Brimonidine Reduces TGF-beta-induced Extracellular Matrix Synthesis in Human Tenon's Fibroblasts
Overview
Affiliations
Background: Brimonidine is a highly selective α2 adrenergic agonist that has been widely used in anti-glaucoma eyedrops. The aim of this study was to investigate its putative anti-fibrotic role in the fibrosis caused by activated Tenon's fibroblasts.
Methods: Primary cultured human Tenon's fibroblasts were exposed to 2.0 ng/mL of transforming growth factor-β1 (TGF-β1) for up to 48 h. In the presence of various concentrations of brimonidine (from 0.0 to 10.0 μM), the expression levels of fibronectin, collagen types I and III, and β-actin were determined by Western immunoblots. The expression of phosphorylated SMAD2/3 (p-SMAD2/3) was then evaluated using immunofluorescence.
Results: TGF-β1 significantly increased the synthesis of fibronectin and collagens in human Tenon's fibroblasts; however brimonidine treatment distinctly attenuated the TGF-β1-induced production of extracellular matrix (ECM) proteins. TGF-β1 also changed the cellular morphology to be plump, while brimonidine treatment returned the cells to a spindle shape, similar to control fibroblasts. Regarding p-SMAD2/3, brimonidine treatment did not show any apparent changes in its expression.
Conclusions: Our data revealed that brimonidine reduces TGF-β-induced ECM synthesis in human Tenon's fibroblasts in vitro. This finding implies that topical administration of brimonidine may be helpful in reducing the fibrosis caused by the long-term use of topical anti-glaucoma medications.
Watanabe M, Sato T, Tsugeno Y, Higashide M, Furuhashi M, Umetsu A Bioengineering (Basel). 2022; 9(7).
PMID: 35877361 PMC: 9312232. DOI: 10.3390/bioengineering9070310.
Elucidating the Therapeutic Potential of Cell-Penetrating Peptides in Human Tenon Fibroblast Cells.
Chatterjee A, Ansar S, Gopal D, Vetrivel U, George R, Narayanan J ACS Omega. 2022; 7(19):16536-16546.
PMID: 35601335 PMC: 9118429. DOI: 10.1021/acsomega.2c00701.
Zhao Y, Zhang F, Pan Z, Luo H, Liu K, Duan X Cell Death Dis. 2019; 10(8):594.
PMID: 31391457 PMC: 6685939. DOI: 10.1038/s41419-019-1829-1.
Narikawa M, Umemura M, Tanaka R, Fujita T, Yokoyama U, Ishigami T Sci Rep. 2018; 8(1):6277.
PMID: 29674727 PMC: 5908876. DOI: 10.1038/s41598-018-24749-6.
Feng Z, Zhang X, Zhao J, Ma J Int J Ophthalmol. 2017; 10(12):1805-1811.
PMID: 29259896 PMC: 5733505. DOI: 10.18240/ijo.2017.12.03.