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Kanji Hori, Akira Matsuda, Nobuyuki Ebihara, Kojiro Imai, Kazuhiko Mori, Toshinari Funaki, Yasuo Watanabe, Satoru Nakatani, Kiyotaka Okada, Osamu Matsuo, Akira Murakami; Involvement of Plasminogen Activator Inhibitor-1 in the Pathogenesis of Atopic Cataracts. Invest. Ophthalmol. Vis. Sci. 2012;53(4):1846-1851. doi: 10.1167/iovs.11-8380.
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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.
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.
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.
The findings of this study suggest that the IFN-γ, PAI-1, and TGF-β1 are involved in the pathophysiology of atopic cataracts.
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