September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Transforming Growth Factor-β2 Regulated Expression of microRNAs (miRNAs) in Normal and Glaucomatous Human Optic Nerve Head Cells
Author Affiliations & Notes
  • Tara Tovar-Vidales
    North Texas Eye Research Institute, University of North Texas Hlth Sci Ctr, Fort Worth, Texas, United States
  • Abbot F Clark
    North Texas Eye Research Institute, University of North Texas Hlth Sci Ctr, Fort Worth, Texas, United States
  • Footnotes
    Commercial Relationships   Tara Tovar-Vidales, None; Abbot Clark, Aerie Pharmaceuticals (C), Genzyme (C), ISIS Pharmaceuticals (C), NiCox Research Institute (F), Reata Pharmaceuticals (F), Sanofi-FOVEA (C)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 6001. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to Subscribers Only
      Sign In or Create an Account ×
    • Get Citation

      Tara Tovar-Vidales, Abbot F Clark; Transforming Growth Factor-β2 Regulated Expression of microRNAs (miRNAs) in Normal and Glaucomatous Human Optic Nerve Head Cells. Invest. Ophthalmol. Vis. Sci. 2016;57(12):6001.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Glaucoma is associated with elevated levels of the profibrotic cytokine transforming growth factor-β2 (TGF-β2). TGF-β2 has been implicated in glaucoma damage to the optic nerve head (ONH), which undergoes changes such as increased ECM synthesis and deposition. The disruption of the normal balance between ECM deposition and degradation have an important role in the integrity of the ONH. ONH studies have focused on the regulators of the ECM including matrix metalloproteinases, growth factors, and cross-linking enzymes. However, miRNAs have added additional complexity as post-transcriptional regulators of gene expression that modulate cell functions. The purpose of this study was to determine: (a) whether there are differences in expression of miRNAs between normal and glaucoma ONH cells, (b) whether expression of ONH cell miRNAs are regulated by TGF-β2 and (c) differentially expressed miRNA target predictions.

Methods : Primary human ONH cell strains from normal (NONH=3) and glaucomatous (GONH=3) donor eyes were grown to 100% confluency and treated with or without TGF-β2 (5ng/ml) for 24 hours. RNA was isolated and cDNA synthesis performed and subjected to miRNA PCR arrays. miRNA target predictions were based on the miRanda algorithm.

Results : The miRNA PCR arrays were analyzed and comparisons were made between NONH and GONH cells and most of the affected miRNAs were down regulated (hsa-miR-9-5p, hsa-miR-32-5p, hsa-Let-7c, hsa-Let-7f-5p, and hsa-miR-124-3p). NONH cells exposed to TGF-β2 showed that the most affected miRNA was up regulated (hsa-miR-424-5p). GONH cells exposed to TGF-β2 showed that the most affected miRNAs were down regulated (hsa-miR-9-5p, hsa-miR-26b-5p, hsa-miR-200c-3p). The most prominent targets of miRNAs included LOX and gremlin, which previously were shown to have altered expression in GONH cells or with TGF-β2 treatment.

Conclusions : These data indicate that miRNAs are expressed by ONH cells and may be regulated by TGF-β2. Therefore, miRNAs may target BMP antagonist proteins and cross-linking enzymes to modify the ECM in the ONH. These results may provide a new understanding on the role of miRNA epigenetics in molecular pathogenesis of the ONH.

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

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×