September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Effect of intravitreal injection of microRNA-146a on ocular inflammation in Lewis rats with experimental autoimmune anterior uveitis
Author Affiliations & Notes
  • Chang-Hao Yang
    Ophthalmology, National Taiwan University Hospital, Taipei, Taiwan
  • Footnotes
    Commercial Relationships   Chang-Hao Yang, None
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    Support  none
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 1873. doi:
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      Chang-Hao Yang; Effect of intravitreal injection of microRNA-146a on ocular inflammation in Lewis rats with experimental autoimmune anterior uveitis. Invest. Ophthalmol. Vis. Sci. 2016;57(12):1873.

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose : The interaction of microRNAs and transcription factor NF-kappaB can regulate the immune response and play an important role in the pathogenesis of uveitis. This study aimed to evaluate the effect of intravitreal injection of microRNA-146a on ocular inflammation in an animal model of experimental autoimmune anterior uveitis (EAAU).

Methods : EAAU was induced in Lewis rats using bovine melanin-associated antigen. The animals received intravitreal injections of 0.5 microg, 1.5 microg miR-146a mimic, or antagomir, immediately before EAAU induction and one week later. Animals were sacrificed 15 days after induction and the inflammatory activity of the anterior chamber was clinically scored, and leukocytes in the aqueous humor were quantified. RNA was extracted from the iris/ciliary bodies to reveal the dynamic changes of eight target miRNAs (miR-155-5p, miR-146a-5p, miR-182-5p, miR-183-5p, miR-147b, miR-21-5p, miR-9-3p, and miR-223-3p) and six cytokine mRNAs (IFN-gamma, IL-17, IL-12A, IL-1beta, IL-6, and IL-10). In situ hybridization of miRNA and enzyme-linked immunosorbent assay quantification of cytokines were performed to confirm the results. Electrophoretic mobility assay (EMSA) was used to evaluate the activation of NF-kappaB.

Results : Disease activity and leukocyte quantification were maximum at day 15 after immunizationin in the control animals. Intravitreal injections of 0.5 mg and 1.5 mg miR-146a significantly inhibited the ocular inflammation in a dose dependent manner. miRNA revealed downregulation of miR-9-3p and upregulation of miR-223-3p, . Cytokine analysis revealed decreased expression of IFN-gamma, IL-17, IL-12A, IL-1beta, and IL-6. EMSA showed decreased NF-kappaB activation.

Conclusions : Intravitreal injection of microRNA-146a significantly suppressed the ocular inflammation in Lewis rats with EAAU. miR146a could regulate the NF-kappaB dependent ocular immune response and might be useful target of therapeuticintervention of uveitis.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.


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