July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
The effect of VGF nerve growth factor inducible on retinal ganglion cell injury after optic nerve crush in mice
Author Affiliations & Notes
  • Masamitsu Shimazawa
    Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan
  • Hiroto Takeuchi
    Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan
  • Satoshi Inagaki
    Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan
    Department of Clinical Research, National Hospital Organization, Nagara Medical Center, Gifu, Japan
  • Wataru Morozumi
    Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan
  • Yukimichi Nakano
    Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan
  • Yuki Inoue
    Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan
  • Yoshiki Kuse
    Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan
  • Takahiro Mizoguchi
    Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan
  • Michinori Funato
    Department of Clinical Research, National Hospital Organization, Nagara Medical Center, Gifu, Japan
  • Hideo Kaneko
    Department of Clinical Research, National Hospital Organization, Nagara Medical Center, Gifu, Japan
  • Hideaki Hara
    Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan
  • Footnotes
    Commercial Relationships   Masamitsu Shimazawa, None; Hiroto Takeuchi, None; Satoshi Inagaki, None; Wataru Morozumi, None; Yukimichi Nakano, None; Yuki Inoue, None; Yoshiki Kuse, None; Takahiro Mizoguchi, None; Michinori Funato, None; Hideo Kaneko, None; Hideaki Hara, None
  • Footnotes
    Support  This study was supported in part by Grant-in-Aid for Scientific Research (C) (No. 17K11486) from the Ministry of Education, Culture, Sports, Science, and Technology, Japan and by Takeda Science Foundation,
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 6129. doi:
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      Masamitsu Shimazawa, Hiroto Takeuchi, Satoshi Inagaki, Wataru Morozumi, Yukimichi Nakano, Yuki Inoue, Yoshiki Kuse, Takahiro Mizoguchi, Michinori Funato, Hideo Kaneko, Hideaki Hara; The effect of VGF nerve growth factor inducible on retinal ganglion cell injury after optic nerve crush in mice. Invest. Ophthalmol. Vis. Sci. 2018;59(9):6129.

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

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Abstract

Purpose : VGF nerve growth factor inducible (VGF), a polypeptide upregulated by neurotrophic factors, facilitates neuronal survival, neurogenesis, neuronal activity and neuritis growth. The involvement of VGF for retinal ganglion cells (RGCs) survival is still unknown, although the Vgf mRNA expression has been identified in the adult mouse retina. Therefore, the purpose of this study was to elucidate VGF dynamics in the retina and the involvement in RGCs survival in the optic nerve crush (ONC) model used as an experimental glaucoma model.

Methods : The expression of the Vgf mRNA and the VGF protein after the ONC was determined by real-time PCR, and the site of VGF expression was determined by immunostaining. The effect of AQEE-30, a VGF peptide, for RGCs was evaluated by using in vivo ONC model and in vitro RGCs analysis. In ONC model, the number of fluorogold-labeled RGCs was evaluated by counting on the loss of RGCs. Moreover, the effect of AQEE-30 for in vitro RGCs was evaluated by Tuj1-positive neurite outgrowth on rat-derived primary cultured RGCs and human induced pluripotent stem cells (iPSCs)-derived RGCs-like cells.

Results : After the ONC, the Vgf mRNA and the VGF protein were increased in the retina. Immunostaining showed that the VGF was localized in glial cells including the Müller glia and astrocytes, but less in the retinal neurons and their axons. Intravitreal injection of AQEE-30 inhibited the loss of RGCs after the ONC, and it enhanced neurite outgrowth of rat primary RGCs and iPSCs-derived RGCs-like cells.

Conclusions : These findings indicate that VGF plays important roles in the survival and activity of RGCs. Therefore, VGF has the potential to be a novel therapeutic target for glaucoma.

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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