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J. Oh, J. Tae, T. Park, Y. Moon, H. Chin; Inhibitory Effects of Imatinib Mesylate (Gleevec®) on the Transdifferentiation of Lens Epithelial Cells into Fibroblast in Capsular Bag Model . Invest. Ophthalmol. Vis. Sci. 2004;45(13):372.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: In after–cataract, the lens epithelial cells(LECs) transdifferentiated into the fibroblast on the posterior capsule. Imatinib mesylate(IM) is a tyrosine kinase inhibitor that targets the BCR–ABL protein in chronic myeloid leukemia. This study was to investigate whether IM would inhibit the transdifferentiation of lens epithelial cells into fibroblasts using capsular bag model which LECs were cultured directly on the posterior capsule. Methods: LECs were cultured in capsular bag model with IM at concentration of 10, 20, 30 µM(Group I), TGF–ß at 1, 10 ng/ml(Group II), the combination of the same concentration of TGF–ß and IM (Group III). At day 7 of culture, the effect of IM and TGF–ß on the transdifferentation of lens epithelial cells into fibroblasts was observed using phase contrast microscopy, immunohistochemistry on the expression of α–SMA, western blot analysis and BrdU immunohistochemistry. To determine the optimal inhibitory concentration of IM for clinical application, we examined the corneal thickness after anterior chamber perfusion as same exposure time and concentration of IM. Results: According to the observation using a phase contrast microscope, IM treated group showed a smaller number of fibroblast and the area was decreased by treatment of IM in dose dependant manner and TGF–ß treated group showed a large number of fibroblast. In α–SMA immunohistochemistry, positive cell counts for α–SMA were decreased in group I and III, but increased in group II . The western blot analysis revealed the inhibiting effects of IM on transdifferentiation. BrdU incorporation in the nucleus of proliferating cells showed in the same pattern of α–SMA expression. The increase of concentration of TGF–ß gave rised to acceleration of transdifferentiation. No significant corneal edema was noted after anterior chamber irrigation with IM. Conclusions: Thus, application with 30 µM IM for 3 min during cataract surgery would be effective in inhibiting the transdifferentiation of lens epithelial cells into fibroblasts for the prevention of after–cataract, while not resulting in corneal toxicity.
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