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- Title
CX3CR1-dependent subretinal microglia cell accumulation is associated with cardinal features of age-related macular degeneration.
- Authors
Combadière, Christophe; Feumi, Charles; Raoul, William; Keller, Nicole; Rodéro, Mathieu; Pézard, Adeline; Lavalette, Sophie; Houssier, Marianne; Jonet, Laurent; Picard, Emilie; Debré, Patrice; Sirinyan, Mirna; Deterre, Philippe; Ferroukhi, Tania; Cohen, Salomon-Yves; Chauvaud, Dominique; Jeanny, Jean-Claude; Chemtob, Sylvain; Behar-Cohen, Francine; Sennlaub, Florian
- 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.
- Publication
The Journal of clinical investigation, 2007, Vol 117, Issue 10, p2920
- ISSN
0021-9738
- Publication type
Journal Article
- DOI
10.1172/JCI31692