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MinHee K. Ko, Narsing A. Rao; MicroRNA Modulation Of Innate Immune Response In The Retina. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2941.
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© ARVO (1962-2015); The Authors (2016-present)
Toll-like receptors (TLRs), their signaling molecules and proapoptotic genes are activated in retina by innate immune response to complete Freund adjuvant containing heat-inactivated mycobacteria (CFA). We determined the effect of chronic immune response in the retina of animals injected with CFA.
B10.RIII mice were injected subcutaneously with CFA or with incomplete Freund adjuvant (IFA). Retinas of mice examined on day 5 postinjection (p.i.) and of mice repeatedly injected with CFA or IFA (every 4 weeks) for 3 months (M) were submitted for pathway-focused PCR array (SABioscience) or microRNA (miRNA) microarray (Miltenyi Biotech). Retinas of mice repeat injected with CFA or IFA for 3, 6, and 9 M were examined using H&E and TUNEL. For bioinformatic analysis, computational methods such as miRWalk, miRanda, and PicTar were used in addition to Ingenuity Pathways Analysis.
TLRs, their signaling molecules, and apoptotic genes (such as tumor necrosis factor, FAS, Mitogen-activated protein kinases 4, and caspases) were upregulated in retinas examined on day 5 p.i but downregulated in retinas examined at 3 M p.i. There is no significant sign of inflammatory cell infiltration, photoreceptor damage or apoptotic cells in retinas examined at 3, 6, or 9 M. 5-10% of 503 cell-death focused genes were altered. 49% more antiapoptotic genes were upregulated than apoptotic genes, and 54% more apoptotic genes were downregulated than antiapoptotic genes in the retina at 3 M. Of 2223 mature miRNAs, 51 miRNAs were upregulated and 6 miRNAs were downregulated. Sixteen miRNAs were selected after exclusion of miRNAs, which had background signals in noninjected groups. Four miRNAs, miR-9, 181a, 338-3p, and 495, showed 1.5-1.98 fold increases in CFA-injected compared to IFA-injected mice. We also found that the downregulated messenger RNA in PCR array were specifically validated targets of those miRNA.
CFA-mediated innate immune response in acute phase was suppressed in chronic immune response. The result of miRNA microarray suggested that miR-9, 181a, 338-3p, and miR-495 may be involved in suppression of the immune response and apoptotic pathway.
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