Tenascin-C promotes angiogenesis in fibrovascular membranes in eyes with proliferative diabetic retinopathy

Yoshiyuki Kobayashi, Shigeo Yoshida, Yedi Zhou, Takahito Nakama, Keijiro Ishikawa, Mitsuru Arima, Shintaro Nakao, Yukio Sassa, Atsunobu Takeda, Toshio Hisatomi, Yasuhiro Ikeda, Akira Matsuda, Koh Hei Sonoda, Tatsuro Ishibashi

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15 Citations (Scopus)

Abstract

Purpose: We previously demonstrated that tenascin-C was highly expressed in the fibrovascular membranes (FVMs) of patients with proliferative diabetic retinopathy (PDR). However, its role in the pathogenesis of FVMs has not been determined. The purpose of this study was to investigate what role tenascin-C plays in the formation and angiogenesis of FVMs. Methods: The level of tenascin-C was determined by sandwich enzyme-linked immunosorbent assay in the vitreous samples collected from patients with PDR and with a macular hole as control. The locations of tenascin-C, α- smooth muscle actin (SMA), CD34, glial fibrillary acidic protein (GFAP), and integrin αV in the FVMs from PDR patients were determined by immunohistochemistry. We also measured the in vitro expression of the mRNA and protein of tenascin-C in vascular smooth muscle cells (VSMCs) stimulated by interleukin (IL)-13. The effects of tenascin-C on cell proliferation, migration, and tube formation were determined in human retinal endothelial cells (HRECs) in culture. Results: The mean vitreous levels of tenascin-C were significantly higher in patients with PDR than in patients with a macular hole (p<0.001). Double immunofluorescence analyses of FVMs from PDR patients showed that tenascin-C co-stained FVMs with α-SMA, CD34, and integrin αV but not with GFAP. In addition, IL-13 treatment increased both the expression and secretion of tenascin-C by VSMCs in a dose-dependent manner. Tenascin-C exposure promoted proliferation, migration, and tube formation in HRECs. Tenascin-C neutralizing antibody significantly blocked the tube formation by HRECs exposed to VSMC-IL-13-conditioned medium. Conclusions: Our findings suggest that tenascin-C is secreted from VSMCs and promotes angiogenesis in the FVMs associated with PDR.

Original languageEnglish
Pages (from-to)436-445
Number of pages10
JournalMolecular vision
Volume22
Publication statusPublished - Apr 30 2016

All Science Journal Classification (ASJC) codes

  • Ophthalmology

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    Kobayashi, Y., Yoshida, S., Zhou, Y., Nakama, T., Ishikawa, K., Arima, M., Nakao, S., Sassa, Y., Takeda, A., Hisatomi, T., Ikeda, Y., Matsuda, A., Sonoda, K. H., & Ishibashi, T. (2016). Tenascin-C promotes angiogenesis in fibrovascular membranes in eyes with proliferative diabetic retinopathy. Molecular vision, 22, 436-445.