
authors.initials: W
authors.lastname: Raoul
authors.forename: Nicole
authors.initials: N
authors.lastname: Keller
authors.forename: Mathieu
authors.initials: M
authors.lastname: Rodéro
authors.forename: Adeline
authors.initials: A
authors.lastname: Pézard
authors.forename: Sophie
authors.initials: S
authors.lastname: Lavalette
authors.forename: Marianne
authors.initials: M
authors.lastname: Houssier
authors.forename: Laurent
authors.initials: L
authors.lastname: Jonet
authors.forename: Emilie
authors.initials: E
authors.lastname: Picard
authors.forename: Patrice
authors.initials: P
authors.lastname: Debré
authors.forename: Mirna
authors.initials: M
authors.lastname: Sirinyan
authors.forename: Philippe
authors.initials: P
authors.lastname: Deterre
authors.forename: Tania
authors.initials: T
authors.lastname: Ferroukhi
authors.forename: Salomon-Yves
authors.initials: SY
authors.lastname: Cohen
authors.forename: Dominique
authors.initials: D
authors.lastname: Chauvaud
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Jeanny
authors.forename: Sylvain
authors.initials: S
authors.lastname: Chemtob
authors.forename: Francine
authors.initials: F
authors.lastname: Behar-Cohen
authors.forename: Florian
authors.initials: F
authors.lastname: Sennlaub
mesh_terms: D000483:Alleles; D000818:Animals; D000073883:CX3C Chemokine Receptor 1; D002465:Cell Movement / Q000235:genetics; D020256:Choroidal Neovascularization / Q000235:genetics / Q000473:pathology; D006720:Homozygote; D006801:Humans; D008268:Macular Degeneration / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism / Q000473:pathology*; D011110:Polymorphism, Genetic; D019707:Receptors, Chemokine / Q000235:genetics*; D012160:Retina / Q000378:metabolism / Q000473:pathology*; D015593:Retinal Drusen / Q000235:genetics / Q000473:pathology
chemical_list: D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; D019707:Receptors, Chemokine