Prevention of posterior capsular opacification through aldose reductase inhibition.

Umesh C S Yadav, Farshid Ighani-Hosseinabad, Frederik J G M van Kuijk, Satish K Srivastava, Kota V Ramana

Index: Invest. Ophthalmol. Vis. Sci. 50(2) , 752-9, (2009)

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Abstract

The purpose of this study was to evaluate the effect of aldose reductase (AR) inhibition on posterior capsular opacification (PCO) with the use of a pig eye capsular bag model.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), alpha-smooth muscle actin (SMA), beta-crystallin, and intercellular adhesion molecule (ICAM)-1. The effect of AR inhibition on basic fibroblast growth factor (BFGF)-induced mitogenic signaling in cultured human lens epithelial cells (HLECs) was examined. Cell growth was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and cell counting, the expression of alpha-SMA, beta-crystallin, and ICAM-1 by Western blot and immunocytochemical analysis, protein kinases by Western blot analysis, and NF-kappaB activation by gel shift and reporter assays.During culture of pig eye capsular bags, residual cells on both the anterior and the posterior capsule showed vigorous growth. Treatment with AR inhibitors significantly prevented the lens epithelial cell growth in capsular bags and expression of alpha-SMA, beta-crystallin, and ICAM-1. HLECs showed a dose-dependent response to BFGF, proliferation at lower concentrations (<20 ng/mL) and differentiation/transdifferentiation at higher concentrations (>50 ng/mL). Inhibition of AR also prevented the BFGF-induced activation of ERK1/2, JNK, and NF-kappaB in HLECs.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.