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Probing the effect of degenerated retina potentiation on the synaptogenesis after iPSC-derived retinal transplantation

Research Project

Project/Area Number 17K16994
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Ophthalmology
Research InstitutionInstitute of Physical and Chemical Research

Principal Investigator

Tu Hung-Ya  国立研究開発法人理化学研究所, 生命機能科学研究センター, 研究員 (10780835)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordstransplantation / organoid / retinal degeneration / amacrine cell / electrophysiology / ganglion cell / retinal organoid / amarine cell / MEA / retinal transplantation / multi-electrode arrary / rod bipolar cell / AII amacrine cell / 神経科学
Outline of Final Research Achievements

While fundamental properties of the normal retinal wiring are largely revealed in the past several decades, other counterintuitive but intriguing properties have recently been explored from diseased retinal models. The inner retinal hyperactivity has been commonly seen in deafferented retinas, in which many of the residual retinal ganglion cells are found exhibiting rhythmic membrane potential oscillation and spontaneous spiking activity. However, whether the inner retinal hyperactivity would affect the reconstruction of retinal circuitry remains unclear. The present study is therefore aimed to probe the effect of pharmacological suppression of inner retinal hyperactivity on retinal reconstruction after stem cell-derived retinal transplantation. By MEA recording, the systematic functional evaluation method of transplanted retinas has been established and used to compare the light responsiveness in transplanted mice treated with or without inner retinal hyperactivity blockade.

Academic Significance and Societal Importance of the Research Achievements

Although the present study is still preliminary with much room for improvement technically, the results indicate the potential of host retina manipulation to optimize retinal transplantation therapy, and lead to the idea for a more thorough investigation in the following KAKENHI study.

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (11 results)

All 2020 2019 2018

All Journal Article (6 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 4 results,  Open Access: 5 results) Presentation (5 results) (of which Int'l Joint Research: 5 results)

  • [Journal Article] Multielectrode Array Recording of Mouse Retinas Transplanted with Stem Cell-Derived Retinal Sheets2020

    • Author(s)
      Hung-Ya Tu, Take Matsuyama
    • Journal Title

      Retinal Development. Methods in Molecular Biology

      Volume: 2092 Pages: 207-220

    • DOI

      10.1007/978-1-0716-0175-4_15

    • ISBN
      9781071601747, 9781071601754
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Journal Article] Medium- to long-term survival and functional examination of human iPSC-derived retinas in rat and primate models of retinal degeneration2019

    • Author(s)
      Tu Hung-Ya、Watanabe Takehito、Shirai Hiroshi、Yamasaki Suguru、Kinoshita Masaharu、Matsushita Keizo、Hashiguchi Tomoyo、Onoe Hirotaka、Matsuyama Take、Kuwahara Atsushi、Kishino Akiyoshi、Kimura Toru、Eiraku Mototsugu、Suzuma Kiyoshi、Kitaoka Takashi、Takahashi Masayo、Mandai Michiko
    • Journal Title

      EBioMedicine

      Volume: 39 Pages: 562-574

    • DOI

      10.1016/j.ebiom.2018.11.028

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Quantitative and Qualitative Evaluation of Photoreceptor Synapses in Developing, Degenerating and Regenerating Retinas2019

    • Author(s)
      Akiba Ryutaro、Matsuyama Take、Tu Hung-Ya、Hashiguchi Tomoyo、Sho Junki、Yamamoto Shuichi、Takahashi Masayo、Mandai Michiko
    • Journal Title

      Frontiers in Cellular Neuroscience

      Volume: 13

    • DOI

      10.3389/fncel.2019.00016

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Genetically engineered iPSC-retina for improved retinal reconstruction after transplantation2018

    • Author(s)
      Tu Hung-Ya、Matsuyama Takesi、Sun Jianan、Hashiguchi Tomoyo、Sho Junki、Sunagawa Genshiro A.、Fujii Momo、Onishi Akishi、Takahashi Masayo、Mandai Michiko
    • Journal Title

      Investigative Ophthalmology & Visual Science

      Volume: 59 Pages: 1987-1987

    • Related Report
      2018 Research-status Report
    • Open Access / Int'l Joint Research
  • [Journal Article] Establishment of Immunodeficient Retinal Degeneration Model Mice and Functional Maturation of Human ESC-Derived Retinal Sheets after Transplantation2018

    • Author(s)
      Iraha Satoshi、Tu Hung-Ya、Yamasaki Suguru、Kagawa Takahiro、Goto Motohito、Takahashi Riichi、Watanabe Takehito、Sugita Sunao、Yonemura Shigenobu、Sunagawa Genshiro A.、Matsuyama Take、Fujii Momo、Kuwahara Atsushi、Kishino Akiyoshi、Koide Naoshi、Eiraku Mototsugu、Tanihara Hidenobu、Takahashi Masayo、Mandai Michiko
    • Journal Title

      Stem Cell Reports

      Volume: 10 Issue: 3 Pages: 1059-1074

    • DOI

      10.1016/j.stemcr.2018.01.032

    • NAID

      120007037461

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Culture Systems of Dissociated Mouse and Human Pluripotent Stem Cell?Derived Retinal Ganglion Cells Purified by Two-Step Immunopanning2018

    • Author(s)
      Kobayashi Wataru、Onishi Akishi、Tu Hung-Ya、Takihara Yuji、Matsumura Michiru、Tsujimoto Kazuko、Inatani Masaru、Nakazawa Toru、Takahashi Masayo
    • Journal Title

      Investigative Opthalmology & Visual Science

      Volume: 59 Issue: 2 Pages: 776-776

    • DOI

      10.1167/iovs.17-22406

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Functional examination of genetically engineered human ESC-retinas transplanted in an immunodeficient rat model with retinal degeneration2019

    • Author(s)
      Hung-Ya Tu; Suguru Yamasaki; atsushi kuwahara; Akiyoshi Kishino; Toru Kimura; Masayo Takahashi; Michiko Mandai
    • Organizer
      ARVO Annual Meeting 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Effect of ambient light and BDNF on photoreceptor synaptogenesis after mouse ESC/iPSC-derived retinal organoid transplantation2019

    • Author(s)
      Ryutaro Akiba; Take Matsuyama; Hung-Ya Tu; Tomoyo Hashiguchi; Sho Junki; Shuichi Yamamoto; Yasuhiko Tabata; Masayo Takahashi; Michiko Mandai
    • Organizer
      ARVO Annual Meeting 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Functional examination of genetically engineered human ESC-retinas transplanted in an immunodeficient rat model with retinal degeneration2019

    • Author(s)
      Tu Hung-Ya, Yamasaki Suguru, Matsuyama Take, Kuwahara Atsushi, Kishino Akiyoshi, Kimura Toru, Takahashi Masayo, Mandai Michiko
    • Organizer
      ARVO Annual Meeting 2019
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Functional integration of human ESC-derived retinal sheets after transplantation into immune-deficient retinal degeneration mice2018

    • Author(s)
      Tu Hung-Ya, Iraha Satoshi, Yamasaki Suguru, Matsuyama Take, Sunagawa Genshiro A., Watanabe Takehito, Hashiguchi Tomoyo, Sho Junki, Takahashi Masayo, Mandai Michiko
    • Organizer
      TERMIS World Congress 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Genetically engineered iPSC-retina for improved retinal reconstruction after transplantation2018

    • Author(s)
      Hung-Ya Tu, Take Matsuyama, Jianan Sun, Tomoyo Hashiguchi, Junki Sho, Genshiro A. Sunagawa, Momo Fujii, Akishi Onishi, Masayo Takahashi, Michiko Mandai
    • Organizer
      ARVO Annual Meeting 2018
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2021-02-19  

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