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Published in: BMC Ophthalmology 1/2015

Open Access 01-12-2015 | Research article

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

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

Published in: BMC Ophthalmology | Issue 1/2015

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Abstract

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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Literature
1.
go back to reference Wu KY, Hong SJ, Wang HZ. Effects of pilocarpine and other antiglaucoma drugs on cultured human Tenon’s fibroblast cells. J Ocul Pharmacol Ther. 1997;13:13–21.CrossRefPubMed Wu KY, Hong SJ, Wang HZ. Effects of pilocarpine and other antiglaucoma drugs on cultured human Tenon’s fibroblast cells. J Ocul Pharmacol Ther. 1997;13:13–21.CrossRefPubMed
2.
go back to reference Lark KK, Pasha AS, Yan X, Edward DP. The effect of latanoprost and brimonidine on rabbit subconjunctival fibroblasts. J Glaucoma. 1999;8:72–6.CrossRefPubMed Lark KK, Pasha AS, Yan X, Edward DP. The effect of latanoprost and brimonidine on rabbit subconjunctival fibroblasts. J Glaucoma. 1999;8:72–6.CrossRefPubMed
3.
go back to reference Leng F, Liu P, Li H, Zhang J. Long-term topical antiglaucoma medications cause enhanced Tenon’s capsule fibroblast proliferation and abnormal TGF-β and MMP expressions: potential effects on glaucoma filtering surgery. Curr Eye Res. 2011;36:301–9.CrossRefPubMed Leng F, Liu P, Li H, Zhang J. Long-term topical antiglaucoma medications cause enhanced Tenon’s capsule fibroblast proliferation and abnormal TGF-β and MMP expressions: potential effects on glaucoma filtering surgery. Curr Eye Res. 2011;36:301–9.CrossRefPubMed
4.
go back to reference Walters TR. Development and use of brimonidine in treating acute and chronic elevations of intraocular pressure: a review of safety, efficacy, dose response, and dosing studies. Surv Ophthalmol. 1996;41 Suppl 1:S19–26.CrossRefPubMed Walters TR. Development and use of brimonidine in treating acute and chronic elevations of intraocular pressure: a review of safety, efficacy, dose response, and dosing studies. Surv Ophthalmol. 1996;41 Suppl 1:S19–26.CrossRefPubMed
5.
go back to reference Greenfield DS, Liebmann JM, Ritch R. Brimonidine: a new alpha2-adrenoreceptor agonist for glaucoma treatment. J Glaucoma. 1997;6:250–8.CrossRefPubMed Greenfield DS, Liebmann JM, Ritch R. Brimonidine: a new alpha2-adrenoreceptor agonist for glaucoma treatment. J Glaucoma. 1997;6:250–8.CrossRefPubMed
6.
go back to reference Fudemberg SJ, Batiste C, Katz LJ. Efficacy, safety, and current applications of brimonidine. Expert Opin Drug Saf. 2008;7:795–9.CrossRefPubMed Fudemberg SJ, Batiste C, Katz LJ. Efficacy, safety, and current applications of brimonidine. Expert Opin Drug Saf. 2008;7:795–9.CrossRefPubMed
7.
go back to reference Arthur S, Cantor LB. Update on the role of alpha-agonists in glaucoma management. Exp Eye Res. 2011;93:271–83.CrossRefPubMed Arthur S, Cantor LB. Update on the role of alpha-agonists in glaucoma management. Exp Eye Res. 2011;93:271–83.CrossRefPubMed
8.
go back to reference Walter KA, Gilbert DD. The adverse effect of perioperative brimonidine tartrate 0.2 % on flap adherence and enhancement rates in laser in situ keratomileusis patients. Ophthalmology. 2001;108:1434–8.CrossRefPubMed Walter KA, Gilbert DD. The adverse effect of perioperative brimonidine tartrate 0.2 % on flap adherence and enhancement rates in laser in situ keratomileusis patients. Ophthalmology. 2001;108:1434–8.CrossRefPubMed
9.
go back to reference Muñoz G, Albarrán-Diego C, Sakla HF, Javaloy J. Increased risk for flap dislocation with perioperative brimonidine use in femtosecond laser in situ keratomileusis. J Cataract Refract Surg. 2009;35:1338–42.CrossRefPubMed Muñoz G, Albarrán-Diego C, Sakla HF, Javaloy J. Increased risk for flap dislocation with perioperative brimonidine use in femtosecond laser in situ keratomileusis. J Cataract Refract Surg. 2009;35:1338–42.CrossRefPubMed
10.
go back to reference Nowroozzadeh MH. Early flap dislocation with perioperative brimonidine use in laser in situ keratomileusis. J Cataract Refract Surg. 2010;36:368.CrossRefPubMed Nowroozzadeh MH. Early flap dislocation with perioperative brimonidine use in laser in situ keratomileusis. J Cataract Refract Surg. 2010;36:368.CrossRefPubMed
11.
go back to reference Seong GJ, Hong S, Jung SA, Lee JJ, Lim E, Kim SJ, et al. TGF-beta-induced interleukin-6 participates in transdifferentiation of human Tenon’s fibroblasts to myofibroblasts. Mol Vis. 2009;15:2123–8.PubMedPubMedCentral Seong GJ, Hong S, Jung SA, Lee JJ, Lim E, Kim SJ, et al. TGF-beta-induced interleukin-6 participates in transdifferentiation of human Tenon’s fibroblasts to myofibroblasts. Mol Vis. 2009;15:2123–8.PubMedPubMedCentral
12.
go back to reference Hong S, Lee JB, Iizuka Y, Song YK, Seong GJ, Han SH. The role of focal adhesion kinase in the TGF-β-induced myofibroblast transdifferentiation of human Tenon’s fibroblasts. Korean J Ophthalmol. 2012;26:45–8.CrossRefPubMedPubMedCentral Hong S, Lee JB, Iizuka Y, Song YK, Seong GJ, Han SH. The role of focal adhesion kinase in the TGF-β-induced myofibroblast transdifferentiation of human Tenon’s fibroblasts. Korean J Ophthalmol. 2012;26:45–8.CrossRefPubMedPubMedCentral
13.
go back to reference Hong S, Park K, Kim JH, Han SH, Lee JB, Seong GJ. Role of heat shock protein 47 in transdifferentiation of human tenon’s fibroblasts to myofibroblasts. BMC Ophthalmol. 2012;12:49.CrossRefPubMedPubMedCentral Hong S, Park K, Kim JH, Han SH, Lee JB, Seong GJ. Role of heat shock protein 47 in transdifferentiation of human tenon’s fibroblasts to myofibroblasts. BMC Ophthalmol. 2012;12:49.CrossRefPubMedPubMedCentral
14.
go back to reference Mietz H, Esser JM, Welsandt G, Kociok N, Hueber A, Joussen A, et al. Latanoprost stimulates secretion of matrix metalloproteinases in tenon fibroblasts both in vitro and in vivo. Invest Ophthalmol Vis Sci. 2003;44:5182–8.CrossRefPubMed Mietz H, Esser JM, Welsandt G, Kociok N, Hueber A, Joussen A, et al. Latanoprost stimulates secretion of matrix metalloproteinases in tenon fibroblasts both in vitro and in vivo. Invest Ophthalmol Vis Sci. 2003;44:5182–8.CrossRefPubMed
15.
go back to reference Koh SW, Coll TJ, Rose L, Matsumoto Y, Higginbotham EJ. Antiglaucoma eye drop pulses-increased interleukin-6 secretion by Tenon’s capsule fibroblast cultures. J Glaucoma. 2004;13:200–9.CrossRefPubMed Koh SW, Coll TJ, Rose L, Matsumoto Y, Higginbotham EJ. Antiglaucoma eye drop pulses-increased interleukin-6 secretion by Tenon’s capsule fibroblast cultures. J Glaucoma. 2004;13:200–9.CrossRefPubMed
16.
go back to reference Ito T, Ohguro H, Mamiya K, Ohguro I, Nakazawa M. Effects of antiglaucoma drops on MMP and TIMP balance in conjunctival and subconjunctival tissue. Invest Ophthalmol Vis Sci. 2006;47:823–30.CrossRefPubMed Ito T, Ohguro H, Mamiya K, Ohguro I, Nakazawa M. Effects of antiglaucoma drops on MMP and TIMP balance in conjunctival and subconjunctival tissue. Invest Ophthalmol Vis Sci. 2006;47:823–30.CrossRefPubMed
17.
go back to reference Horn F, Henze C, Heidrich K. Interleukin-6 signal transduction and lymphocyte function. Immunobiology. 2000;202:151–67.CrossRefPubMed Horn F, Henze C, Heidrich K. Interleukin-6 signal transduction and lymphocyte function. Immunobiology. 2000;202:151–67.CrossRefPubMed
18.
go back to reference Rassler B, Marx G, Schierle K, Zimmer HG. Catecholamines can induce pulmonary remodeling in rats. Cell Physiol Biochem. 2012;30:1134–47.CrossRefPubMed Rassler B, Marx G, Schierle K, Zimmer HG. Catecholamines can induce pulmonary remodeling in rats. Cell Physiol Biochem. 2012;30:1134–47.CrossRefPubMed
Metadata
Title
Brimonidine reduces TGF-beta-induced extracellular matrix synthesis in human Tenon’s fibroblasts
Authors
Samin Hong
Sueng-Han Han
Chan Yun Kim
Kang Yoon Kim
Yoo Kyung Song
Gong Je Seong
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Ophthalmology / Issue 1/2015
Electronic ISSN: 1471-2415
DOI
https://doi.org/10.1186/s12886-015-0045-8

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