The Role of PAI-1 and TGF-β1 for Atopic Cataract Formation

Abstract

Purpose: : We previously showed Plasminogen Activator Inhibitor-1 (PAI-1), mRNA/protein expression in atopic cataracts. It was reported that PAI-1 expression is induced by, a profibrotic molecule, transforming growth factor (TGF)-β . Atopic cataract often accompany with abnormal transdifferentiation of lens epithelial cells (LEC) into myofibroblasts. In this study, we investigated the roles of PAI-1 for the pathogenesis of atopic cataracts with special reference to TGF-β.

Methods: : Real time PCR analysis was carried out to compare the TGF-β1 and TGF-β2 mRNA expression between the cDNA samples obtained during cataract surgeries from anterior capsules of atopic cataracts (n=7) and of senile cataracts (n=8). Immunohistochemical analysis was carried out with anti-α smooth muscle actin (SMA) and anti-PAI-1 antibodies using the anterior capsular tissues obtained from atopic cataracts during surgery. The lenses obtained from PAI-1 knockout (KO) mice and wild mice were incubated with recombinant (TGF)-β1 (50ng/ml). Cultured LEC were stimulated with TGF-β1, and PAI-1 and α-SMA expression by quantified by real time PCR.

Results: : The expression of TGF-β1 mRNA was significantly higher in the cDNA samples obtained from atopic cataracts compared to those from senile cataracts. PAI-1 immunostaining were localized around α-SMA positive myofibroblasts in fibrous tissues of atopic cataracts. The lenses obtained from PAI-1 KO mice were resistant for subcapsular cataract formation by TGF-β1 stimulation. PAI-1 and α-SMA mRNA expression was upregulated by 48hr-TGF-β1 stimulation.

Conclusions: : Our results suggested that PAI-1 and TGF-β1 synergistically play some roles for the pathophysiology of atopic cataracts.

Keywords: cataract • pathology: experimental