title: Connective tissue growth factor is increased in pseudoexfoliation glaucoma.
abstract: OBJECTIVE
  Pseudoexfoliation (PXF) syndrome is a generalized disorder of the extracellular matrix (ECM) involving the trabecular meshwork (TM), associated with raised intraocular pressure, glaucoma, and cataract. The purposes of this study were to quantify aqueous humor connective tissue growth factor (CTGF) in PXF glaucoma, to determine the effect of CTGF on ECM production in TM cells, and to identify intracellular CTGF signaling pathways.
  
  
  METHODS
  Aqueous humor samples were obtained from patients undergoing routine cataract surgery or trabeculectomy. CTGF levels were quantified by ELISA. The effect of CTGF on fibrillin-1 expression in TM cells was investigated by real-time PCR. Western immunoblot analysis was used to investigate CTGF signaling. c-Jun/AP-1 activation was measured in CHO cells by ELISA after stimulation with CTGF.
  
  
  RESULTS
  PXF with glaucoma had the highest aqueous humor level of CTGF (n = 18; 5.15 ± 0.79 ng/mL [SEM]; P < 0.01) compared with PXF without glaucoma (n = 15; 2.76 ± 0.64 ng/mL), primary open-angle glaucoma (POAG; n = 20; 3.05 ± 0.40 ng/mL), and the control (n = 21; 2.60 ± 0.29 ng/mL). In vitro exposure of TM cells to CTGF resulted in a 50% upregulation of fibrillin-1, which was partially blocked with the MEK (mitogen-activated protein extracellular kinase) inhibitor PD098059. Western blot analysis demonstrated increased phosphorylation of p42/44 MAPK, p38 MAPK, and the JNK pathways in response to CTGF. c-Jun/AP-1 activity was significantly increased in response to CTGF treatment.
  
  
  CONCLUSIONS
  Increased levels of CTGF in the aqueous humor of PXF patients likely has pathologic significance through increased production of fibrillin-1 by TM cells through activation of p42/44 MAPK, p38 MAPK, and JNK pathways.
authors.affiliation: School of Medicine and Medical Science, UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland.
authors.forename: John G
authors.initials: JG
authors.lastname: Browne
authors.forename: Su Ling
authors.initials: SL
authors.lastname: Ho
authors.forename: Rosemary
authors.initials: R
authors.lastname: Kane
authors.forename: Noelynn
authors.initials: N
authors.lastname: Oliver
authors.forename: Abbot F
authors.initials: AF
authors.lastname: Clark
authors.forename: Colm J
authors.initials: CJ
authors.lastname: O'Brien
authors.forename: John K
authors.initials: JK
authors.lastname: Crean
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001082:Aqueous Humor / Q000378:metabolism*; D015153:Blotting, Western; D002387:Cataract Extraction; D002478:Cells, Cultured; D055513:Connective Tissue Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D017889:Exfoliation Syndrome / Q000378:metabolism* / Q000601:surgery; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D000071838:Fibrillin-1; D000071837:Fibrillins; D005902:Glaucoma, Open-Angle / Q000378:metabolism* / Q000601:surgery; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014129:Trabecular Meshwork / Q000187:drug effects / Q000378:metabolism; D014130:Trabeculectomy; D014157:Transcription Factors / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D054392:Adipokines
chemical_list: D055513:Connective Tissue Growth Factor; D000071838:Fibrillin-1; D000071837:Fibrillins; D048670:MAP Kinase Kinase 4; D008840:Microfilament Proteins; D019950:Mitogen-Activated Protein Kinase 1; D012333:RNA, Messenger; D014157:Transcription Factors; D048051:p38 Mitogen-Activated Protein Kinases; C000605722:FBN1 protein, human; D054392:Adipokines; C478359:WDR77 protein, human