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K Krishna Sharma, Leike Xie, Puttur Santhoshkumar, Lixing Reneker; Histone Deacetylase Inhibitors Trichostatin A and Vorinostat Inhibit TGF-β2 -Induced Epithelial to Mesenchymal Cell Transition of Lens Epithelium. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2953.
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To investigate the effects of histone deacetylase inhibitors, Trichostatin A (TSA) and Vorinostat (suberoylanilide hydroxamic acid, SAHA) on pig and human lens epithelial explants treated with TGF-β2
Lens capsules were isolated from fresh pig eyes and secured in serum-free DMEM medium on 60 mm dishes at 37°C 5% CO2 for 12 hours. Tissues were then incubated in serum-free DMEM containing TGF-β2 (5 ng/ml) with or without TSA (0.25, 0.5 and 1 µM) or SAHA (1.2, 2.5 and 5 µM) for up to three days. Western blotting (WB), immunocytochemistry (ICC) and wound healing assay were performed to determine the effect of inhibitors in lens epithelia.
Both WB and ICC showed that α-SMA was highly expressed in lens epithelial cells treated with TGF-β2, compared to the non-treated control. The α-SMA expression was inhibited by both histone deacetylase inhibitors dose-dependently, with the complete inhibition in 0.5 µM TSA or 2.5 µM SAHA. Wound healing assay showed that TGF-β2 stimulated the epithelial cell proliferation and migration and it was prevented by 0.5µM TSA or 2.5µM SAHA.
Trichostatin A and Vorinostat dose-dependently inhibited TGF-β2-induced lens epithelial cell transition to myofibroblast and proliferation and migration in cultured pig lens capsule. These results suggest that HDACIs have the potential to prevent PCO and fibrosis after cataract surgery.
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