Fig. 4

Conditional microglial miR-155 knock-out enhanced PI3K-Akt signaling in APP/PS1 mouse retinas. a Detectable protein hierarchies displayed as heatmaps from a a comparison of 8-month-old WT and WT:miR-155cKO mice and b a comparison of 8-month-old APP/PS1 and APP/PS1:miR-155cKO mice; upregulated proteins are shown in purple and downregulated proteins in green. c, d Principal component analysis for a and b e–f Volcano plots and top 15 up- or downregulated proteins by fold change between e 8-month-old WT vs. WT:miR-155cKO mice and f 8-month-old APP/PS1 vs. APP/PS1:miR-155cKO mice; upregulated proteins are shown in purple and downregulated proteins in green. g Pie chart of PANTHER functional classification analysis showing fraction and percentage of significantly differentially expressed proteins (DEPs, up- or downregulated proteins) grouped by protein class category based on a comparison of APP/PS1 and APP/PS1:miR-155cKO mice. h Ingenuity pathway analysis (IPA) of canonical pathways based on APP/PS1 vs. APP/PS1:miR-155cKO mice. Several upregulated PI3K-Akt pathways are shown here. P values are labelled on each pathway. Quantities of commonly changed molecules between each two pathways are labelled in red together with highlighted molecules and detectable fold changes. i Z-scores for the IPA analysis of canonical pathways from 8-month-old WT vs. WT:miR-155cKO mice and 8-month-old APP/PS1 and APP/PS1:miR-155cKO mice. j–l Densitometric analysis of western blotting protein bands of j EIF3c, k NDUFA10, and l NDUFA6, each normalized by β-actin control for retinal lysates from all experimental groups (n = 48 total, n = 6 each group). m IPA analysis for upstream regulators Spp1 and Cxcl-8 based on 8-month-old APP/PS1 vs. APP/PS1:miR-155cKO versus mice. Refer to “prediction legend” in the graph for details. Detectable fold changes of DEPs are written next to each molecule. CP-common pathways. n Densitometric analysis of western blotting protein bands of SPP1 normalized by β-actin control for retinal lysates from the same 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, 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