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Pathological analysis using iPSCs derived from autosomal dominant optic neuropathy patients

Research Project

Project/Area Number 19K18829
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 56060:Ophthalmology-related
Research InstitutionTohoku University

Principal Investigator

Kobayashi Wataru  東北大学, 医学系研究科, 助教 (20646442)

Project Period (FY) 2019-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
KeywordsヒトiPS細胞 / 網膜神経節細胞 / 視神経委縮 / 常染色体優性視神経萎縮症 / ミトコンドリア / iPS細胞 / 神経突起 / 視神経萎縮
Outline of Research at the Start

本研究では、Optic atrophy 1 (OPA1) 遺伝子変異による遺伝性視神経症である常染色体優性視神経萎縮症(autosomal dominant optic atrophy: ADOA) 患者からinduced pluripotent stem (iPS) 細胞を作製し、立体網膜組織に分化誘導を行う。作製した立体網膜組織から網膜神経節細胞を単離し、網膜神経節細胞及びその軸索である視神経におけるOPA1遺伝子変異の影響を細胞分子生物学的手法で解析する。

Outline of Final Research Achievements

We established iPSCs from the skin of a patient with autosomal dominant optic atrophy (ADOA) who had an OPA1 mutation. The iPSCs were induced to differentiate into artificial three-dimensional retinal organoids using a differentiation induction method with minor modifications to a previous report. Immunostaining for Pou4f2, a retinal ganglion cell marker, was performed in the 3D retinal organoids on the 40th day of differentiation, and there was no significant difference in the number of Pou4F2-positive cells between the ADOA group and the normal group. The number of mitochondria in the neurites of isolated retinal ganglion cells was significantly decreased in the ADOA group. It is likely that abnormal mitochondrial function is responsible for neural atrophy.

Translated with www.DeepL.com/Translator (free version)

Academic Significance and Societal Importance of the Research Achievements

Optic atrophy 1 (OPA1) 遺伝子変異による遺伝性視神経症である常染色体優性視神経萎縮症 (autosomal dominant optic atrophy: ADOA) は幼少期より視機能障害が生じる治療困難な疾患である。視神経は組織採取して研究を行うことが困難な臓器の一つであるが、ヒトiPS細胞を使用することにより患者の視神経を採取することなく研究することが可能になった。さらにOPA1遺伝子変異がもたらすミトコンドリア機能障害が視神経委縮と関連している可能性が高いことから、同様に視神経障害を来す緑内障においてもミトコンドリア機能障害が関連している可能性が示唆される。

Report

(3 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • Research Products

    (2 results)

All 2020

All Presentation (2 results) (of which Invited: 2 results)

  • [Presentation] Investigation of glaucoma-related neuropathy using human iPSC-derived 3D retinal organoids2020

    • Author(s)
      小林 航
    • Organizer
      第124回日本眼科学会総会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Analysis of human retinal ganglion cells using induced pluripotent stem cells2020

    • Author(s)
      小林 航
    • Organizer
      第31回日本緑内障学会
    • Related Report
      2020 Annual Research Report
    • Invited

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Published: 2019-04-18   Modified: 2022-01-27  

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