Genome-Wide RNA Sequencing of Human Trabecular Meshwork Cells Treated with TGF-β1: Relevance to Pseudoexfoliation Glaucoma

Anton W Roodnat, Breedge Callaghan, Chelsey Doyle, Megan Henry, Katarzyna Goljanek-Whysall, David A Simpson, Carl Sheridan, Sarah D Atkinson, Colin E Willoughby

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Abstract

Pseudoexfoliation glaucoma (XFG) is an aggressive form of secondary open angle glaucoma, characterised by the production of exfoliation material and is estimated to affect 30 million people worldwide. Activation of the TGF-β pathway by TGF-β1 has been implicated in the pathogenesis of pseudoexfoliation glaucoma. To further investigate the role of TGF-β1 in glaucomatous changes in the trabecular meshwork (TM), we used RNA-Seq to determine TGF-β1 induced changes in the transcriptome of normal human trabecular meshwork (HTM) cells. The main purpose of this study was to perform a hypothesis-independent RNA sequencing analysis to investigate genome-wide alterations in the transcriptome of normal HTMs stimulated with TGF-β1 and investigate possible pathophysiological mechanisms driving XFG. Our results identified multiple differentially expressed genes including several genes known to be present in exfoliation material. Significantly altered pathways, biological processes and molecular functions included extracellular matrix remodelling, Hippo and Wnt pathways, the unfolded protein response, oxidative stress, and the antioxidant system. This cellular model of pseudoexfoliation glaucoma can provide insight into disease pathogenesis and support the development of novel therapeutic interventions.
Original languageEnglish
Article number1693
Number of pages28
JournalBiomolecules
Volume12
Issue number11
Early online date15 Nov 2022
DOIs
Publication statusPublished online - 15 Nov 2022

Bibliographical note

Funding: This research was funded by Glaucoma UK (formerly the International Glaucoma Association), UK and Eire Glaucoma Society (UKEGS) and Mason Medical Research Foundation.

Keywords

  • exfoliation glaucoma
  • pseudoexfoliation glaucoma
  • Sequence Analysis, RNA
  • Glaucoma - genetics - metabolism
  • exfoliation syndrome
  • Transforming Growth Factor beta1 - genetics - metabolism
  • transcriptome
  • RNA - metabolism
  • Trabecular Meshwork - metabolism
  • RNA-Seq
  • Humans
  • pseudoexfoliation syndrome
  • trabecular meshwork
  • open-angle glaucoma
  • Trabecular Meshwork/metabolism
  • RNA/metabolism
  • Glaucoma/genetics

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