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Yoshiyuki Kobayashi, Shigeo Yoshida, Yuki Kubo, Yedi Zhou, Takahito Nakama, Keijiro Ishikawa, Shintaro Nakao, Yuji Oshima, Akira Matsuda, Tatsuro Ishibashi, Koh-hei Sonoda; Inhibition of choroidal neovascularization by siRNA targeting tenascin-C. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4435.
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© ARVO (1962-2015); The Authors (2016-present)
Tenascin-C has been reported to be highly expressed in choroidal neovascular membranes (CNVMs) from patients with age-related macular degeneration (AMD). However, its exact roles of tenascin-C in the pathogenesis of CNVMs remain elusive. The purpose of this study was to investigate the role of tenascin-C in CNVM formation and to confirm the suppressive effect of tenascin-C siRNA on mouse CNV model.
CNVMs of AMD patients and mouse CNV models were examined immunohistochemically for the expression of tenascin-C, α-SMA, pan-cytokeratin, CD31, and CD34. Tenascin-C mRNA levels in human RPE cells treated with or without TGF-β2 (0, 1, 3, and 10ng/mL) were examined by real-time PCR. Proliferation of human microvascular endothelial cells (HMVECs) treated with tenascin-C was measured using bromodeoxyu-ridine (BrdU)-ELISA. CNV volumes of tenascin-C knock-out mice and wild type mice treated with vitreous injections of tenascin-C siRNA were measured using isolectin-B4 staining.
Double immunofluorescence analyses showed that tenascin-C was co-stained with fibroblast-like RPE cells and vascular endothelial cells in human CNVMs and mouse CNV. TGF-β2 induced tenascin-C mRNA expression in RPE cells. Tenascin-C siRNA almost completely suppressed the TGFβ2-induced tenascin-C expression. Tenascin-C promoted the proliferation of HMVECs. In mouse CNV model, the mean CNV volume was significantly smaller in tenascin-C knock-out group and tenascin-C siRNA injection group compared with the control group.
Tenascin-C produced by RPE cells may play a role in promoting CNV. siRNA targeting tenascin-C may have therapeutic potential for inhibiting CNV.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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