The TGFβ Induced MicroRNAome of the Trabecular Meshwork

Chelsey Doyle, Breedge Callaghan, Anton W. Roodnat, Lee Armstrong, Karen Lester, David A. Simpson, Sarah D. Atkinson, Carl Sheridan, Declan J. McKenna, Colin E. Willoughby

Research output: Contribution to journalArticlepeer-review

Abstract

Primary open-angle glaucoma (POAG) is a progressive optic neuropathy with a complex, multifactorial aetiology. Raised intraocular pressure (IOP) is the most important clinically modifiable risk factor for POAG. All current pharmacological agents target aqueous humour dynamics to lower IOP. Newer therapeutic agents are required as some patients with POAG show a limited therapeutic response or develop ocular and systemic side effects to topical medication. Elevated IOP in POAG results from cellular and molecular changes in the trabecular meshwork driven by increased levels of transforming growth factor β (TGFβ) in the anterior segment of the eye. Understanding how TGFβ affects both the structural and functional changes in the outflow pathway and IOP is required to develop new glaucoma therapies that target the molecular pathology in the trabecular meshwork. In this study, we evaluated the effects of TGF-β1 and -β2 treatment on miRNA expression in cultured human primary trabecular meshwork cells. Our findings are presented in terms of specific miRNAs (miRNA-centric), but given miRNAs work in networks to control cellular pathways and processes, a pathway-centric view of miRNA action is also reported. Evaluating TGFβ-responsive miRNA expression in trabecular meshwork cells will further our understanding of the important pathways and changes involved in the pathogenesis of glaucoma and could lead to the development of miRNAs as new therapeutic modalities in glaucoma.
Original languageEnglish
Article number1060
Pages (from-to)1-32
Number of pages32
JournalCells
Volume13
Issue number12
Early online date19 Jun 2024
DOIs
Publication statusPublished online - 19 Jun 2024

Bibliographical note

Publisher Copyright:
© 2024 by the authors.

Data Access Statement

Data are contained within the article. Raw RNA-Seq data were deposited and released in the SRA database: https://www.ncbi.nlm.nih.gov/sra/PRJNA1099874
(accessed on 8 June 2024).

Keywords

  • glaucoma
  • primary open-angle glaucoma
  • POAG
  • trabecular meshwork
  • intra-ocular pressure
  • pseudoexfoliation glaucoma
  • microRNA
  • miRNA
  • transforming growth factor beta
  • TGFβ
  • fibrosis
  • epigenetics
  • gene therapy
  • therapeutics

Fingerprint

Dive into the research topics of 'The TGFβ Induced MicroRNAome of the Trabecular Meshwork'. Together they form a unique fingerprint.

Cite this