July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Inhibitional effect of TGF-β2-induced EMT in RPE cells by an RAR-γ agonist
Author Affiliations & Notes
  • Yuka Kobayashi
    Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan
  • Tomoko Orita
    Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan
  • Chiemi Yamashiro
    Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan
  • Syohei Uchi
    Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan
  • Makoto Hatano
    Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan
  • Masaaki Kobayashi
    Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan
  • Kazuhiro Tokuda
    Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan
  • Ryoji Yanai
    Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan
  • Atsunobu Takeda
    Kyushu University School of Medicine, Hukuoka, Japan
  • Tatsuro Ishibashi
    Kyushu University School of Medicine, Hukuoka, Japan
  • Koh-hei Sonoda
    Kyushu University School of Medicine, Hukuoka, Japan
  • Kazuhiro Kimura
    Yamaguchi University School of Medicine, Ube, Yamaguchi, Japan
  • Footnotes
    Commercial Relationships   Yuka Kobayashi, None; Tomoko Orita, None; Chiemi Yamashiro, None; Syohei Uchi, None; Makoto Hatano, None; Masaaki Kobayashi, None; Kazuhiro Tokuda, None; Ryoji Yanai, None; Atsunobu Takeda, None; Tatsuro Ishibashi, None; Koh-hei Sonoda, None; Kazuhiro Kimura, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 4003. doi:
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      Yuka Kobayashi, Tomoko Orita, Chiemi Yamashiro, Syohei Uchi, Makoto Hatano, Masaaki Kobayashi, Kazuhiro Tokuda, Ryoji Yanai, Atsunobu Takeda, Tatsuro Ishibashi, Koh-hei Sonoda, Kazuhiro Kimura; Inhibitional effect of TGF-β2-induced EMT in RPE cells by an RAR-γ agonist. Invest. Ophthalmol. Vis. Sci. 2018;59(9):4003.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : The fibrotic reaction mediated by retinal pigment epithelial (RPE) cells contributes to the loss of vision associated with age-related macular degeneration (AMD). We examined the role of retinoic acid receptor-γ (RAR-γ) in the epithelial-mesenchymal transition (EMT) and other processes of fibrosis in mouse retinal pigment epithelium (RPE) cells and subretinal fibrosis mouse model.

Methods : Primary mouse RPE cells cultured in a type I collagen gel were incubated with or without transforming growth factor-β2 (TGF-β2) and the RAR-γ agonist R667. Collagen gel contraction was determined by measurement of gel diameter. Expression of α–smooth muscle actin (α-SMA), mitogen-activated protein kinases, Smad2, matrix metalloproteinases (MMPs) was examined by immunoblot analysis. Fibronectin and interleukin-6 (IL-6) secretion was measured with immunoassays. Immunohistofluorescence analysis with antibodies to glial fibrillary acidic protein and type I collagen was performed with subretinal fibrosis mouse model in vivo.

Results : The RAR-γ agonist R667 inhibited TGF-β2-induced collagen gel contraction mediated by the RPE cells in a concentration- and time-dependent manner. Expression of the mesenchymal markers α-SMA and fibronectin, the release of IL-6, and mitogen-activated protein kinases, and Smad2, induced by TGF-β2 were inhibited by R667. TGF-β2–induced release of MMP-2, MMP-3, MMP-8, and MMP-9 from RPE cells was also suppressed by the RAR-γ agonist. Immunohistofluorescence analysis with antibodies to glial fibrillary acidic protein and type I collagen showed that R667 inhibited the development of subretinal fibrosis in a mouse model in vivo.

Conclusions : Our observations suggest that RAR-γ signaling may play a key role in the pathogenesis of subretinal fibrosis associated with AMD.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

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