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The role of galectin-1 in the pathophysiology of ocular disorder

Research Project

Project/Area Number 19K09944
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56060:Ophthalmology-related
Research InstitutionHokkaido University

Principal Investigator

Kanda Atsuhiro  北海道大学, 医学研究院, 客員研究員 (80342707)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsガレクチンー1 / 炎症 / 糖鎖 / 線維化 / 網脈絡膜疾患 / 血管新生
Outline of Research at the Start

これまでに得られたガレクチン-1の血管新生・線維化に関する研究成果をさらに発展させ、網脈絡膜疾患病態の炎症におけるガレクチン-1の病態制御および生理的役割の知見を蓄える。そして、これを基盤とし網脈絡膜疾患に対する新たな分子標的としての治療戦略に確立して、臨床における疾患治療への貢献を目指す。

Outline of Final Research Achievements

We revealed that the glycan-binding protein galectin-1 binds to VEGFR-2 in retinal vascular endothelial cells in a VEGF-independent manner, promotes receptor phosphorylation and cell proliferation, and induces angiogenesis. In diabetic retinopathy, we clarified the mechanism by which IL-1β stimulates the IL-1 receptor in Muller cells and promotes the synthesis of galectin-1 starting from the advanced glycation end products. In this study, we further developed the research results on angiogenesis and fibrosis of galectin-1 obtained so far, and further clarified the pathological control and physiological role of galectin-1 in inflammation of retinal disease pathology.

Academic Significance and Societal Importance of the Research Achievements

現在、眼科領域の分子標的療法では抗VEGF療法が臨床応用されたが、その抗VEGF療法に対して抵抗性を示す症例が多数報告されている。糖鎖結合タンパク質のガレクチン-1はVEGF非依存的に血管新生を眼内で惹起することから、糖鎖および糖鎖結合タンパク質の機能を理解することは糖尿病網膜症や加齢黄斑変性の新たな創薬に繋がる可能性が十分に高い。本研究計画により、眼科創薬が起点となって幅広理分野の研究が活性化され、我が国の医療水準の向上に貢献することが期待される。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report

Research Products

(38 results)

All 2022 2021 2020 2019

All Journal Article (21 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 21 results,  Open Access: 16 results) Presentation (14 results) (of which Int'l Joint Research: 6 results,  Invited: 2 results) Book (3 results)

  • [Journal Article] Downregulation of AlphaB-crystallin in Retinal Pigment Epithelial Cells Exposed to Diabetes- related Stimuli In Vivo and In Vitro.2022

    • Author(s)
      u DI, Kase S, Liu YE, Kanda A, Murata M, Ishida S
    • Journal Title

      In Vivo

      Volume: 36 Pages: 132-139

    • DOI

      10.21873/invivo.12684

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Macrophage-like iPS-derived Suppressor Cells Reduce Th1-mediated Immune Response to a Retinal Antigen.2021

    • Author(s)
      Hase K, Namba K, Wada H, Tsuji H, Maeda A, Murata T, Otsuka R, Iwata D, Kanda A, Noda K, Kitaichi N, Seino KI, Ishida S.
    • Journal Title

      Current Eye Research

      Volume: 46 Pages: 1908-1916

    • DOI

      10.1080/02713683.2021.1952605

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Comparison of clinical characteristics in patients with acute zonal occult outer retinopathy according to anti-retinal antibody status.2021

    • Author(s)
      Hashimoto Y, Saito W, Kanaizumi S, Saito M, Noda K, Kanda A, Ishida S.
    • Journal Title

      Graefes Arch Clin Exp Ophthalmol.

      Volume: 259 Pages: 2967-2976

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of Vascular Endothelial Growth Factor-C in the Trabecular Meshwork of Patients with Neovascular Glaucoma and Primary Open-Angle Glaucoma.2021

    • Author(s)
      Hase K, Kase S, Kanda A, Shinmei Y, Noda K, Ishida S.
    • Journal Title

      J Clin Med.

      Volume: 10 Pages: 2977-2977

    • DOI

      10.3390/jcm10132977

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Hypoxia Induces Galectin-1 Expression Via Autoinduction of Placental Growth Factor in Retinal Pigment Epithelium Cells.2021

    • Author(s)
      Yamamoto T, Kanda A, Kase S, Ishida S.
    • Journal Title

      Invest Ophthalmol Vis Sci

      Volume: 62 Pages: 22-22

    • DOI

      10.1167/iovs.62.2.22

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Acute unilateral inner retinal dysfunction with photophobia: importance of electrodiagnosis2020

    • Author(s)
      Hirakata Toshiaki、Fujinami Kaoru、Saito Wataru、Kanda Atsuhiro、Hirakata Akito、Ishida Susumu、Murakami Akira、Tsunoda Kazushige、Miyake Yozo
    • Journal Title

      Japanese Journal of Ophthalmology

      Volume: 65 Issue: 1 Pages: 42-53

    • DOI

      10.1007/s10384-020-00780-x

    • NAID

      210000164772

    • ISSN
      0021-5155, 1613-2246
    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Receptor-Associated Prorenin System in the Trabecular Meshwork of Patients with Primary Open-Angle Glaucoma and Neovascular Glaucoma2020

    • Author(s)
      Ishizuka Erdal Tan、Kanda Atsuhiro、Shinmei Yasuhiro、Ohguchi Takeshi、Tagawa Yoshiaki、Hase Keitaro、Yamamoto Taku、Noda Kousuke、Chin Shinki、Ishida Susumu
    • Journal Title

      Journal of Clinical Medicine

      Volume: 9 Pages: 2336-2336

    • DOI

      10.3390/jcm9082336

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Divergent Effects of HSP70 Overexpression in Photoreceptors During Inherited Retinal Degeneration2020

    • Author(s)
      Jiang Ke、Fairless Elizabeth、Kanda Atsuhiro、Gotoh Norimoto、Cogliati Tiziana、Li Tiansen、Swaroop Anand
    • Journal Title

      Investigative Opthalmology & Visual Science

      Volume: 61 Pages: 25-25

    • DOI

      10.1167/iovs.61.12.25

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Glucocorticoid‐transactivated TSC22D3 attenuates hypoxia‐ and diabetes‐induced M?ller glial galectin‐1 expression via HIF‐1α destabilization2020

    • Author(s)
      Kanda Atsuhiro、Hirose Ikuyo、Noda Kousuke、Murata Miyuki、Ishida Susumu
    • Journal Title

      Journal of Cellular and Molecular Medicine

      Volume: 24 Pages: 4589-4599

    • DOI

      10.1111/jcmm.15116

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cytoprotective Effect of Astaxanthin in a Model of Normal Intraocular Pressure Glaucoma2020

    • Author(s)
      Kikuchi Kasumi、Dong Zhenyu、Shinmei Yasuhiro、Murata Miyuki、Kanda Atsuhiro、Noda Kosuke、Harada Takayuki、Ishida Susumu
    • Journal Title

      Journal of Ophthalmology

      Volume: 2020 Pages: 1-6

    • DOI

      10.1155/2020/9539681

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Attenuation of experimental autoimmune uveoretinitis in mice by IKKβ inhibitor IMD-03542020

    • Author(s)
      Liu Y, Kitaichi N, Wu D, Hase K, Satoh M, Iwata D, Namba K, Kanda A, Noda K, Itai A, Iwabuchi K, Ishida S
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 525 Pages: 589-594

    • DOI

      10.1016/j.bbrc.2020.02.117

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Blockade of Platelet-Derived Growth Factor Signaling Inhibits Choroidal Neovascularization and Subretinal Fibrosis in Mice2020

    • Author(s)
      Liu Ye、Noda Kousuke、Murata Miyuki、Wu Di、Kanda Atsuhiro、Ishida Susumu
    • Journal Title

      Journal of Clinical Medicine

      Volume: 9 Pages: 2242-2242

    • DOI

      10.3390/jcm9072242

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Non-paraneoplastic autoimmune retinopathy that developed in fellow eye 10?years after onset in first eye: a case report2020

    • Author(s)
      Miura Gen、Baba Takayuki、Iwase Takehito、Ohde Hisao、Kanda Atsuhiro、Saito Wataru、Ishida Susumu、Yamamoto Shuichi
    • Journal Title

      BMC Ophthalmology

      Volume: 20 Pages: 132-132

    • DOI

      10.1186/s12886-020-01414-z

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Involvement of M?ller Glial Autoinduction of TGF-β in Diabetic Fibrovascular Proliferation Via Glial?Mesenchymal Transition2020

    • Author(s)
      Wu Di、Kanda Atsuhiro、Liu Ye、Noda Kousuke、Murata Miyuki、Ishida Susumu
    • Journal Title

      Investigative Opthalmology & Visual Science

      Volume: 61 Pages: 29-29

    • DOI

      10.1167/iovs.61.14.29

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regulation of Spermine Oxidase through Hypoxia-Inducible Factor-1α Signaling in Retinal Glial Cells under Hypoxic Conditions2020

    • Author(s)
      Wu Di、Noda Kousuke、Murata Miyuki、Liu Ye、Kanda Atsuhiro、Ishida Susumu
    • Journal Title

      Investigative Opthalmology & Visual Science

      Volume: 61 Pages: 52-52

    • DOI

      10.1167/iovs.61.6.52

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Increased plasma galectin-1 correlates with advanced glycation end products and interleukin-1 β in patients with proliferative diabetic retinopathy2019

    • Author(s)
      Hase K, Kanda A, Noda K, Ishida S
    • Journal Title

      International Journal of Ophthalmology

      Volume: 12 Pages: 692-694

    • DOI

      10.18240/ijo.2019.04.28

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Glucocorticoid receptor inhibits Muller glial galectin‐1 expression via DUSP1‐dependent and ‐independent deactivation of AP‐1 signalling2019

    • Author(s)
      Hirose Ikuyo, Kanda Atsuhiro, Noda Kousuke, Ishida Susumu
    • Journal Title

      Journal of Cellular and Molecular Medicine

      Volume: 23 Pages: 6785-6796

    • DOI

      10.1111/jcmm.14559

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] (Pro)renin receptor: Involvement in diabetic retinopathy and development of molecular targeted therapy2019

    • Author(s)
      Kanda Atsuhiro, Ishida Susumu
    • Journal Title

      Journal of Diabetes Investigation

      Volume: 10 Pages: 6-17

    • DOI

      10.1111/jdi.12842

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Suppression of choroidal neovascularization and fibrosis by a novel RNAi therapeutic agent against (pro)renin receptor.2019

    • Author(s)
      Liu Y, Kanda A, Wu D, Ishizuka ET, Kase S, Noda K, Ichihara A, Ishida S
    • Journal Title

      Molecular Therapy - Nucleic Acids

      Volume: 17 Pages: 113-125

    • DOI

      10.1016/j.omtn.2019.05.012

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Unsaturated Aldehyde Acrolein Promotes Retinal Glial Cell Migration2019

    • Author(s)
      Murata Miyuki、Noda Kousuke、Yoshida Shiho、Saito Michiyuki、Fujiya Akio、Kanda Atsuhiro、Ishida Susumu
    • Journal Title

      Investigative Opthalmology & Visual Science

      Volume: 60 Pages: 4425-4435

    • DOI

      10.1167/iovs.19-27346

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Galectin-1 promotes choroidal neovascularization and subretinal fibrosis mediated via epithelial-mesenchymal transition2019

    • Author(s)
      Wu Di、Kanda Atsuhiro、Liu Ye、Kase Satoru、Noda Kousuke、Ishida Susumu
    • Journal Title

      FASEB J

      Volume: 33 Pages: 2498-2513

    • DOI

      10.1096/fj.201801227r

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] The close link between hypoxia and autoinduction of placental growth factor in galectin-1 expression in retinal pigment epithelium cells.2021

    • Author(s)
      Yamamoto T, Kanda A, Kase S, Ishida S.
    • Organizer
      Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting(国際学会)
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 網膜色素上皮細胞におけるガレクチン-1発現制御と胎盤成長因子の自己誘導.2021

    • Author(s)
      山本 拓、神田敦宏、加瀬 諭、石田 晋.
    • Organizer
      第125回日本眼科学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] (プロ)レニン受容体を標的にした新規機能阻害薬(核酸医薬)の開発2021

    • Author(s)
      神田敦宏.
    • Organizer
      第40回日本眼薬理学会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] Glucocorticoid-transactivated TSC22D3 attenuates hypoxia- and diabetes-induced Muller glial galectin-1 expression via HIF-1α destabilization2020

    • Author(s)
      Kanda A, Hirose I, Yoshida S, Noda K, Murata M, Ishida S.
    • Organizer
      Euretina 2020 Virtual
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] The vicious cycle of TGF-β autoinduction contributes to VEGF-A expression in Muller glial cells.2020

    • Author(s)
      Wu D, Kanda A, Murata M, Ishida S.
    • Organizer
      Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting: Web
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Dexamethasone attenuates hypoxia- and diabetes-induced retinal galectin-1 expression via reducing hypoxia-inducible factor-1α protein in vitro and in vivo.2020

    • Author(s)
      Kanda A, Hirose I, Yoshida, Murata M, Ishida S.
    • Organizer
      Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting: Web
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] Hypoxia-inducible factor-1α is a key regulator of galectin-1/ LGALS1 expression in human retinal pigment epithelial cells.2020

    • Author(s)
      Yamamoto T, Kanda A, Murata M, Kase S, Ishida S.
    • Organizer
      Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting: Web
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] 血管新生緑内障の病態形成における受容体結合プロレニン系の関与2020

    • Author(s)
      神田敦宏、石塚タンエルダル、新明康弘、大口剛司、陳 進輝、石田 晋.
    • Organizer
      第26回日本糖尿病眼学会総会、Web開催
    • Related Report
      2020 Research-status Report
  • [Presentation] 長期経過観察した抗リカバリン抗体陽性非腫瘍随伴自己免疫性網膜症の1例2020

    • Author(s)
      田中孝幸、安藤 亮、神田敦宏、齋藤 航、石田 晋.
    • Organizer
      第68回日本臨床視覚電気生理学会、Web開催
    • Related Report
      2020 Research-status Report
  • [Presentation] 網膜色素上皮細胞における血管新生因子ガレクチン-1発現制御機構の解明2020

    • Author(s)
      山本 拓、神田敦宏、加瀬 諭、村田美幸、石田 晋.
    • Organizer
      第124回日本眼科学会総会、WEB開催
    • Related Report
      2020 Research-status Report
  • [Presentation] TGF-β causes VEGF-A expression forming the vicious cycle of TGF-β autoinduction.2020

    • Author(s)
      Wu D, Kanda A, Murata M, Ishida S.
    • Organizer
      第124回日本眼科学会総会、WEB開催
    • Related Report
      2020 Research-status Report
  • [Presentation] Mullerグリア細胞における低酸素誘導ガレクチン-1発現の制御機構.2020

    • Author(s)
      神田敦宏.
    • Organizer
      第13回Retina Research Meeting
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] Transcriptional suppression of galectin-1/LGALS1 by glucocorticoids in Muller glial cells and diabetic retinopathy2019

    • Author(s)
      Kanda A, Hirose I, Noda K, Ishida S
    • Organizer
      Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting: Vancouver
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] グルココルチコイドによるガレクチン-1発現制御機構の解明2019

    • Author(s)
      神田敦宏、廣瀬育代、石田 晋
    • Organizer
      第39回日本眼薬理学会
    • Related Report
      2019 Research-status Report
  • [Book] 脈絡膜血管新生と線維化におけるガレクチン-1の関与.2020

    • Author(s)
      呉迪、神田敦宏、石田 晋.
    • Publisher
      北海道医学雑誌.
    • Related Report
      2020 Research-status Report
  • [Book] 糖鎖と糖鎖結合タンパク質の相互作用による糖尿病網膜症病態形成機序の解明.研究報告書2020

    • Author(s)
      神田敦宏.
    • Total Pages
      1
    • Publisher
      日本失明予防協会
    • Related Report
      2020 Research-status Report
  • [Book] 糖尿病最新の治療2019-20212019

    • Author(s)
      門脇 孝、荒木 栄一、綿田 裕孝
    • Total Pages
      348
    • Publisher
      南江堂
    • ISBN
      9784524245567
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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