title: The prostaglandin f2α analog fluprostenol attenuates the fibrotic effects of connective tissue growth factor on human trabecular meshwork cells.
abstract: Abstract Purpose: The trabecular meshwork (TM) outflow pathways of the aqueous humor show an increase in extracellular matrix in patients with primary open-angle glaucoma (POAG). The increase in TM extracellular matrix appears to be caused by transforming growth factor-β signaling and its downstream mediator connective-tissue growth factor (CTGF). Here we studied whether treatment with the prostaglandin F2α analog fluprostenol modulates the CTGF-mediated increase of the TM extracellular matrix.
  
  
  METHODS
  Human TM cells from 3 different donors were treated with CTGF (50 ng/mL) and/or fluprostenol (10(-6) M and 10(-7) M) and were analyzed by real-time reverse transcription polymerase chain reaction and Western blotting. Cell supernatants of the treated cells were analyzed by zymography.
  
  
  RESULTS
  Treatment with CTGF induced the expression and synthesis of CTGF, fibronectin, collagen type IV and VI, while treatment with fluprostenol alone had no effects. The effects of CTGF were blocked by 1-h pretreatment with fluprostenol in a dose-dependent manner. Treatment with fluprostenol or combined fluprostenol/CTGF induced the activity of matrix metalloproteinase 2 (MMP2) in TM cells, whereas treatment with CTGF alone had no effects on MMP2 activity.
  
  
  CONCLUSIONS
  Fluprostenol blocks the fibrotic effects of CTGF on human TM cells and increases the activity of MMP2. Both effects have the distinct potential to attenuate a CTGF-mediated increase in TM extracellular matrix in patients with POAG and any effects on TM outflow resistance that may result from that.
authors.affiliation: Institute of Human Anatomy and Embryology, University of Regensburg , Regensburg, Germany .
authors.forename: Rudolf
authors.initials: R
authors.lastname: Fuchshofer
authors.forename: Sabrina
authors.initials: S
authors.lastname: Kuespert
authors.forename: Benjamin
authors.initials: B
authors.lastname: Junglas
authors.forename: Ernst R
authors.initials: ER
authors.lastname: Tamm
mesh_terms: D000328:Adult; D000368:Aged; D001082:Aqueous Humor / Q000378:metabolism; D015153:Blotting, Western; D002478:Cells, Cultured; D055513:Connective Tissue Growth Factor / Q000008:administration & dosage* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005109:Extracellular Matrix / Q000187:drug effects / Q000473:pathology; D005902:Glaucoma, Open-Angle / Q000503:physiopathology; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects* / Q000378:metabolism; D008875:Middle Aged; D011461:Prostaglandins F, Synthetic / Q000008:administration & dosage / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D014129:Trabecular Meshwork / Q000166:cytology / Q000187:drug effects* / Q000473:pathology
chemical_list: D011461:Prostaglandins F, Synthetic; D055513:Connective Tissue Growth Factor; C006326:fluprostenol; D020778:Matrix Metalloproteinase 2