Involvement of plasminogen activator inhibitor-1 in the pathogenesis of atopic cataracts

Invest Ophthalmol Vis Sci. 2012 Apr 6;53(4):1846-51. doi: 10.1167/iovs.11-8380.


Purpose: 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cataract / genetics*
  • Cataract / metabolism
  • Cataract / pathology
  • Cells, Cultured
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Epithelial Cells / ultrastructure
  • Gene Expression Regulation*
  • Humans
  • Immunohistochemistry
  • Interferon-gamma / pharmacology
  • Lens, Crystalline / drug effects
  • Lens, Crystalline / metabolism*
  • Lens, Crystalline / pathology
  • Microscopy, Electron
  • Plasminogen Activator Inhibitor 1 / biosynthesis
  • Plasminogen Activator Inhibitor 1 / genetics
  • RNA, Messenger / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transforming Growth Factor beta1 / biosynthesis
  • Transforming Growth Factor beta1 / genetics


  • Plasminogen Activator Inhibitor 1
  • RNA, Messenger
  • Transforming Growth Factor beta1
  • Interferon-gamma