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

Samin Hong,Sueng-Han Han,Gong Je Seong,Yoo Kyung Song,Chan Yun Kim,Kang Yoon Kim

doi:10.1186/s12886-015-0045-8

Abstract

BackgroundBrimonidine 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.MethodsPrimary 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.ResultsTGF-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.ConclusionsOur 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12886-015-0045-8) contains supplementary material, which is available to authorized users.

Highlights

Brimonidine is a highly selective α2 adrenergic agonist that has been widely used in anti-glaucoma eyedrops
Some previous reports dealt with the adverse effects of perioperative use of brimonidine for laser in situ keratomileusis (LASIK) [8,9,10]
Topical administration of brimonidine was found to raise the incidence of corneal flap dislocation after LASIK and Walter and Gilbert [8] suggested the following possible mechanisms: (1) brimonidine itself or brimonidine-containing eyedrops may act as a lubricant and cause the flap to slide from the corneal bed, (2) brimonidine may cause vasoconstriction of the anterior ocular vessels and decrease the corneal endothelial function to maintain proper flap adherence, and (3) brimonidine itself may be directly toxic to the corneal endothelial cells and reduce their metabolic activity

Summary

Introduction

Brimonidine is a highly selective α2 adrenergic agonist that has been widely used in anti-glaucoma eyedrops. Though many anti-glaucoma eyedrops have been reported to induce conjunctival and/or subconjunctival fibrosis [1,2,3], information about the effects of brimonidine in this process remains scarce. Brimonidine is a highly selective α2 adrenergic agonist that has been widely used as an anti-glaucoma ophthalmic solution [4,5,6,7]. It reduces intraocular pressure (IOP) by decreasing production of aqueous humor and increasing uveoscleral outflow. The precise mechanisms of this phenomenon have not yet been proven

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