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Developmental analysis of retinal ganglion cell derived from human ES/iPS cells

Research Project

Project/Area Number 17K16996
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Ophthalmology
Research InstitutionNational Center for Child Health and Development

Principal Investigator

Tadashi Yokoi  国立研究開発法人国立成育医療研究センター, 感覚器・形態外科部, 医師 (80514025)

Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsヒトiPS細胞 / 網膜神経節細胞 / Brn3b / NGF / Semaphorin3A / 軸索再生 / iPS / 軸索伸長 / ヒトiPS
Outline of Final Research Achievements

We have generated the functioning retinal ganglion cells (RGCs) with axons derived from human iPSCs. Determination of RGC lineage is almost completed after the expression of Brn3b, and RGCs elongate their axons, thereafter. In this in-vitro RGCs generation model, there have been little knowledge regarding the factors associated with their axonal development. In this study, we demonstrated that the axons of human RGCs responded to the known neurotrophic factors, including neruo-attractive and neuro-repulsive factors. The human RGCs significantly elongates their axons by the administration of nerve growth factor, but reduced them by semaphorin3A. We further aim to reveal the molecular signaling associated RGC development, using this in vitro system.

Academic Significance and Societal Importance of the Research Achievements

現在、我が国における失明原因の1位は緑内障であり、これは、網膜神経節細胞の細胞死によって引き起こされる。また、網膜神経節細胞の細胞死による眼科疾患は、緑内障の他、遺伝性視神経症や視神経炎をはじめとして様々な疾患が存在する。これら治療法の開発には、ヒト由来の網膜神経節細胞を得ることが非常に有用であり、我々の研究室ではヒトiPSから網膜神経節細胞を樹立した。今回、本細胞を用いて、神経分化にかかわる因子についてその作用を検討し、軸索成長についての知見が得られた。今後疾患治療のための軸索再生等に向けた、さらなる研究を遂行する予定である。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (5 results)

All 2019 2017

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 5 results,  Open Access: 5 results)

  • [Journal Article] Foveal Neovascularization Detected by Optical Coherence Tomography Angiography in Incontinentia Pigmenti2019

    • Author(s)
      Tanaka Shin、Yokoi Tadashi、Azuma Noriyuki
    • Journal Title

      JAMA Ophthalmology

      Volume: 137 Issue: 3 Pages: e184197-e184197

    • DOI

      10.1001/jamaophthalmol.2018.4197

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Optical coherence tomography and video recording of a case of bilateral contractile peripapillary staphyloma2019

    • Author(s)
      Yoshida Tomoyo、Katagiri Satoshi、Yokoi Tadashi、Nishina Sachiko、Azuma Noriyuki
    • Journal Title

      American Journal of Ophthalmology Case Reports

      Volume: 13 Pages: 66-69

    • DOI

      10.1016/j.ajoc.2018.12.002

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Characteristics of Retinal Breaks and Surgical Outcomes in Rhegmatogenous Retinal Detachment in Familial Exudative Vitreoretinopathy2017

    • Author(s)
      Katagiri Satoshi、Yokoi Tadashi、Yoshida-Uemura Tomoyo、Nishina Sachiko、Azuma Noriyuki
    • Journal Title

      Ophthalmology Retina

      Volume: 5 Issue: 7 Pages: 76-80

    • DOI

      10.1016/j.oret.2017.11.003

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ATYPICAL FORM OF RETINOPATHY OF PREMATURITY WITH SEVERE FIBROVASCULAR PROLIFERATION IN THE OPTIC DISC REGION2017

    • Author(s)
      Yokoi T, Katagiri S, Hiraoka M, Nakayama Y, Hosono K, Hotta Y, Nishina S, Azuma N
    • Journal Title

      RETINA

      Volume: 印刷中 Issue: 8 Pages: 1-1

    • DOI

      10.1097/iae.0000000000001779

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effects of neuroactive agents on axonal growth and pathfinding of retinal ganglion cells generated from human stem cells2017

    • Author(s)
      Yokoi Tadashi、Tanaka Taku、Matsuzaka Emiko、Tamalu Fuminobu、Watanabe Shu-Ichi、Nishina Sachiko、Azuma Noriyuki
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 16757-16757

    • DOI

      10.1038/s41598-017-16727-1

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access

URL: 

Published: 2017-04-28   Modified: 2020-03-30  

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