April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
MicroRNA Modulation Of Innate Immune Response In The Retina
Author Affiliations & Notes
  • MinHee K. Ko
    Opthalmic Pathology,
    Doheny Eye Institute, Los Angeles, California
  • Narsing A. Rao
    Ophthalmology,
    Doheny Eye Institute, Los Angeles, California
  • Footnotes
    Commercial Relationships  MinHee K. Ko, None; Narsing A. Rao, None
  • Footnotes
    Support  NIH Grant EY019506, EY017347, EY03040, and RPB
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 2941. doi:
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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)

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Abstract

Purpose: : 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.

Methods: : 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.

Results: : 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.

Conclusions: : 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.

Keywords: gene microarray • retina • immunomodulation/immunoregulation 
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