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The role of progranulin in retinal regeneration

Research Project

Project/Area Number 16K11325
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Ophthalmology
Research InstitutionGifu Pharmaceutical University

Principal Investigator

Hara Hideaki  岐阜薬科大学, 薬学部, 教授 (20381717)

Co-Investigator(Kenkyū-buntansha) 鶴間 一寛  岐阜薬科大学, 薬学部, 講師 (50524980)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
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)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsProgranulin / microglia / retinal regeneration / retinal development / プログラニュリン / ミクログリア / 網膜発生 / 網膜再生 / アストロサイト / HGF受容体 / 網膜 / 網膜神経節細胞 / 再生医学 / 神経科学
Outline of Final Research Achievements

Progranulin is a growth factor which leads to neurogenesis. Previously, we found that progranulin induces retinal regeneration in mice. However, little is known that the mechanism of progranulin to leads retinal regeneration. In this study, we investigated that the influence of progranulin deficiency during retinal development using progranulin knockout mice.
In progranuline knockout mice, we found that retinal ganglion cells are degenerated. In progranulin knock out mice, retinal precursor cells and microglia were also decreased on postnatal day 9. Collectively, we found that the novel mechanisms of progranulin which contribute to retinal development and retinal regeneration.

Academic Significance and Societal Importance of the Research Achievements

本研究においては、網膜再生を誘導する成長因子であるプログラニュリンの作用について詳細な検討を行った。その作用機序の一端を明らかにしただけでなく、ミクログリアによる網膜前駆細胞増殖の制御などの新たな機構についても明らかとした。これらのことは学術的な新規性を有しているのみならず、未だ達成されていない哺乳類における網膜の再生制御を行うための重要な知見であり、本研究の実施は網膜再生医療の新たな発展に貢献するものである。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (43 results)

All 2019 2018 2017 2016

All Journal Article (23 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 23 results,  Open Access: 16 results,  Acknowledgement Compliant: 1 results) Presentation (19 results) (of which Int'l Joint Research: 3 results,  Invited: 5 results) Book (1 results)

  • [Journal Article] Effects of ripasudil, a ROCK inhibitor, on retinal edema and nonperfusion area in a retinal vein occlusion murine model.2018

    • Author(s)
      Hida Y, Nakamura S, Nishinaka A, Inoue Y, Shimazawa M and Hara H
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 137 Issue: 2 Pages: 129-136

    • DOI

      10.1016/j.jphs.2018.06.010

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Irreversible Photoreceptors and RPE Cells Damage by Intravenous Sodium Iodate in Mice Is Related to Macrophage Accumulation2018

    • Author(s)
      Moriguchi Mayu、Nakamura Shinsuke、Inoue Yuki、Nishinaka Anri、Nakamura Maho、Shimazawa Masamitsu、Hara Hideaki
    • Journal Title

      Investigative Opthalmology & Visual Science

      Volume: 59 Issue: 8 Pages: 3476-3476

    • DOI

      10.1167/iovs.17-23532

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Microglia increases the proliferation of retinal precursor cells during postnatal development2018

    • Author(s)
      Kuse Y, Ohuchi K, Nakamura S, Hara H and Shimazawa M
    • Journal Title

      Molecular Vision

      Volume: 24 Pages: 536-545

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Exposure to excessive blue LED light damages retinal pigment epithelium and photoreceptors of pigmented mice2018

    • Author(s)
      Nakamura Maho、Yako Tomohiro、Kuse Yoshiki、Inoue Yuki、Nishinaka Anri、Nakamura Shinsuke、Shimazawa Masamitsu、Hara Hideaki
    • Journal Title

      Experimental Eye Research

      Volume: 177 Pages: 1-11

    • DOI

      10.1016/j.exer.2018.07.022

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intravitreal aflibercept protects photoreceptors of mice against excessive light exposure2018

    • Author(s)
      Kuse Yoshiki、Takahashi Kei、Inoue Yuki、Izawa Hiroshi、Nakamura Shinsuke、Shimazawa Masamitsu、Hara Hideaki
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 137 Issue: 4 Pages: 407-411

    • DOI

      10.1016/j.jphs.2018.07.010

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pathophysiological Role of VEGF on Retinal Edema and Nonperfused Areas in Mouse Eyes With Retinal Vein Occlusion2018

    • Author(s)
      Nishinaka Anri、Inoue Yuki、Fuma Shinichiro、Hida Yoshifumi、Nakamura Shinsuke、Shimazawa Masamitsu、Hara Hideaki
    • Journal Title

      Investigative Opthalmology & Visual Science

      Volume: 59 Issue: 11 Pages: 4701-4701

    • DOI

      10.1167/iovs.18-23994

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transient acceleration of autophagic degradation by pharmacological Nrf2 activation is important for retinal pigment epithelium cell survival2018

    • Author(s)
      Saito Yuichi、Kuse Yoshiki、Inoue Yuki、Nakamura Shinsuke、Hara Hideaki、Shimazawa Masamitsu
    • Journal Title

      Redox Biology

      Volume: 19 Pages: 354-363

    • DOI

      10.1016/j.redox.2018.09.004

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Granulin 1 Promotes Retinal Regeneration in Zebrafish2018

    • Author(s)
      Tsuruma Kazuhiro、Saito Yuichi、Okuyoshi Hiroyuki、Yamaguchi Akihiro、Shimazawa Masamitsu、Goldman Daniel、Hara Hideaki
    • Journal Title

      Investigative Opthalmology & Visual Science

      Volume: 59 Issue: 15 Pages: 6057-6057

    • DOI

      10.1167/iovs.18-24828

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Progranulin deficiency causes the retinal ganglion cell loss during development2017

    • Author(s)
      Kuse Yoshiki、Tsuruma Kazuhiro、Mizoguchi Takahiro、Shimazawa Masamitsu、Hara Hideaki
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 1679-1679

    • DOI

      10.1038/s41598-017-01933-8

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] CCR3 Is Associated with the Death of a Photoreceptor Cell-line Induced by Light Exposure2017

    • Author(s)
      Kuse Yoshiki、Tsuruma Kazuhiro、Kanno Yusuke、Shimazawa Masamitsu、Hara Hideaki
    • Journal Title

      Frontiers in Pharmacology

      Volume: 8 Pages: 1-8

    • DOI

      10.3389/fphar.2017.00207

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Progranulin increases phagocytosis by retinal pigment epithelial cells in culture2017

    • Author(s)
      Murase Hiromi、Tsuruma Kazuhiro、Kuse Yoshiki、Shimazawa Masamitsu、Hara Hideaki
    • Journal Title

      Journal of Neuroscience Research

      Volume: 95 Issue: 12 Pages: 2500-2510

    • DOI

      10.1002/jnr.24081

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Astaxanthin analogs, adonixanthin and lycopene, activate Nrf2 to prevent light-induced photoreceptor degeneration2017

    • Author(s)
      Inoue Yuki、Shimazawa Masamitsu、Nagano Ryota、Kuse Yoshiki、Takahashi Kei、Tsuruma Kazuhiro、Hayashi Masahiro、Ishibashi Takashi、Maoka Takashi、Hara Hideaki
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 134 Issue: 3 Pages: 147-157

    • DOI

      10.1016/j.jphs.2017.05.011

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of kallidinogenase on retinal edema and size of non-perfused areas in mice with retinal vein occlusion2017

    • Author(s)
      Nishinaka Anri、Fuma Shinichiro、Inoue Yuki、Shimazawa Masamitsu、Hara Hideaki
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 134 Issue: 2 Pages: 86-92

    • DOI

      10.1016/j.jphs.2017.05.003

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] GPNMB Induces BiP Expression by Enhancing Splicing of BiP Pre-mRNA during the Endoplasmic Reticulum Stress Response2017

    • Author(s)
      Noda Yasuhiro、Tsuruma Kazuhiro、Takata Masafumi、Ishisaka Mitsue、Tanaka Hirotaka、Nakano Yusuke、Nagahara Yuki、Shimazawa Masamitsu、Hara Hideaki
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 12160-12160

    • DOI

      10.1038/s41598-017-11828-3

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effects of ticagrelor in a mouse model of ischemic stroke2017

    • Author(s)
      Yamauchi Keita、Imai Takahiko、Shimazawa Masamitsu、Iwama Toru、Hara Hideaki
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1 Pages: 12088-12088

    • DOI

      10.1038/s41598-017-12205-w

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Platelet-Derived Growth Factor-BB Lessens Light-Induced Rod Photoreceptor Damage in Mice2017

    • Author(s)
      Takahashi Kei、Shimazawa Masamitsu、Izawa Hiroshi、Inoue Yuki、Kuse Yoshiki、Hara Hideaki
    • Journal Title

      Investigative Opthalmology & Visual Science

      Volume: 58 Issue: 14 Pages: 6299-6299

    • DOI

      10.1167/iovs.17-22556

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Both Autocrine Signaling and Paracrine Signaling of HB-EGF Enhance Ocular NeovascularizationHighlights2017

    • Author(s)
      Inoue Yuki、Shimazawa Masamitsu、Nakamura Shinsuke、Takata Shinsuke、Hashimoto Yuhei、Izawa Hiroshi、Masuda Tomomi、Tsuruma Kazuhiro、Sakaue Tomohisa、Nakayama Hironao、Higashiyama Shigeki、Hara Hideaki
    • Journal Title

      Arteriosclerosis, Thrombosis, and Vascular Biology

      Volume: 38 Issue: 1 Pages: 174-185

    • DOI

      10.1161/atvbaha.117.310337

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cilostazol ameliorates collagenase-induced cerebral hemorrhage by protecting the blood brain barrier2017

    • Author(s)
      Takagi T, Imai T, Mishiro K, Ishisaka M, Tsujimoto M, Ito H, Nagashima K, Matsukawa H, Tsuruma K, Shimazawa M, Yoshimura S, Kozawa O, Iwama T, Hara H.
    • Journal Title

      J Cereb Blood Flow Metab.

      Volume: 37 Issue: 1 Pages: 123-139

    • DOI

      10.1177/0271678x15621499

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Nrf2 protects photoreceptor cells from photo-oxidative stress induced by blue light.2017

    • Author(s)
      Wan-Ju Chen, Caiying Wu, Zhenhua Xu, Kuse Y., Hara H. and Elia Duh.
    • Journal Title

      Exp. Eye Res.

      Volume: 154 Pages: 151-158

    • DOI

      10.1016/j.exer.2016.12.001

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Apolipoprotein E2 and E3, but not E4, promote retinal pathological neovascularization2017

    • Author(s)
      Masuda T., Shimazawa M., Hashimoto Y., Kojima A., Nakamura S., Suemori S., Mochizuki K., Kawakami H., Kawase K., and Hara H.
    • Journal Title

      Investigative Ophthalmology & Visual Science

      Volume: 58 Issue: 2 Pages: 1208-1217

    • DOI

      10.1167/iovs.16-20539

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] A pharmacological approach in newly established retinal vein occlusion model2017

    • Author(s)
      Fuma S., Nishinaka A., Inoue Y., Tsuruma K., Shimazawa M., Kondo M. and Hara H
    • Journal Title

      Scientific Reports

      Volume: 7, 43509 Issue: 1 Pages: 43509-43509

    • DOI

      10.1038/srep43509

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] RS9, a novel Nrf2 activator, attenuates light-induced death of cells of photoreceptor cells and Muller glia cells.2017

    • Author(s)
      Inoue Y., Shimazawa M., Noda Y., Nagano R., Otsuka T., Kuse Y., Nakano Y., Tsuruma K., Nakagami Y. and Hara H.
    • Journal Title

      Journal of Neurochemistry

      Volume: 印刷中 Issue: 5 Pages: 750-765

    • DOI

      10.1111/jnc.14029

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Protective effects of NSP-116, a novel imidazolyl aniline derivative, against light-induced retinal damage in vitro and in vivo2016

    • Author(s)
      Izawa H., Shimazawa M., Inoue Y., Uchida S., Moroe H., Tsuruma K. and Hara H.
    • Journal Title

      Free Radic. Biol. Med

      Volume: 96 Pages: 304-312

    • DOI

      10.1016/j.freeradbiomed.2016.03.036

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Presentation] オートリソソーム形成を介したαシヌクレイン蓄積におけるProgranulinの関与2019

    • Author(s)
      大庭 卓也、中村 信介、嶋澤 雅光、原 英彰
    • Organizer
      第92回日本薬理学会年会(大阪、3/14-16)
    • Related Report
      2018 Annual Research Report
  • [Presentation] プログラニュリン及び切断産物グラニュリンの網膜視細胞保護に関する研究2018

    • Author(s)
      田中美留豊,久世祥己,中村信介,嶋澤雅光,原英彰
    • Organizer
      第3回プログラニュリン研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 加齢黄斑変性におけるプログラニュリンの関与2018

    • Author(s)
      髙橋慶,中村信介,嶋澤雅光,原英彰
    • Organizer
      第3回プログラニュリン研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Adiponectin is a pathological factor for intraocular angiogenesis2018

    • Author(s)
      Nakamura S, Masuda T, Sakurai S, Kawakami H, Suemori S, Mochizuki K, Shimazawa M, Hara H
    • Organizer
      18th World Congress of Basic and Clinical Pharmacology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A novel Nrf2 activator RS9 protects ARPE-19 cells from oxidative stress induced by NaIO3 via autophagic pathway2018

    • Author(s)
      Saito Y, Nakamura S, Shimazawa M, Hara H
    • Organizer
      18th World Congress of Basic and Clinical Pharmacology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ゼブラフィッシュ網膜再生における血小板由来成長因子 (PDGF) の関与2018

    • Author(s)
      山口明洋、齋藤祐一、奥吉博之、中村信介、嶋澤雅光、原英彰
    • Organizer
      第38回日本眼薬理学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 視細胞障害における脂肪細胞由来幹細胞の作用及び網膜静脈閉塞症におけるVEGFの役割に関する研究2018

    • Author(s)
      原英彰
    • Organizer
      大阪大学蛋白研究所セミナー
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 視神経細胞保護作用に関する基礎研究の現状とビルベリ―由来機能性食品の効果2018

    • Author(s)
      原英彰
    • Organizer
      第122回 日本眼科学会総会
    • Related Report
      2017 Research-status Report
  • [Presentation] The pathophysiological roles of vascular endothelial growth factor (VEGF) on retinal edema and nonperfusion areas in retinal vein occlusion murine model.2018

    • Author(s)
      Nishinaka A, Inoue Y, Fuma S, Hida Y, Nakamura S, Shimazawa M, Hara H
    • Organizer
      ARVO 2018 Annual Meeting
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 網膜血管新生の基礎―網膜血管新生動物モデルの確立と新規治療薬の可能性―2017

    • Author(s)
      原英彰
    • Organizer
      第90回日本薬理学会年会
    • Place of Presentation
      長崎
    • Year and Date
      2017-03-15
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] Astrocyte activation and retinal ganglion cell loss during retinal development in progranulin deficient mice.2017

    • Author(s)
      久世祥己、鶴間一寛、溝口貴洋、嶋澤雅光、原英彰
    • Organizer
      第90回日本薬理学会年会
    • Place of Presentation
      長崎
    • Year and Date
      2017-03-15
    • Related Report
      2016 Research-status Report
  • [Presentation] マウス網膜発生期におけるプログラニュリンの役割2017

    • Author(s)
      久世祥己、鶴間一寛、嶋澤雅光、原英彰
    • Organizer
      第2回プログラニュリン研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] マウス網膜静脈閉塞症モデルにおける血管内皮増殖因子の発現及び局在変化2017

    • Author(s)
      西中杏里、井上雄有輝、肥田禎史、嶋澤雅光、原英彰
    • Organizer
      第37回日本眼薬理学会
    • Related Report
      2017 Research-status Report
  • [Presentation] マウス網膜発生期におけるミクログリアの関与2017

    • Author(s)
      久世祥己、大内一輝、中村信介、嶋澤雅光、原英彰
    • Organizer
      第132回日本薬理学会近畿部会
    • Related Report
      2017 Research-status Report
  • [Presentation] 脳梗塞に対する脂肪組織由来幹細胞培養上清の基礎的検討2017

    • Author(s)
      原英彰、江頭裕介、岩間亨
    • Organizer
      第60回日本脳循環代謝学会学術集会
    • Related Report
      2017 Research-status Report
  • [Presentation] LEDは動物飼育や動物実験にどう影響を及ぼすのか?2017

    • Author(s)
      原英彰
    • Organizer
      日本実験動物技術者協会 関西支部設立50周年記念大会
    • Place of Presentation
      神戸
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] Neuroprotective effects of the conditioned-medium of murine and human adipose-derived stem cells on experimental retinal degeneration and stroke models.2016

    • Author(s)
      Hara H
    • Organizer
      International Conference of Neurodegenerative Diseases and Brain Injuries
    • Place of Presentation
      Weifang Ciity、Shandong、China
    • Year and Date
      2016-10-28
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] Neuroprotective effects of the conditioned medium of murine and human adipose-derived stem cells on experimental stroke models.2016

    • Author(s)
      Hara H
    • Organizer
      9th Pan Pacific Symposium on Stem Cells and Cancer Research
    • Place of Presentation
      台湾、台北
    • Year and Date
      2016-05-14
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] マウス網膜再生におけるプログラニュリンの機能解析2016

    • Author(s)
      久世祥己 鶴間一寛 嶋澤雅光 原英彰
    • Organizer
      第1回プログラニュリン研究会
    • Place of Presentation
      岐阜
    • Related Report
      2016 Research-status Report
  • [Book] Progranulin and Central Nervous System Disorders2019

    • Author(s)
      Hara, H., Hosokawa, M., Nakamura, S., Shimohata, T., Nishihara, M.
    • Total Pages
      183
    • Publisher
      Springer
    • Related Report
      2018 Annual Research Report

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Published: 2016-04-21   Modified: 2020-03-30  

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