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microRNA-34a-Mediated Down-Regulation of the Microglial-Enriched Triggering Receptor and Phagocytosis-Sensor TREM2 in Age-Related Macular Degeneration

Fig 1

Up-regulation of miRNA-34a and down-regulation of TREM2 in AMD whole retina and macular region versus age-matched controls; (A) color-coded cluster diagram; miRNA-34a and miRNA-155 showed the greatest up-regulation to 3.3- and 1.8-fold over their respective controls in whole retina and 8.8- and 1.6-fold over their respective controls in the macular region; a significant up-regulation was not observed for either miRNA-183 or 5S RNA controls in either (B) whole retina or (C) the macular region; one preliminary study involving miRNA-34a up-regulation and a miRNA-34a-mediated TREM2 down-regulation has previously been reported for the hippocampal CA1 region of AD brain [10,12]; miRNA-34a is part of an inducible pro-inflammatory miRNA quintet consisting of miRNA-9, miRNA-34a, miRNA-125b, miRNA-146a, miRNA-155 involved in degeneration in the human CNS; there were no significant differences between age for control or AMD tissues; all AMD cases were for moderate-to-advanced stages of disease; all post-mortem intervals were 2.5 h or less [2022]; there were no significant differences in RNA quality (all RNA integrity numbers—RIN values—were 8.1–9.1) or yield between the control (N = 9) or AMD (N = 12) groups (p >0.05, ANOVA); (D-F) Western blot of TREM2 protein in the same AMD (A) and control (C) tissues in (D) whole retina and (E) the macular region; in whole retina (N = 10) TREM2 protein levels were reduced to 0.54-fold of control levels and in the macular region (N = 5) TREM2 levels were reduced to 0.22-fold of control; (E) note that TREM2 Western blot analysis on 10% TGSDS gels show multiple bands due to the variable post-translational glycosylation of ~25kDa core TREM2 protein (unpublished); TREM2 protein levels are shown as the mean plus one standard deviation (SD) are bar-graphed in (F); see text; *p<0.05; **p<0.001 (ANOVA).

Fig 1