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 [Go to this article.]

Figure 3
SrMCs accumulate in CX3CR1^–/– C57BL/6 mice with age and lead to retinal degeneration. (A) Sections from an 18-month-old CX3CR1^+/GFP mouse showed GFP-positive cells in close proximity to Griffonia simplicifolia–positive (red) retinal endothelial cells. (B) Sections from an 18-month-old CX3CR1^GFP/GFP mouse revealed the same distribution of GFP-positive cells in the inner retina but showed additional subretinal GFP-positive cells juxtaposed to the RPE cell layer (arrows). (C and D) Confocal images of the outer plexiform layer revealed that the entire network of ramified MCs was GFP positive and similarly dense in CX3CR1^+/GFP (C) and CX3CR1^GFP/GFP mice (D). (E and F) RPE flatmounts of aged mice showed a strong accumulation of SrMCs in CX3CR1^+/GFP (E) and CX3CR1^GFP/GFP mice (F). (G) Quantification of subretinal GFP-positive cells on RPE flatmounts revealed that SrMCs accumulated progressively in CX3CR1^GFP/GFP mice and were significantly more numerous than in CX3CR1^+/GFP mice at all time points. (H and I) Toluidine blue–stained epoxy retinal semithin sections showed degeneration of photoreceptors in 18-month-old CX3CR1^–/– (I) mice compared with CX3CR1^+/+ (H) mice. (J) Measurements of photoreceptor cell layer thickness showed significant thinning of the photoreceptor cell layer in CX3CR1^–/– mice compared with CX3CR1^+/+ mice. Experiments were performed on 4–8 eyes from different mice per group. *P < 0.05. Ch, choroid. ROS, rod OS. Scale bars: 50 μm.