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Brimonidine reduces TGF-beta-induced extracellular matrix synthesis in human Tenon's fibroblasts

 Samin Hong  ;  Sueng-Han Han  ;  Chan Yun Kim  ;  Kang Yoon Kim  ;  Yoo Kyung Song  ;  Gong Je Seong 
 BMC OPHTHALMOLOGY, Vol.15 : 54, 2015 
Journal Title
Issue Date
Actins/metabolism ; Adrenergic alpha-2 Receptor Agonists/pharmacology* ; Blotting, Western ; Brimonidine Tartrate/pharmacology* ; Cells, Cultured ; Collagen Type I/metabolism ; Collagen Type III/metabolism ; Extracellular Matrix Proteins/metabolism* ; Fibroblasts/drug effects* ; Fibroblasts/metabolism ; Fibroblasts/pathology ; Fibronectins ; Fibrosis ; Humans ; Tenon Capsule/cytology* ; Transforming Growth Factor beta1/pharmacology*
Fibroblast ; Fibrosis ; Brimonidine ; Transforming growth factor-β ; Glaucoma
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.
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1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Chan Yun(김찬윤) ORCID logo https://orcid.org/0000-0002-8373-9999
Seong, Gong Je(성공제) ORCID logo https://orcid.org/0000-0002-5456-4296
Song, Yoo Kyung(송유경)
Han, Seung Han(한승한) ORCID logo https://orcid.org/0000-0001-8972-4790
Hong, Sa Min(홍사민)
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