title: Brimonidine reduces TGF-beta-induced extracellular matrix synthesis in human Tenon's fibroblasts.
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.
authors.affiliation: Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea.
authors.forename: Samin
authors.initials: S
authors.lastname: Hong
authors.affiliation: Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea.
authors.forename: Sueng-Han
authors.initials: SH
authors.lastname: Han
authors.affiliation: Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea.
authors.forename: Chan Yun
authors.initials: CY
authors.lastname: Kim
authors.affiliation: Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea.
authors.forename: Kang Yoon
authors.initials: KY
authors.lastname: Kim
authors.affiliation: Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea.
authors.forename: Yoo Kyung
authors.initials: YK
authors.lastname: Song
authors.affiliation: Institute of Vision Research, Department of Ophthalmology, Yonsei University College of Medicine, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, Republic of Korea. gjseong@yuhs.ac.
authors.forename: Gong Je
authors.initials: GJ
authors.lastname: Seong
mesh_terms: D000199:Actins / Q000378:metabolism; D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology*; D015153:Blotting, Western; D000068438:Brimonidine Tartrate / Q000494:pharmacology*; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D024061:Collagen Type III / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005353:Fibronectins; D005355:Fibrosis; D006801:Humans; D058475:Tenon Capsule / Q000166:cytology*; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
chemical_list: D000199:Actins; D058647:Adrenergic alpha-2 Receptor Agonists; D024042:Collagen Type I; D024061:Collagen Type III; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D053773:Transforming Growth Factor beta1; D000068438:Brimonidine Tartrate