Purpose The purpose of this study was to evaluate the effect of aldose reductase (AR) inhibition on Posterior capsular opacification (PCO) using pig eye capsular bag model. Methods Pig eye capsular bags were prepared by capsulorhexis and cultured in medium without or with AR inhibitors for 7 days. Immunostaining was performed in paraformaldehyde-fixed capsular bags to determine the expression of proliferating cell nuclear antigen (PCNA), α-smooth muscle actin (SMA), β-crystallin, and intercellular adhesion molecule (ICAM)-1. We examined the effect of AR inhibition on basic fibroblast growth factor (b-FGF) -induced mitogenic signaling in cultured human lens epithelial cells (HLEC). Cell growth was assessed by MTT assay and cell counting, the expression of α-SMA, β-crystallin and ICAM-1 by Western Blot and immunocytochemical analysis, protein kinases by Western blot analysis, and NF-κB activation by Gel shift and reporter assays. Results During culture of pig eye capsular bags, residual cells on both the anterior and posterior capsule showed vigorous growth. Treatment with AR inhibitors significantly prevented the lens epithelial cell growth in capsular bags and expression of α-SMA, β-crystallin and ICAM-1. HLEC showed a dose-dependent response to b-FGF, proliferation at lower (<20 ng/ml) and differentiation/transdifferentiation at higher (>50 ng/ml) concentrations. Inhibition of AR also prevented the b-FGF -induced activation of ERK1/2, JNK and NF-κB in HLEC. Conclusions Our results suggest that AR is required for lens epithelial cell growth and differentiation/transdifferentiation in the capsular bags indicating that inhibition of AR could be a potential therapeutic target in the prevention of PCO.
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