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Roles for the TRPVs channels in the lens in the initiation of presbyopia

Research Project

Project/Area Number 20K07184
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 47060:Clinical pharmacy-related
Research InstitutionKeio University

Principal Investigator

Nakazawa Yosuke  慶應義塾大学, 薬学部(芝共立), 講師 (60411708)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords老視 / 老眼 / aging / 水晶体 / TRPVチャネル / 白内障病型 / 温度 / 白内障 / 老視(老眼)
Outline of Research at the Start

老眼(老視)は一般的に40歳-50歳から発症し、100%の罹患率をもつ眼疾患である。根本的な治療法はなく、近距離作業の際は老眼鏡などを用いて見えにくさを補っている。日本がこれから直面する“超高齢化社会”において、白内障/老眼患者は増加することが容易に予想され、老眼基礎研究・抗老眼薬の開発は重要な課題である。白内障は世界失明原因の第一位であるため、世界中で抗白内障薬の探索が盛んに行われているが、申請者は老眼の抑制が、白内障発症遅延を引き起こし、世界の失明から守ると推察している。
本研究により老眼基礎研究の飛躍的向上と、抗老眼薬の開発の基盤を作り、明るい視野と健康な老後生活に貢献する。

Outline of Final Research Achievements

In this study, we examined the function of TRPV channels in the lens and contribution for presbyopia onset. We have previously reported the localization of TRPV channels in the lens, and examined the factors that influence their localization in this study. As a result, we found that the localization was changed by changes in external temperature and stimulation pressure from the ciliary muscle. We also found that administration of the anti-cataract candidate compounds hesperetin and water-soluble hesperidin suppressed the decrease in elasticity of the mouse lens due to altering the localization of TRPV channels. Furthermore, we found that Capsaicin, which is TRPV1 agonist, eye drops suppressed the development of secondary cataracts. In the future, we will examine TRPV channels in human lens samples and create the basis for the development of anti-presbyopia drugs.

Academic Significance and Societal Importance of the Research Achievements

老視の世界人口は年々増加しており、2030年には人口の25%が老視に悩まされると推察されている。また我が国日本においても高齢者雇用安定法が改正・施行されたとから、高齢者の視機能はますます重要な課題となってくる。さらに“健康日本21プロジェクト”で掲げている健康寿命延命に向けても視機能の維持は欠かせない。
本研究遂行により、水晶体のTRPVチャネルの役割が明らかとなりまた、老視モデル動物の基盤を作ることができた。2023年現在、日本で老視に適応可能な医薬品は存在しない。本研究が基盤となり、モデル動物が開発されれば、老視薬物治療開発が飛躍的に伸び、健康寿命の延伸に大きく貢献できると確信している。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (25 results)

All 2023 2022 2021 2020 Other

All Int'l Joint Research (4 results) Journal Article (10 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 10 results,  Open Access: 10 results) Presentation (11 results) (of which Invited: 4 results)

  • [Int'l Joint Research] NIPER-Ahmedabad, Gujarat(インド)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] The Univerisity of Auckland(ニュージーランド)

    • Related Report
      2022 Annual Research Report
  • [Int'l Joint Research] The University of Auckland(ニュージーランド)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] University of California, Irvine(米国)

    • Related Report
      2021 Research-status Report
  • [Journal Article] Hesperetin treatment attenuates glycation of lens proteins and advanced?glycation end products generation2023

    • Author(s)
      Doki Yuri、Nakazawa Yosuke、Morishita Naoki、Endo Shin、Nagai Noriaki、Yamamoto Naoki、Tamura Hiroomi、Funakoshi?Tago Megumi
    • Journal Title

      Molecular Medicine Reports

      Volume: 27 Issue: 5 Pages: 12990-12990

    • DOI

      10.3892/mmr.2023.12990

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Oral Formulation Based on Irbesartan Nanocrystals Improve Drug Solubility, Absorbability, and Efficacy2022

    • Author(s)
      Nagai Noriaki、Ogata Fumihiko、Ike Ayari、Shimomae Yurisa、Osako Hanano、Nakazawa Yosuke、Yamamoto Naoki、Kawasaki Naohito
    • Journal Title

      Pharmaceutics

      Volume: 14 Issue: 2 Pages: 387-387

    • DOI

      10.3390/pharmaceutics14020387

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Novel Mechanism by a Bis-Pyridinium Fullerene Derivative to Induce Apoptosis by Enhancing the MEK-ERK Pathway in a Reactive Oxygen Species-Independent Manner in BCR-ABL-Positive Chronic Myeloid Leukemia-Derived K562 Cells.2022

    • Author(s)
      Sumi K, Tago K, Nakazawa Y, Takahashi K, Ohe T, Mashino T, Funakoshi-Tago M
    • Journal Title

      Int J Mol Sci.

      Volume: 23(2) Issue: 2 Pages: 749-749

    • DOI

      10.3390/ijms23020749

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A bis-pyridinium fullerene derivative induces apoptosis through the generation of ROS in BCR-ABL-positive leukemia cells.2022

    • Author(s)
      Sumi K, Tago K, Nakazawa Y, Takahashi K, Ohe T, Mashino T, Funakoshi-Tago M
    • Journal Title

      Eur J Pharmacol.

      Volume: 916 Pages: 174714-174714

    • DOI

      10.1016/j.ejphar.2021.174714

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Capsaicin attenuates TGFβ2-induced epithelial-mesenchymal-transition in lens epithelial cells in vivo and in vitro2021

    • Author(s)
      Sugiyama Yuki、Nakazawa Yosuke、Sakagami Toko、Kawata Sara、Nagai Noriaki、Yamamoto Naoki、Funakoshi-Tago Megumi、Tamura Hiroomi
    • Journal Title

      Experimental Eye Research

      Volume: 213 Pages: 108840-108840

    • DOI

      10.1016/j.exer.2021.108840

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regulation of the Membrane Trafficking of the Mechanosensitive Ion Channels TRPV1 and TRPV4 by Zonular Tension, Osmotic Stress and Activators in the Mouse Lens2021

    • Author(s)
      Nakazawa Yosuke、Petrova Rosica S.、Sugiyama Yuki、Nagai Noriaki、Tamura Hiroomi、Donaldson Paul J.
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 23 Pages: 12658-12658

    • DOI

      10.3390/ijms222312658

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Differences in a Single Extracellular Residue Underlie Adhesive Functions of Two Zebrafish Aqp0s2021

    • Author(s)
      Vorontsova Irene、Hall James E.、Schilling Thomas F.、Nagai Noriaki、Nakazawa Yosuke
    • Journal Title

      Cells

      Volume: 10 Issue: 8 Pages: 2005-2005

    • DOI

      10.3390/cells10082005

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Prevention of Postprandial Hyperglycemia by Ophthalmic Nanoparticles Based on Protamine Zinc Insulin in the Rabbit2021

    • Author(s)
      Deguchi Saori、Ogata Fumihiko、Isaka Takumi、Otake Hiroko、Nakazawa Yosuke、Kawasaki Naohito、Nagai Noriaki
    • Journal Title

      Pharmaceutics

      Volume: 13 Issue: 3 Pages: 375-375

    • DOI

      10.3390/pharmaceutics13030375

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of Alpha-Glucosyl-Hesperidin Consumption on Lens Sclerosis and Presbyopia2021

    • Author(s)
      Nakazawa Yosuke、Doki Yuri、Sugiyama Yuki、Kobayashi Ryota、Nagai Noriaki、Morisita Naoki、Endo Shin、Funakoshi-Tago Megumi、Tamura Hiroomi
    • Journal Title

      Cells

      Volume: 10 Issue: 2 Pages: 382-382

    • DOI

      10.3390/cells10020382

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Oral consumption of α-glucosyl-hesperidin could prevent lens hardening, which causes presbyopia2021

    • Author(s)
      Nakazawa Yosuke、Aoki Miki、Doki Yuri、Morishita Naoki、Endo Shin、Nagai Noriaki、Funakoshi-Tago Megumi、Tamura Hiroomi
    • Journal Title

      Biochemistry and Biophysics Reports

      Volume: 25 Pages: 100885-100885

    • DOI

      10.1016/j.bbrep.2020.100885

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 老視薬物治療の現状と問題2023

    • Author(s)
      中澤洋介
    • Organizer
      第一回 日本老視学会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 水晶体のチャネル研究と老眼モデル動物の作製2023

    • Author(s)
      中澤洋介
    • Organizer
      第1回 眼科創薬研究会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 高温環境での核白内障発症におけるTRPVチャネルの関与2022

    • Author(s)
      中澤洋介、嶋田響、工野由美香、多胡めぐみ、平松範子、山本直樹、長井紀章、武田駿、永田万由美、佐々木洋
    • Organizer
      第61回 日本白内障学会 / 第48回水晶体研究会
    • Related Report
      2022 Annual Research Report
  • [Presentation] TRPV チャネルを介した EMT 抑制メカニズムの解析2022

    • Author(s)
      中澤 洋介、杉山 裕紀、河田 沙礼、長井 紀章、山本 直樹、 Petrova Rosica、Donaldson Paul、多胡めぐみ
    • Organizer
      第42回 日本眼薬理学会
    • Related Report
      2022 Annual Research Report
  • [Presentation] TRPVチャネルの活性化は、後発白内障を抑制する2021

    • Author(s)
      中澤洋介、杉山裕紀、阪上瞳子、河田沙良、長井紀章、山本直樹、多胡めぐみ、田村悦臣
    • Organizer
      第60回日本白内障学会総会/第47回水晶体研究会
    • Related Report
      2021 Research-status Report
  • [Presentation] イオンチャネルのDiscuvery2021

    • Author(s)
      中澤洋介
    • Organizer
      第60回日本白内障学会総会/第47回水晶体研究会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 温度の違いがヒト水晶体中ミトコンドリア機能へ及ぼす影響:高環境温度はエーティーピーの過剰産生を誘発する2021

    • Author(s)
      長井紀章、武田峻、出口粧央里、山本直樹、中澤洋介、高田匠、宮田佳樹、平松範子、永田万由美、久保江理、佐々木洋
    • Organizer
      第60回日本白内障学会総会/第47回水晶体研究会
    • Related Report
      2021 Research-status Report
  • [Presentation] 水晶体タンパク質の糖化抑制を介したヘスペレチンの抗老視および抗白内障効果2021

    • Author(s)
      土岐 友理、中澤 洋介、森下 尚紀、遠藤 伸、多胡 めぐみ、田村 悦臣
    • Organizer
      第68回 日本食品科学工学会
    • Related Report
      2021 Research-status Report
  • [Presentation] α-グルコシルヘスペリジンの経口摂取は、老眼の発症を抑制する。2021

    • Author(s)
      中澤 洋介、土岐 友理、杉山 裕紀、森下 尚紀、遠藤 伸、田村 悦臣、多胡 めぐみ
    • Organizer
      第68回 日本食品科学工学会
    • Related Report
      2021 Research-status Report
  • [Presentation] トウガラシ含有成分Capsaicinを介したTRPV1活性化による後発白内障への影響2021

    • Author(s)
      杉山 裕紀、河田 沙礼、阪上 瞳子、中澤 洋介、田村 悦臣、多胡 めぐみ
    • Organizer
      第68回 日本食品科学工学会
    • Related Report
      2021 Research-status Report
  • [Presentation] alpha-glucosyl hesperidinの白内障予防効果の検討2020

    • Author(s)
      中澤洋介
    • Organizer
      第12回ヘスペリジン研究会
    • Related Report
      2020 Research-status Report
    • Invited

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Published: 2020-04-28   Modified: 2024-01-30  

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