June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
TGFβ1 regulated gene expression in the trabecular meshwork
Author Affiliations & Notes
  • Breedge Conwell
    Biomedical Research Institute, Ulster University, Coleraine, Londonderry, United Kingdom
  • Chelsey Doyle
    Biomedical Research Institute, Ulster University, Coleraine, Londonderry, United Kingdom
  • Anton Roodnat
    Biomedical Research Institute, Ulster University, Coleraine, Londonderry, United Kingdom
  • Megan Henry
    Biomedical Research Institute, Ulster University, Coleraine, Londonderry, United Kingdom
  • Katarzyna Goljanek-Whysall
    School of Medicine, Physiology,, National University of Ireland Galway, Galway, Galway, Ireland
    Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, Liverpool, United Kingdom
  • Sarah D. Atkinson
    Northern Ireland Centre for Stratified Medicine, Ulster University, Londonderry, Londonderry, United Kingdom
  • David Simpson
    Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, Belfast, United Kingdom
  • Colin E Willoughby
    Biomedical Research Institute, Ulster University, Coleraine, Londonderry, United Kingdom
    Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, Liverpool, United Kingdom
  • Footnotes
    Commercial Relationships   Breedge Conwell, None; Chelsey Doyle, None; Anton Roodnat, None; Megan Henry, None; Katarzyna Goljanek-Whysall, None; Sarah D. Atkinson, None; David Simpson, None; Colin Willoughby, None
  • Footnotes
    Support  Fight for Sight (UK) and Glaucoma UK (UK and Eire Glaucoma Society)
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 1634. doi:
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      Breedge Conwell, Chelsey Doyle, Anton Roodnat, Megan Henry, Katarzyna Goljanek-Whysall, Sarah D. Atkinson, David Simpson, Colin E Willoughby; TGFβ1 regulated gene expression in the trabecular meshwork. Invest. Ophthalmol. Vis. Sci. 2021;62(8):1634.

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

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Abstract

Purpose : Transforming growth factor beta (TGFβ) is a profibrotic cytokine that has been implicated in several disease processes such as cellular growth, differentiation, and extracellular matrix (ECM) synthesis. High levels of both latent and active TGFβ1 are prominent in the aqueous humour of patients with pseudo-exfoliation glaucoma (PXFG). The exact relationship between TGFβ1 induced gene regulation and outflow dysfunction in the TM, contributing to glaucoma development, remains unclear. Here we investigated differential changes in gene expression induced by TGFβ1 in a cell-based model of PXFG.

Methods : Primary normal trabecular meshwork cells isolated from donor human corneal rims (n=5) were treated with 5ng/mL TGFβ1 for 24 hours. RNA was extracted using the Qiagen AllPrep kit and RNA-sequencing was performed commercially. Sequencing libraries were generated using NEBNext® Ultra TM RNA Library Prep Kit on the Illumina platform. Bioconductor was used for primary gene mapping and differential expression. Gene pathways and interaction were analysed using DAVID, Reactome and Cytoscape. Genes from enriched pathways that appeared significant in all three databases were explored.

Results : RNA-sequencing analysis identified a total of 532 significantly (p<0.05) upregulated and 480 downregulated genes in primary TM cells in response to TGFβ1. Significantly differentially expressed genes with a fold increase ≥1.5 (n=147) were subjected to a GO and KEGG enrichment analysis. High-ranking gene pathway interactions included TGFβ (PAdj 4×10-03) and SMAD transduction (PAdj 4.9e-07) signalling, ECM organisation (PAdj 6.1×10-07) and cell to cell communication (PAdj 3×10-04) which strongly correlate to glaucoma.

Conclusions : The interaction between the differentially expressed genes and corresponding pathways, in response to TGFβ1, may play a critical role in PXFG development. Further exploration of the role of the TGFβ1 driven gene expression and pathway activation may elucidate the molecular mechanisms involved in PXFG and aid therapeutic development.

This is a 2021 ARVO Annual Meeting abstract.

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