CX3CR1-dependent subretinal microglia cell accumulation is associated with cardinal features of age-related macular degeneration
J. Clin. Invest. Christophe Combadière, et al. 117:2920 doi:10.1172/JCI31692 [
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Figure 4SrMC accumulation induces retinal degeneration in albino CX3CR1
–/– mice.
(
A and
B) RPE flatmounts of albino CX3CR1
+/+ BALB/c (
A) and CX3CR1
–/– BALB/c mice (
B) showed more numerous CD11b-positive (green) SrMC abutting the RPE (Phalloidin, red) in CX3CR1-deficient animals. (
C) Quantification of subretinal CD11b-positive cells on RPE flatmounts revealed a significantly higher density of MCs in CX3CR1
–/– mice at 1 and 2 months of age raised in ambient light conditions. CX3CR1
–/– BALB/c mice raised in complete darkness showed significantly fewer SrMC than ambient light–raised CX3CR1
–/– BALB/c mice. (
D–
F) Toluidine blue–stained epoxy retinal semithin sections showed complete degeneration of all photoreceptors in albino CX3CR1
–/– BALB/c mice (
E) at 4 months of age compared with CX3CR1
+/+ BALB/c mice (
D). This degeneration was prevented in CX3CR1
–/– BALB/c mice raised in darkness (
F). (
G) Measurements of photoreceptor cell layer thickness showed significant and progressive degeneration in albino CX3CR1
–/– BALB/c mice, which was completely reversed by raising CX3CR1
–/– BALB/c mice in darkness. Experiments were performed on 8–10 eyes from different mice per group. *
P < 0.05. Scale bars: 50 μm.