July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
The oligodendrocyte derived from familial glaucoma patients-iPSCs decreases neuroprotective action for retinal ganglion cells
Author Affiliations & Notes
  • Satoshi Inagaki
    Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan, Gifu, Japan
    Department of Clinical Research, National Hospital Organization, Nagara Medical Center, Gifu, Japan
  • Kazuhide Kawase
    Department of Ophthalmology, Gifu University Graduate School of Medicine, Gifu, Japan
  • Michinori Funato
    Department of Clinical Research, National Hospital Organization, Nagara Medical Center, Gifu, Japan
  • Kazuki Ohuchi
    Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan, Gifu, Japan
    Department of Clinical Research, National Hospital Organization, Nagara Medical Center, Gifu, Japan
  • Shiori Ando
    Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan, Gifu, Japan
    Department of Clinical Research, National Hospital Organization, Nagara Medical Center, Gifu, Japan
  • Arisu Sato
    Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan, 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, Gifu, Japan
  • Masamitsu Shimazawa
    Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan, Gifu, Japan
  • Daisuke Iejima
    Division of Molecular and Cellular Biology, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan
  • Takeshi Iwata
    Division of Molecular and Cellular Biology, National Institute of Sensory Organs, National Hospital Organization Tokyo Medical Center, Tokyo, Japan
  • Tetsuya Yamamoto
    Department of Ophthalmology, Gifu University Graduate School of Medicine, 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, Gifu, Japan
  • Footnotes
    Commercial Relationships   Satoshi Inagaki, None; Kazuhide Kawase, None; Michinori Funato, None; Kazuki Ohuchi, None; Shiori Ando, None; Arisu Sato, None; Wataru Morozumi, None; Masamitsu Shimazawa, None; Daisuke Iejima, None; Takeshi Iwata, None; Tetsuya Yamamoto, None; Hideo Kaneko, None; Hideaki Hara, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 3751. doi:
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    • Get Citation

      Satoshi Inagaki, Kazuhide Kawase, Michinori Funato, Kazuki Ohuchi, Shiori Ando, Arisu Sato, Wataru Morozumi, Masamitsu Shimazawa, Daisuke Iejima, Takeshi Iwata, Tetsuya Yamamoto, Hideo Kaneko, Hideaki Hara; The oligodendrocyte derived from familial glaucoma patients-iPSCs decreases neuroprotective action for retinal ganglion cells. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3751.

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

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Abstract

Purpose : Glaucoma is characterized by a progressive loss of retinal ganglion cells (RGCs) with axonal degeneration, suggesting that axonal degeneration precede RGCs death. Structurally, RGCs axons are surrounded by oligodendrocytes (OLs). Therefore, our purpose is to elucidate whether OLs would contribute to axonal degeneration and RGCs death using patient RGCs or OLs culture system using induced pluripotent stem cells (iPSCs) derived from patients who have E50K-optineurin mutation.

Methods : OLs and RGCs were generated from iPSCs derived two healthy patient indivisuals (WT-iPSCs; 201B6 and 201B7 Cell line) and three patients with OPTNE50K-NTG (E50K-iPSCs). The phenotype of WT-iPSCs OLs and E50K-iPSCs OLs was compared by using Western blotting for LC3B, p62, cleaved caspase-3, myelin basic protein (MBP) and nuclear factor-kappaB (NF-κB). In immunostaining analysis, O4 was used as oligodendrocyte precursor cells (OPCs) marker and MBP as mature OLs marker.

Results : MBP-positive mature OLs were produced from iPSCs. Comparing with WT-iPSCs OLs, E50K-iPSCs OLs showed prompting autophagic flux, increased cleaved caspase-3, enhanced MBP insolubility and decreasing MBP-positive area. Moreover, conditioned medium (CM) collected from E50K-iPSCs OLs culture decreased ATH5/TUJ1-positive cells and neurite outgrowth comparing with those of CM collected from WT-iPSCs OLs

Conclusions : Our study demonstrated that E50K-iPSCs OLs showed promoting autophagic flux, abnormal features of MBP protein and increasing cleaved caspase-3, suggesting that E50K-iPSCs OLs itself might enhance vulnerability. Moreover, although secreted soluble factor from WT-iPSCs OLs showed neuroprotective action for WT and E50K-iPSCs RGCs, E50K-iPSCs OLs showed weaker neuroprotective action than WT-iPSCs OLs.

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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