Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

The TGFβ Induced MicroRNAome of the Trabecular Meshwork

Chelsey Doyle
ORCID logo ,
Breedge Callaghan
,
Anton W Roodnat
ORCID logo ,
Lee Armstrong
,
Karen Lester
,
David A Simpson
ORCID logo ,
Sarah D. Atkinson
ORCID logo ,
Carl Sheridan
,
Declan J McKenna
ORCID logo ,
Colin E Willoughby
* ORCID logo
Version 1 : Received: 1 May 2024 / Approved: 3 May 2024 / Online: 3 May 2024 (11:22:57 CEST)

How to cite: Doyle, C.; Callaghan, B.; Roodnat, A. W.; Armstrong, L.; Lester, K.; Simpson, D. A.; Atkinson, S. D.; Sheridan, C.; McKenna, D. J.; Willoughby, C. E. The TGFβ Induced MicroRNAome of the Trabecular Meshwork. Preprints 2024, 2024050159. https://doi.org/10.20944/preprints202405.0159.v1 Doyle, C.; Callaghan, B.; Roodnat, A. W.; Armstrong, L.; Lester, K.; Simpson, D. A.; Atkinson, S. D.; Sheridan, C.; McKenna, D. J.; Willoughby, C. E. The TGFβ Induced MicroRNAome of the Trabecular Meshwork. Preprints 2024, 2024050159. https://doi.org/10.20944/preprints202405.0159.v1

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 hu-mour 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 ef-fects 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 TGF affects both the structural and functional changes in the outflow pathway and IOP is required to de-velop new glaucoma therapies that target the molecular pathology in the trabecular meshwork. In this study we evaluated the effects of TGF-1 and -2 treatment on miRNA expression in cultured human primary trabecular meshwork cells. Our findings are pre-sented in terms of specific miRNAs (miRNA-centric), but given miRNAs work in net-works to control cellular pathways and processes, a pathway-centric view of miRNA ac-tion is also reported. Evaluating TGF-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.

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

Subject

Medicine and Pharmacology, Ophthalmology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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