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Novel gene targets for miRNA146a and miRNA155 in anterior uveitis

Micheal O'Rourke1, Michelle Trenkmann2, Mary Connolly2

  • 1Department of Ophthalmology, Royal College of Surgeons in Ireland, Royal Victoria Eye and Ear Hospital, Dublin, Ireland maorourk@tcd.ie.

The British Journal of Ophthalmology
|October 10, 2018
PubMed
Abstract

Insights

This study found increased levels of specific microRNAs (miRNAs) in anterior uveitis (AU). These findings implicate novel miRNA targets in the pathogenesis of this common intraocular inflammation.

Area of Science:

  • Ophthalmology
  • Immunology
  • Molecular Biology

Background:

  • Anterior uveitis (AU) is the most common form of intraocular inflammation.
  • MicroRNAs (miRNAs) are key regulators of gene expression with roles in disease pathogenesis.
  • Understanding miRNA involvement in AU can reveal underlying molecular mechanisms.

Purpose of the Study:

  • To investigate miRNA expression profiles in AU.
  • To identify functional roles and target genes of dysregulated miRNAs in AU pathogenesis.
  • To explore the regulatory pathways influencing miRNA expression in AU.

Main Methods:

  • Peripheral blood mononuclear cells (PBMC) from AU patients and healthy controls (HC) were analyzed for miRNA expression using real-time PCR.
  • Regulation of miRNAs by inflammatory stimuli (TLR1/2, TLR3, TLR4, IL1β, TNFα) and their cytokine outputs were quantified.
  • Functional effects of miRNA overexpression were assessed in THP1 cells, and target genes were identified computationally and experimentally.

Main Results:

  • Overexpression of miRNA146a, miRNA155, and miRNA125a-5p was observed in AU PBMC compared to HC.
  • miRNA155 expression increased with TLR1/2 and TLR4 stimulation, while miRNA146a increased with IL1β.
  • Novel targets for miRNA146a (CD80, PRKCE, VASN) and miRNA155 (SMAD2, TYRP1, FBXO22) were identified.

Conclusions:

  • This study demonstrates the overexpression of proinflammatory miRNA155, regulatory miRNA146a, and miRNA125a-5p in anterior uveitis.
  • Identified novel miRNA targets provide insights into the molecular pathways driving AU.
  • These findings contribute to understanding the pathogenesis of intraocular inflammation.
Keywords:
experimental-laboratorygeneticsimmunologyinflammation

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