title: 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.
abstract: OBJECTIVE
  To investigate the changes in Tenon's capsule fibroblast (HTF) proliferation and their expressions of transforming growth factor-β (TGF-β) and matrix metalloproteinases (MMPs) in patients with long-term use of topical antiglaucoma medications, and to evaluate the potential effect of these medications on the outcome of glaucoma filtering surgery for primary open-angle glaucoma (POAG).
  
  
  METHODS
  HTFs isolated from the conjunctiva of ten POAG patients and ten control patients with cataract or retinal detachment were tested for their in vitro proliferation capacity. RT-PCR (reverse-transcription polymerase chain reaction) was performed to detect the expressions of TGF-β and MMP mRNAs in the HTFs, and the expression of TGF-β2 protein was detected immunohistochemically. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression of TGF-β1 in the supernatant of the HTFs treated with the topical antiglaucoma agents.
  
  
  RESULTS
  The HTFs from the POAG patients showed significantly higher proliferative activity than those from the control patients (P = 0.0013). The HTFs in the POAG group showed significantly higher expressions of TGF-β2 and TGF-β3 mRNA and lower MMP-9 mRNA than the control HTFs. MMP-3 mRNA was not detected in the HTFs in POAG groups, but lowly expressed in the control HTFs. The HTFs in the POAG group had a significantly higher expression of TGF-β2 protein; TGF-β1 protein was not detected in the control HTFs, but was highly expressed in the POAG group. Treatment of the HTFs with latanoprost resulted in a 4-fold increase in TGF-β1 expression in both groups, which was comparable for the expression after the exposure.
  
  
  CONCLUSIONS
  Long-term use of some topical antiglaucoma medications might be associated with enhanced HTF proliferation and abnormal expressions of TGF-β and MMPs, which might have promoted scarring of the filtering blebs following glaucoma filtering surgery.
authors.affiliation: Department of Ophthalmology, First Affiliated Hospital, Harbin Medical University, Harbin, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Leng
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.forename: Hulun
authors.initials: H
authors.lastname: Li
authors.forename: Jiaying
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000287:Administration, Topical; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D003228:Conjunctiva / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D018463:Filtering Surgery; D005500:Follow-Up Studies; D005902:Glaucoma, Open-Angle / Q000188:drug therapy*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D020782:Matrix Metalloproteinases / Q000235:genetics*; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D058475:Tenon Capsule / Q000378:metabolism / Q000473:pathology*; D016212:Transforming Growth Factor beta / Q000235:genetics*
chemical_list: D000959:Antihypertensive Agents; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D020782:Matrix Metalloproteinases