Knox, John, Bou-Gharios, George 
ORCID: 0000-0002-9563-9418, Hamill, Kevin J ORCID: 0000-0002-7852-1944 and Willoughby, Colin E
(2022)
MiR-18a-5p Targets Connective Tissue Growth Factor Expression and Inhibits Transforming Growth Factor beta 2-Induced Trabecular Meshwork Cell Contractility.
GENES, 13 (8).
1500-.
Abstract
Increased trabecular meshwork (TM) cell and tissue contractility is a driver of the reduced outflow facility and elevation of intraocular pressure (IOP) associated with primary open-angle glaucoma (POAG). Connective tissue growth factor (CTGF) is an established mediator of TM cell contractility, and its expression is increased in POAG due to transforming growth factor β 2 (TGFβ2) signalling. Inhibiting CTGF upregulation using microRNA (miRNA) mimetics could represent a new treatment option for POAG. A combination of in silico predictive tools and a literature review identified a panel of putative CTGF-targeting miRNAs. Treatment of primary human TM cells with 5 ng/mL TGFβ2 for 24 h identified miR-18a-5p as a consistent responder, being upregulated in cells from five different human donors. Transfection of primary donor TM cells with 20 nM synthetic miR-18a-5p mimic reduced TGFβ2-induced CTGF protein expression, and stable lentiviral-mediated overexpression of this miRNA reduced TGFβ2-induced contraction of collagen gels. Together, these findings identify miR-18a-5p as a mediator of the TGFβ2 response and a candidate therapeutic agent for glaucoma via its ability to inhibit CTGF-associated increased TM contractility.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | glaucoma, primary open-angle glaucoma, microRNAs, connective tissue growth factor (CTGF), TGF beta, intraocular pressure, trabecular meshwork, therapeutics |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 01 Nov 2022 14:49 |
| Last Modified: | 18 Jan 2023 19:48 |
| DOI: | 10.3390/genes13081500 |
| Open Access URL: | https://doi.org/10.3390/genes13081500 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3165941 |
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