September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Inhibition of choroidal neovascularization by siRNA targeting tenascin-C
Author Affiliations & Notes
  • Yoshiyuki Kobayashi
    Ophthalmology, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
  • Shigeo Yoshida
    Ophthalmology, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
  • Yuki Kubo
    Ophthalmology, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
  • Yedi Zhou
    Ophthalmology, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
  • Takahito Nakama
    Ophthalmology, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
  • Keijiro Ishikawa
    Ophthalmology, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
  • Shintaro Nakao
    Ophthalmology, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
  • Yuji Oshima
    Ophthalmology, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
  • Akira Matsuda
    Ophthalmology, Juntendo University, Bunkyo-ku, Japan
  • Tatsuro Ishibashi
    Ophthalmology, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
  • Koh-hei Sonoda
    Ophthalmology, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan
  • Footnotes
    Commercial Relationships   Yoshiyuki Kobayashi, None; Shigeo Yoshida, None; Yuki Kubo, None; Yedi Zhou, None; Takahito Nakama, None; Keijiro Ishikawa, None; Shintaro Nakao, None; Yuji Oshima, None; Akira Matsuda, None; Tatsuro Ishibashi, None; Koh-hei Sonoda, None
  • Footnotes
    Support  Grant-in-Aid for JSPS Fellows from Japan Society for the Promotion of Science (No.15J03433)
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 4435. doi:
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    • Get Citation

      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)

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Abstract

Purpose : 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.

Methods : 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.

Results : 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.

Conclusions : 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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