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Fig. 1 | Acta Neuropathologica Communications

Fig. 1

From: Regulating microglial miR-155 transcriptional phenotype alleviates Alzheimer’s-induced retinal vasculopathy by limiting Clec7a/Galectin-3+ neurodegenerative microglia

Fig. 1

Targeting microglial miR-155 diminished the population of Clec7a+ MGnD microglia. a Schema for generation of wild type (WT) and Alzheimer’s disease (AD) mice that were specifically targeted for miR-155 in microglia. miR-155 fl/fl:APP/PS1 mice and miR-155 fl/fl:Cx3cr1CreERT2 mice were crossed to create APP/PS1:miR155cKO mice. Other experimental groups include APP/PS1, WT:miR155cKO and WT. Two consecutive doses of tamoxifen (150 mg/kg) were introduced peritoneally to 1.5-month-old mice to induce conditional microglial miR-155 knock-out. Mice were sacrificed at 4 months or 8 months for cross-section, vascular isolation, flat mount, mass spectrometry (MS), western blotting (WB) and Meso Scale Discovery (MSD). This illustration was created by using Biorender.com. be Representative images of immunofluorescent staining for Clec7a+ microglia (red), Tmem119+ microglia (green) and lectin for blood vessels (blue) on retinal flat mounts from b APP/PS1 genotype, ganglion cell layer (GCL) to inner plexiform layer (IPL); c APP/PS1 genotype, outer plexiform layer (OPL); d WT genotype, GCL to IPL; and e APP/PS1:miR155cKO genotype, GCL to IPL. Images were obtained using 20 × microscope objectives. Arrows indicate Clec7a+ microglia. Scale bars = 10 µm. f Manual counting of Clec7a+ microglia in each entire retinal cross-section from all experimental groups (n = 48 total, n = 6 each group). g Ratio of Clec7a+ microglia to Iba1+ microglia from the same mouse cohort. Data from individual mice (circles) as well as group means ± SEMs are shown. Black-filled circles represent male and clear circles represent female animals. *p < 0.05, **p < 0.01, ***p < 0.001, by three-way ANOVA with Tukey’s post-hoc multiple comparison test. Two group statistical analysis was performed using an unpaired two-tailed Student t-test and is shown in parentheses. Fold changes and percentage decreases are shown in red

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