Fig. 4: Macrophages were responsible for visual impairment and RPE disorder.

a Macrophage elimination in HFD mice by clodronate liposomes was confirmed by decreases in F4/80 mRNA in the RPE–choroid. The control treatment was done using control liposomes. b–d Macrophage elimination repressed angiotensinogen and AT1R (b) and reduced ox-LDL (c) and the inflammatory cytokines IL-1β, TNFα, and VEGF (d) in the RPE–choroid. e EM showed that abnormal fingerprint profiles (arrows), representing lysosomal deficiency, in the RPE were rare in the absence of macrophages. Control liposomes did not cause any differences in ND mice. f Representative ERG waveforms from individual mice, the amplitudes, and implicit times of a- and b-waves at 1 month. Visual function was preserved in HFD mice when macrophages were eliminated. HFD high-fat diet, RPE retinal pigment epithelium, AT1R angiotensin II type 1 receptor, EM electron microscopy, ERG electroretinogram. Respective numbers for ND mice treated with control, ND mice treated with clodronate, HFD mice treated with control, and HFD mice treated with clodronate were a, c 10, 8, 10, 10; b, d 6, 8, 10, 10; e n = 10 for each group; f n = 5 for each group. The samples were all biologically independent. Data were expressed as means ± standard deviation; *P < 0.05, **P < 0.01. Scale bar, 5.0 μm.