title: Involvement of plasminogen activator inhibitor-1 in the pathogenesis of atopic cataracts.
abstract: OBJECTIVE
  Further to our previous report of a genetic association between interferon-gamma (IFN-γ) receptor 1 gene and atopic cataract, we investigated the roles of plasminogen activator inhibitor-1 (PAI-1), a fibrosis-related, IFN-γ downstream molecule, in the pathogenesis of atopic cataracts.
  
  
  METHODS
  Cultured lens epithelial cells (LECs) were stimulated by IFN-γ and quantified by PAI-1 mRNA/protein expression. PAI-1 and TGF-β mRNA expression was quantified using cDNA samples obtained from the lens epithelium of atopic cataract patients (n = 7) and of senile cataract patients (n = 8). The anterior capsules obtained from atopic cataracts (n = 9) were immunostained with anti-PAI-1 and anti-alpha smooth muscle actin (α-SMA) antibodies. PAI-1 gene expression was knocked down by PAI-1 siRNA, and α-SMA expression was examined under TGF-β1 stimulation. Expression of α-SMA was examined as a pathological hallmark of anterior subcapsular cataracts, commonly observed in atopic cataracts.
  
  
  RESULTS
  The IFN-γ stimulation induced PAI-1 mRNA/protein expression in the LECs from 24 to 48 hours after stimulation. The expression of PAI-1 mRNA and TGF-β1 mRNA was significantly higher in the cDNA samples obtained from the atopic cataracts than those obtained from the senile cataracts. PAI-1-positive immunostaining was observed at the fibrotic lesion of the atopic cataracts, and α-SMA-positive myofibroblasts were observed at the vicinity of the PAI-1-positive lesion in all nine samples examined. PAI-1 gene knockdown resulted in reduced α-SMA expression in the LECs.
  
  
  CONCLUSIONS
  The findings of this study suggest that the IFN-γ, PAI-1, and TGF-β1 are involved in the pathophysiology of atopic cataracts.
authors.affiliation: Department of Ophthalmology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Kanji
authors.initials: K
authors.lastname: Hori
authors.forename: Akira
authors.initials: A
authors.lastname: Matsuda
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Ebihara
authors.forename: Kojiro
authors.initials: K
authors.lastname: Imai
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Mori
authors.forename: Toshinari
authors.initials: T
authors.lastname: Funaki
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Satoru
authors.initials: S
authors.lastname: Nakatani
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Okada
authors.forename: Osamu
authors.initials: O
authors.lastname: Matsuo
authors.forename: Akira
authors.initials: A
authors.lastname: Murakami
mesh_terms: D015153:Blotting, Western; D002386:Cataract / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000494:pharmacology; D007908:Lens, Crystalline / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008854:Microscopy, Electron; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis / Q000235:genetics
chemical_list: D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D007371:Interferon-gamma