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Development of new treatment for age-related macular degeneration

Research Project

Project/Area Number 16K11285
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Ophthalmology
Research InstitutionKyoto University

Principal Investigator

IKEDA Hanako  京都大学, 医学研究科, 准教授 (20372162)

Co-Investigator(Kenkyū-buntansha) 村岡 勇貴  京都大学, 医学研究科, 助教 (00739089)
畑 匡侑  京都大学, 医学研究科, 助教 (70748269)
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: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords加齢黄斑変性 / ドルーゼン / 治療 / 失明予防 / iPS細胞 / 新規治療法開発
Outline of Final Research Achievements

We have been investigating the pathophysiology and development of a new treatment method for age-related macular degeneration. We developed an inhibitor for the ATPase of valocin-containing protein (VCP), which suppressed the increase in drusen-like deposits in CCr2 knockout mice and drusen monkeys. Studies on iPS cells revealed that the retinal pigment epithelium morphology in the iPS cells of patients did not differ from those of normal individuals. Drusen formation on membranes of the iPS-derived retinal pigment epithelium was more active in patients than in normal individuals.

Academic Significance and Societal Importance of the Research Achievements

これまで病変組織の採取が難しく、加齢黄斑変性に対する病態研究は困難であったが、本研究の手法を用いることで、研究が進むと考えられ、その学術的意義は非常に大きいと考える。
また、加齢黄斑変性の前駆症状であるドルーゼンを消失させる薬剤は、実用化されたものがなく、本研究で明らかになった、ドルーゼン消失作用を持つVCP ATPase阻害剤が臨床応用されれば、多くの患者の失明予防につながると考えられ、その社会的意義は非常に大きいと考えられる。

Report

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

    (52 results)

All 2019 2018 2017 2016 Other

All Journal Article (16 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 14 results,  Open Access: 13 results,  Acknowledgement Compliant: 2 results) Presentation (30 results) (of which Invited: 25 results) Remarks (4 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 2 results)

  • [Journal Article] Adenosine triphosphate maintenance by branched chain amino acids as a novel neuroprotective strategy for retinal neurodegenerative diseases2019

    • Author(s)
      Ikeda HanakoOhashi、Hasegawa Tomoko
    • Journal Title

      Neural Regeneration Research

      Volume: 14 Issue: 1 Pages: 82-82

    • DOI

      10.4103/1673-5374.244788

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Conjunctival and Intrascleral Vasculatures Assessed Using Anterior Segment Optical Coherence Tomography Angiography in Normal Eyes2018

    • Author(s)
      Akagi Tadamichi、Uji Akihito、Huang Alex S.、Weinreb Robert N.、Yamada Tatsuya、Miyata Manabu、Kameda Takanori、Ikeda Hanako Ohashi、Tsujikawa Akitaka
    • Journal Title

      American Journal of Ophthalmology

      Volume: 196 Pages: 1-9

    • DOI

      10.1016/j.ajo.2018.08.009

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Visualization of the Lamina Cribrosa Microvasculature in Normal and Glaucomatous Eyes: A Swept-source Optical Coherence Tomography Angiography Study.2018

    • Author(s)
      Numa S, Akagi T, Uji A, Suda K, Nakanishi H, Kameda T, Ikeda HO, Tsujikawa A.
    • Journal Title

      J Glaucoma

      Volume: 27 Issue: 11 Pages: 1032-1035

    • DOI

      10.1097/ijg.0000000000001069

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of Structure-Function Relationships in Longitudinal Changes of Glaucoma using the Spectralis OCT Follow-Up Mode2018

    • Author(s)
      Suda Kenji、Akagi Tadamichi、Nakanishi Hideo、Noma Hisashi、Ikeda Hanako Ohashi、Kameda Takanori、Hasegawa Tomoko、Tsujikawa Akitaka
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 17158-17158

    • DOI

      10.1038/s41598-018-35419-y

    • NAID

      120006541994

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Relationship between Ocular Deviation and Visual Function in Retinitis Pigmentosa2018

    • Author(s)
      Miyata Manabu、Oishi Akio、Ogino Ken、Oishi Maho、Hasegawa Tomoko、Nagasaku Yuko、Ikeda Hanako Ohashi、Ohtsuki Hiroshi、Tsujikawa Akitaka
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 30291281-30291281

    • DOI

      10.1038/s41598-018-33211-6

    • NAID

      120006529729

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] KUS121, an ATP regulator, mitigates chorioretinal pathologies in animalmodels of age-related macular degeneration.2018

    • Author(s)
      Muraoka, Y., Yoshimura, N., et al.
    • Journal Title

      Heliyon

      Volume: 4 Issue: 5 Pages: e00624-e00624

    • DOI

      10.1016/j.heliyon.2018.e00624

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Reduction of lipid accumulation rescues Bietti’s crystalline dystrophy phenotypes2018

    • Author(s)
      Hata Masayuki、Ikeda Hanako O.、Iwai Sachiko、Iida Yuto、Gotoh Norimoto、Asaka Isao、Ikeda Kazutaka、Isobe Yosuke、Hori Aya、Nakagawa Saori、Yamato Susumu、Arita Makoto、Yoshimura Nagahisa、Tsujikawa Akitaka
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 115 Issue: 15 Pages: 3936-3941

    • DOI

      10.1073/pnas.1717338115

    • NAID

      120006416205

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Branched chain amino acids attenuate major pathologies in mouse models of retinal degeneration and glaucoma2018

    • Author(s)
      Hasegawa Tomoko、Ikeda Hanako Ohashi、Iwai Sachiko、Muraoka Yuki、Tsuruyama Tatsuaki、Okamoto-Furuta Keiko、Kohda Haruyasu、Kakizuka Akira、Yoshimura Nagahisa
    • Journal Title

      Heliyon

      Volume: 4 Issue: 2 Pages: e00544-e00544

    • DOI

      10.1016/j.heliyon.2018.e00544

    • NAID

      120006425863

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Association of Bruch's membrane opening and optic disc morphology to axial length and visual field defects in eyes with primary open-angle glaucoma2018

    • Author(s)
      Nakanishi H, Suda K, Yoshikawa M, Akagi T, Kameda T, Ikeda HO, Yokota S, Kurimoto Y, Tsujikawa A
    • Journal Title

      Graefes Arch Clin Exp Ophthalmol

      Volume: 256 Issue: 3 Pages: 599-610

    • DOI

      10.1007/s00417-017-3874-8

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Modulation of valosin-containing protein by Kyoto University Substances (KUS) as a novel therapeutic strategy for ischemic neuronal diseases2017

    • Author(s)
      Ikeda HanakoOhashi、Hata Masayuki
    • Journal Title

      Neural Regeneration Research

      Volume: 12 Issue: 8 Pages: 1252-1252

    • DOI

      10.4103/1673-5374.213540

    • NAID

      120006870290

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Association of Glaucoma-Susceptible Genes to Regional Circumpapillary Retinal Nerve Fiber Layer Thickness and Visual Field Defects2017

    • Author(s)
      Yoshikawa M, Nakanishi H, Yamashiro K, Miyake M, Akagi T, Gotoh N, Ikeda HO, Suda K, Yamada H, Hasegawa T, Iida Y, Yamada R, Matsuda F, Yoshimura N; Nagahama Study Group
    • Journal Title

      Invest Ophthalmol Vis Sci

      Volume: 58 Issue: 5 Pages: 2510-2519

    • DOI

      10.1167/iovs.16-20797

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] VCP阻害薬の臨床応用2017

    • Author(s)
      池田華子
    • Journal Title

      Retina Medicine

      Volume: 6 Pages: 17-21

    • Related Report
      2017 Research-status Report
  • [Journal Article] 網膜動脈閉塞症に対する神経保護治療の可能性2017

    • Author(s)
      池田 華子
    • Journal Title

      あたらしい眼科

      Volume: 34 Pages: 633-637

    • Related Report
      2017 Research-status Report
  • [Journal Article] KUS121, a VCP modulator, attenuates ischemic retinal cell death via suppressing endoplasmic reticulum stress.2017

    • Author(s)
      Hata M, Ikeda HO, Kikkawa C, Iwai S, Muraoka Y, Hasegawa T, Kakizuka A, Yoshimura N
    • Journal Title

      Sci Rep

      Volume: - Issue: 1 Pages: 44873-44873

    • DOI

      10.1038/srep44873

    • NAID

      120006222005

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Neuoroprotective efficacies by KUS121, a VCP modulator, on animal models of retinal degeneration.2016

    • Author(s)
      Hasegawa T, Muraoka Y, Ikeda HO, Tsuruyama T, Kondo M, Terasaki H, Kakizuka A, Yoshimura N.
    • Journal Title

      Sci Rep.

      Volume: 6 Issue: 1 Pages: 31184-31184

    • DOI

      10.1038/srep31184

    • NAID

      120005829364

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neuroprotective Effects of VCP Modulators in Mouse Models of Glaucoma.2016

    • Author(s)
      Nakano, N. et al.
    • Journal Title

      Heliyon

      Volume: 2 Issue: 4 Pages: 96-96

    • DOI

      10.1016/j.heliyon.2016.e00096

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 難治性眼疾患に対する新規神経保護治療法開発 ~網膜中心動脈閉塞症に対する医師主導治験~2019

    • Author(s)
      池田華子
    • Organizer
      AJOの会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 網膜中心動脈閉塞症に対するKUS121硝子体内投与による医師主導治験2018

    • Author(s)
      池田華子
    • Organizer
      第124回京都眼科学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 網膜色素変性に対する 新規神経保護治療開発2018

    • Author(s)
      池田華子
    • Organizer
      JRPS鹿児島 市民公開講座
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 新規神経保護治療薬の開発 -基礎研究から医師主導治験まで-2018

    • Author(s)
      池田華子
    • Organizer
      眼科若手研究者の会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] Development of a new neuroprotective treatment for glaucoma2018

    • Author(s)
      池田華子
    • Organizer
      第122回日本眼科学会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 網膜色素変性に対する 新規神経保護治療開発2018

    • Author(s)
      池田華子
    • Organizer
      JRPS香川 医療講演
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 緑内障に対する新規神経保護治療薬の開発2018

    • Author(s)
      池田華子
    • Organizer
      平成30年度豊中市眼科医会学術研究会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 眼難治疾患に対する新規神経保護治療法の開発2017

    • Author(s)
      池田華子
    • Organizer
      第19回大阪赤十字眼科フォーラム
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] Development of neuroprotective treatment using KUS for glaucoma2017

    • Author(s)
      池田華子
    • Organizer
      121回日本眼科学会総会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 眼疾患モデルを用いた 神経保護治療研究と創薬2017

    • Author(s)
      池田華子
    • Organizer
      121回日本眼科学会総会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 「網膜中心動脈閉塞症の薬物治療は可能か?」2017

    • Author(s)
      池田華子
    • Organizer
      121回日本眼科学会総会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 網膜色素変性に対する 新規神経保護治療開発2017

    • Author(s)
      池田華子
    • Organizer
      JRPS徳島 医療講演
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 眼難治疾患に対する 新規神経保護治療法の開発2017

    • Author(s)
      池田華子
    • Organizer
      第76回あやめ池眼科懇談会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 網膜色素変性に対する 新規神経保護治療開発2017

    • Author(s)
      池田華子
    • Organizer
      JRPS滋賀 医療講演
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 眼難治疾患に対する新規神経保護治療法開発2017

    • Author(s)
      池田華子
    • Organizer
      京都眼科学会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 網膜色素変性に対する 新規神経保護治療開発2017

    • Author(s)
      池田華子
    • Organizer
      JRPS神奈川 医療講演
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 網膜色素変性に対する 新規神経保護治療開発2017

    • Author(s)
      池田華子
    • Organizer
      JRPS東京 医療講演
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 網膜色素変性に対する 新規神経保護治療開発2017

    • Author(s)
      池田華子
    • Organizer
      JRPS埼玉6月 医療講演
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] VCP ATPase阻害剤による神経保護治療開発2017

    • Author(s)
      池田華子
    • Organizer
      第4回眼科創薬研究会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 眼難治疾患に対するVCP ATPase 阻害剤による新規神経保護治療法開発 ―基礎研究~医師主導治験―2017

    • Author(s)
      池田華子
    • Organizer
      生体機能と創薬シンポジウム2017
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 新規神経保護治療薬KUSの開発2017

    • Author(s)
      池田華子
    • Organizer
      第37回日本眼薬理学会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 神経保護治療研究 ー網膜中心動脈閉塞症に対する医師主導治験ー2017

    • Author(s)
      池田華子
    • Organizer
      27回愛知眼科フォーラム
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 新規神経保護治療薬による治療法開発2017

    • Author(s)
      池田華子
    • Organizer
      71回日本臨床眼科学会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 網膜中心動脈閉塞症に対する KUS121硝子体内投与による医師主導治験2017

    • Author(s)
      池田華子 村岡勇貴 畑匡侑 辻川明孝
    • Organizer
      京大眼科同窓会学会
    • Related Report
      2017 Research-status Report
  • [Presentation] VCP ATPase 阻害剤を用いた眼難治疾患に対する新規治療法開発2017

    • Author(s)
      池田華子
    • Organizer
      京都府立医科大学 眼科医局セミナー
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 失明を防ぐ ー眼の病気に対する神経保護治療研究ー2017

    • Author(s)
      池田華子
    • Organizer
      女子高生・車座フォーラム2017
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 失明を防ぐ ー眼の病気に対する神経保護治療研究ー2017

    • Author(s)
      池田華子
    • Organizer
      関西7大学フェスティバル2017
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] 網膜色素変性の視野進行評価と神経保護治療の取り組み2016

    • Author(s)
      長谷川智子、池田華子、村岡勇貴、後藤謙元、石原健司、菅原麻紗子、平島貴子、宮田学
    • Organizer
      京都眼科学会
    • Place of Presentation
      京都市
    • Related Report
      2016 Research-status Report
  • [Presentation] 網膜中心動脈閉塞症に対する神経保護治療法開発の取り組み2016

    • Author(s)
      池田華子、村岡勇貴、畑匡侑、村上智昭、飯田悠人、三輪裕子、鈴間潔、大音壮太郎
    • Organizer
      京都眼科学会
    • Place of Presentation
      京都市
    • Related Report
      2016 Research-status Report
  • [Presentation] 網膜中心動脈閉塞症に対する神経保護治療薬KUS121の開発2016

    • Author(s)
      池田華子, 村岡勇貴, 畑匡侑, 村上智昭, 飯田悠人, 三輪裕子, 鈴間潔, 大音壮太郎
    • Organizer
      京大眼科同窓会学会
    • Place of Presentation
      京都市
    • Related Report
      2016 Research-status Report
  • [Remarks] 京都大学眼科学教室

    • URL

      http://www.ophthalmol.kuhp.kyoto-u.ac.jp/

    • Related Report
      2018 Annual Research Report
  • [Remarks] 京都大学眼科学教室

    • URL

      https://www.facebook.com/ganka.kyoto/

    • Related Report
      2018 Annual Research Report
  • [Remarks] 京都大学網膜神経保護治療プロジェクト

    • URL

      http://www.ophthalmol.kuhp.kyoto-u.ac.jp/page_neuroprotection.html

    • Related Report
      2018 Annual Research Report
  • [Remarks] 網膜神経保護治療プロジェクト

    • URL

      http://www.ophthalmol.kuhp.kyoto-u.ac.jp/page_neuroprotection.html

    • Related Report
      2017 Research-status Report
  • [Patent(Industrial Property Rights)] 用途特許2018

    • Inventor(s)
      垣塚彰、池田華子、木下茂、中村隆宏、永田真帆、小泉範子、奥村直毅
    • Industrial Property Rights Holder
      垣塚彰、池田華子、木下茂、中村隆宏、永田真帆、小泉範子、奥村直毅
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 用途特許2018

    • Inventor(s)
      池田華子、畑匡侑
    • Industrial Property Rights Holder
      池田華子、畑匡侑
    • Industrial Property Rights Type
      特許
    • Filing Date
      2018
    • Related Report
      2018 Annual Research Report
    • Overseas

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

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