MicroRNAs in retina during development of experimental autoimmune uveoretinitis in rats

Br J Ophthalmol. 2016 Mar;100(3):425-31. doi: 10.1136/bjophthalmol-2015-306924. Epub 2015 Nov 5.

Abstract

Purpose: To determine the changes in the expression profiles of microRNAs (miRNAs) in retinas during the development of experimental autoimmune uveoretinitis (EAU) in rats.

Methods: The levels of interleukin-1β (IL-1β) and monocyte chemoattractant protein-1 (MCP-1) were measured in aqueous humour samples and supernatants of homogenised posterior eye cups obtained from Lewis rats immunised with interphotoreceptor retinoid binding protein peptide (R14) and complete Freund's adjuvant. Microarray analysis was performed to determine the miRNA profiles in the retina of eyes with EAU on days 0 (baseline), 7, 14 and 21 after immunisation.

Results: The levels of IL-1β and MCP-1 in the aqueous humour and the supernatants of posterior eye cups were significantly elevated in eyes with EAU, and the levels corresponded with the stage of the EAU. On day 14 after immunisation, the expressions of nine miRNAs (miRNA-223, 142-5p, 142-3p, 21, 146a, 146b, 1949, 1188-3p and 193) were significantly elevated, and the expressions of four miRNAs (miRNA-181a, 183*, 124* and 331) were downregulated relative to the baseline. Quantitative PCR analyses confirmed the elevation of miRNA-223 and miRNA-146 and the downregulation of miRNA-181a in retinas with EAU on day 14 after immunisation. In situ hybridisation confirmed increased expression of miR-223 and miR-146 in retinas with EAU.

Conclusions: Several miRNAs were significantly increased or decreased in retinas during the course of EAU. The expression of miR-223 and miR-146a corresponded with the clinical score of the EAU and elevation of IL-1β/MCP-1 in the eye with EAU. Further studies are required to clarify the role of miRNA in eyes with autoimmune uveoretinitis.

Keywords: Immunology; Inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aqueous Humor / metabolism
  • Autoimmune Diseases / genetics*
  • Autoimmune Diseases / metabolism
  • Autoimmune Diseases / pathology
  • Chemokine CCL2 / metabolism
  • Disease Models, Animal*
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression Profiling
  • Gene Expression Regulation / physiology*
  • In Situ Hybridization
  • Interleukin-1beta / metabolism
  • Male
  • MicroRNAs / genetics*
  • Oligonucleotide Array Sequence Analysis
  • Rats
  • Rats, Inbred Lew
  • Real-Time Polymerase Chain Reaction
  • Retinitis / genetics*
  • Retinitis / metabolism
  • Retinitis / pathology
  • Uveitis / genetics*
  • Uveitis / metabolism
  • Uveitis / pathology

Substances

  • Ccl2 protein, rat
  • Chemokine CCL2
  • Interleukin-1beta
  • MicroRNAs