JCI - CX3CR1-dependent subretinal microglia cell accumulation is associated with cardinal features of age-related macular degeneration

CX3CR1-dependent subretinal microglia cell accumulation is associated with cardinal features of age-related macular degeneration

Christophe Combadière, Charles Feumi, William Raoul, Nicole Keller, Mathieu Rodéro, Adeline Pézard, Sophie Lavalette, Marianne Houssier, Laurent Jonet, Emilie Picard, Patrice Debré, Mirna Sirinyan, Philippe Deterre, Tania Ferroukhi, Salomon-Yves Cohen, Dominique Chauvaud, Jean-Claude Jeanny, Sylvain Chemtob, Francine Behar-Cohen, Florian Sennlaub

Published in Volume 117, Issue 10

J Clin Invest. 2007; 117(10):2920–2928 doi:10.1172/JCI31692

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Figure 6

SrMCs accumulate after laser injury, exacerbate neovascularization, and induce adjacent retinal degeneration.

(A and B) At 3 months of age, CX3CR1^+/GFP mice displayed some GFP-positive (green) SrMCs adjacent to the CNV (red, Griffonia simplicifolia) 14 days after laser injury (A), and CX3CR1^GFP/GFP mice showed strong SrMC accumulation (B). (C) CX3CR1^+/GFP mice showed a transient increase of SrMCs after laser impact, peaking at day 7; however, SrMCs in CX3CR1^GFP/GFP mice were significantly more numerous at that time and continued to accumulate. (D–F) Immunohistochemistry at day 7 revealed VEGF expression (green) in F4/80-positive activated CX3CR1^+/+ MCs (red) in the subretinal space. Nuclei were stained with DAPI (blue). (G and H) Micrographs of fluorescein dextran (green) perfused RPE/choroidal flatmounts double labeled with endothelial cell marker Griffonia simplicifolia (red) 14 days after laser impact in CX3CR1^+/+ (G) and CX3CR1^–/– (H) mice showed representative CNV. (I) Quantification showed exacerbated neovascularization in the knockout strains. (J) Eyes of CX3CR1^+/+ mice (12 months old) showed a normal photoreceptor cell layer 200 μm adjacent to the impact 21 days after laser treatment. (K) At this stage CX3CR1^–/– mice displayed SrMCs and a thinned and irregular photoreceptor cell layer. (L) Laser-dependent retinal degeneration (calculated as described in Methods) was significantly more pronounced in CX3CR1^–/– mice only at 100 and 200 μm. Experiments were performed on 8–10 eyes from different mice per group. *P < 0.05. Scale bars: 50 μm (A, B, G, H, J, and K), 10 μm (D–F).