KMID : 0360220180590060549
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Journal of the Korean Ophthalmological Society 2018 Volume.59 No. 6 p.549 ~ p.555
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The Anti-fibrotic Effect of Nilotinib on Tenon¡¯s Capsule Fibroblasts in Vitro
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Kang Jeong-Woo
Jeong Jae-Hoon Moon Nam-Ju
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Abstract
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Purpose: To evaluate the anti-fibrotic effects of nilotinib on the survival of cultured human Tenon's capsule fibroblasts (HTFs).
Methods: HTF primary cultures were obtained from samples following glaucoma surgery. Primarily cultured HTFs were exposed to 1, 5, 10, and 20 ¥ìM nilotinib for 24 hours. The effects of nilotinib on HTF proliferation and cell viability were determined using the 3-(4,5-dimethylthiazone-2-yl)-2,5-diphenyl tetrazolium (MTT) assay, and apoptosis was determined by flow cytometry using annexin-V/propidium iodide (PI) double staining. Apoptosis-related proteins were detected by western blotting.
Results: The MTT assay showed that nilotinib induced an inhibition of HTF proliferation at concentrations of 10 and 20 ¥ìM (p < 0.001 and p < 0.001, respectively). Annexin V/PI double staining showed significantly increased apoptosis in cells treated with nilotinib. Nilotinib activated caspase-3, -9, and poly adenosine diphosphate ribose polymerase cleavage, and downregulated the expression of B-cell lymphoma-extra large and Bax, which indicated that nilotinib-induced apoptosis was partly mediated through the mitochondrial pathway. In addition, treatment with nilotinib decreased the expression of ¥á-smooth muscle actin and transforming growth factor-¥â.
Conclusions: Nilotinib decreased cell survival of cultured HTFs and induced mitochondria-mediated apoptosis. The results suggested that nilotinib may exert antiproliferative effects on HTFs, making it a possible agent to control postoperative fibrosis in patients undergoing glaucoma surgery.
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KEYWORD
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Fibrosis, Glaucoma surgery, Human Tenon¡¯s capsule fibroblast, Nilotinib
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