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development of a novel drug delivery system of calpain

Research Project

Project/Area Number 19K09926
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

Nakazawa Mitsuru  弘前大学, 医学研究科, 名誉教授 (80180272)

Co-Investigator(Kenkyū-buntansha) 阿部 俊明  東北大学, 医学系研究科, 教授 (90191858)
Project Period (FY) 2019-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords網膜色素変性 / カルパイン / 視細胞保護 / 視細胞変性 / ミトコンドリアカルパイン / ペプチド療法 / 視細胞死 / 光干渉断層計 / カルパイン阻害ペプチド / 網膜変性モデルラット
Outline of Research at the Start

本研究は網膜色素変性の新規治療法の開発を最終目的とした研究で、カルパイン阻害ペプチドによって網膜視細胞の変性を少しでも遅らせることができるかどうかを検証するために、ペプチドを徐々に放出できる物質を遺伝性網膜変性ラットの眼球表面の結膜の下に埋植して実際にラットの網膜変性進行が遅れるかどうかを光干渉断層計や光学顕微鏡および電子顕微鏡による形態的および網膜電図による機能的側面から経時的に計測する。

Outline of Final Research Achievements

Since mitochondrial calpain, a type of calpain, activates apoptosis-inducing factor, we hypothesized that suppressing calpain might inhibit photoreceptor cell death to some extent, The results were compared with those of control eyes. In this study, right eyes of six rhodopsin P23H transgenic rats were used as the treated eyes and the left eyes as the control eyes, and the rats were followed up for 3 months. Results showed that there were no significant differences between the two groups in optical coherence tomography, electroretinogram, and fundus photographs for 3 months, and no differences in findings between the two groups in histological examination and transmission electron microscopy findings at 3 months.

Academic Significance and Societal Importance of the Research Achievements

本研究は網膜色素変性という本邦における成人中途視覚障害原因第2位(14%)の疾患に対する治療法開発という意義をもつ。本疾患には現在のところ有効な治療法がなく、遺伝子治療、再生医療および人工視覚などの最先端技術を駆使した治療法が開発されつつあるが、いずれも高額な予算を必要とするため、医療費負担が大きくなると予想される。その点、薬物療法は視細胞保護治療として多くの患者に比較的安価にしかも繰り返し施行できる利点がある。もし、この方法の有効性が確認され、カルパイン阻害を主体とした新規視細胞保護治療法が実用化されれば、本疾患患者への恩恵は計り知れないと確信している。

Report

(5 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (29 results)

All 2022 2021 2020 2019 2018

All Journal Article (19 results) (of which Peer Reviewed: 18 results,  Open Access: 14 results) Presentation (8 results) Book (2 results)

  • [Journal Article] A case of herpes zoster ophthalmicus with optic neuritis of the total length of the optic nerve in the orbital space and ischemic optic neuropathy2022

    • Author(s)
      Takashi Kudo, Kodai Yamauchi, Yukihiko Suzuki, Mitsuru Nakazawa, Shinji Ueno
    • Journal Title

      American Journal of Ophthalmology Case Reports

      Volume: 28 Pages: 101756-101756

    • DOI

      10.1016/j.ajoc.2022.101756

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of surgeon-related factors on outcome of retinal detachment surgery: analyses of data in Japan-retinal detachment registry2022

    • Author(s)
      Yamakiri K, Sakamoto T, Koriyama C, Kawasaki R, Baba T, Nishitsuka K, Koto T, Terasaki H; Japan Retinal Detachment Registry
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 4213-4213

    • DOI

      10.1038/s41598-022-07838-5

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Six-months primary success rate for retinal detachment between vitrectomy and scleral buckling2021

    • Author(s)
      Koto T, Kawasaki R, Yamakiri K, Baba T, Nishitsuka N, Hirakata A, Sakamoto T, for the Japan-Retinal Detachment Resistry Group
    • Journal Title

      Retina

      Volume: 41 Pages: 1164-1173

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] A case of cyclodialysis after microhook trabelotomy treated with vitreous surgery2021

    • Author(s)
      Kudo T, Suzuki Y, Yamauchi K, Tando T, Adachi K, Nakazawa M
    • Journal Title

      Case Reports in Ophthalmology

      Volume: 12 Issue: 1 Pages: 83-91

    • DOI

      10.1159/000510756

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Racemose hemangioma complicated with macular microaneurysm rupture2021

    • Author(s)
      Yamauchi K, Suzuki Y, Tanaka-Gonome T, Adachi K, Maeda N, Nakazawa M
    • Journal Title

      American Journal of Ophthalmology Case Reports

      Volume: 22 Pages: 101053-101053

    • DOI

      10.1016/j.ajoc.2021.101053

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Scleral buckling versus pars plana vitrectomy in simple phakic macula-on retinal detachment: a propensity score-matched, registry-based study.2021

    • Author(s)
      Kawano Sumihiro, Imai Takumi. Sakamoto Taiji, Japan-Retinal Detachment Registry Group.
    • Journal Title

      British Journal of Ophthalmology

      Volume: bjophthalmol-2020-318451 Issue: 6 Pages: 2020-318451

    • DOI

      10.1136/bjophthalmol-2020-318451

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Regional and sex differences in retinal detachment surgery: Japan-retinal detachment registry report2021

    • Author(s)
      Funatsu Ryoh、Terasaki Hiroto、Sakamoto Taiji、the Japan Retinal Detachment Registry study group
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 20611-20611

    • DOI

      10.1038/s41598-021-00186-w

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 緑内障治療中に強い角膜混濁を生じた1例2021

    • Author(s)
      中澤 満、原 藍子
    • Journal Title

      臨床眼科

      Volume: 75 Pages: 1282-1285

    • Related Report
      2021 Research-status Report
  • [Journal Article] Intraoperative choroidal detachment occurring in a case of perforating ocular injury.2020

    • Author(s)
      Suzuki Y, Suzuki K, Tanabu R, Maeda N, Nakazawa M
    • Journal Title

      American journal of Ophthalmology Case Reports

      Volume: 18 Pages: 100643-100643

    • DOI

      10.1016/j.ajoc.2020.100643

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A spectral-domain optical coherence tomographic analysis of RDH5-/- mice retina.2020

    • Author(s)
      Xie Y, Gonome T, Yamauchi K, Maeda-Monai N, Tanabu R, Ishiguro S-I, Nakazawa M
    • Journal Title

      PLOS ONE

      Volume: 15 Issue: 4 Pages: e0231220-e0231220

    • DOI

      10.1371/journal.pone.0231220

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Modified intraocular lens intrascleral fixation technique using two vitrectomy ports as lens haptic fixation sites.2020

    • Author(s)
      Suzuki Y, Tando T, Adachi K, Kudo T, Nakazawa M
    • Journal Title

      Clinical Ophthalmology

      Volume: 14 Pages: 1223-1228

    • DOI

      10.2147/opth.s247920

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The qualitative assessment of optical coherence tomography and the central retinal sensitivity in patients with retinitis pigmentosa.2020

    • Author(s)
      Hara A, Nakazawa M, Saito M, Suzuki Y
    • Journal Title

      PLOS ONE

      Volume: 15 Issue: 5 Pages: e0232700-e0232700

    • DOI

      10.1371/journal.pone.0232700

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Proliferative diabetic retinopathy without preoperative pan-retinal photocoagulation is associated with higher levels of intravitreal IL-6 and postoperative inflammation2020

    • Author(s)
      Suzuki Y, Adachi K, Maeda N, Tanabu R, Kudo T, Nakazawa M
    • Journal Title

      International Journal of Retina and Vitreous

      Volume: 6 Issue: 1 Pages: 24-24

    • DOI

      10.1186/s40942-020-00222-3

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The protective effect of astaxanthin on the ganglion cell complex in glutamate/aspartate transporter deficient mice, a model of normal tension glaucoma, analyzed by spectral-domain optical coherence tomography2020

    • Author(s)
      Tanaka-Gonome T, Xie Y, Yamauchi K, Maeda-Monai N, Tanabu R, Kudo T, Nakazawa M
    • Journal Title

      Biochemistry and Biophysics Reports

      Volume: 2020 Pages: 100777-100777

    • DOI

      10.1016/j.bbrep.2020.100777

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Serum anti-recoverin antibodies is found in elderly patients with retinitis pigmentosa and cancer2020

    • Author(s)
      Sato T, Nishiguchi K M, Fujita K, Miya F, Inoue T, Sasaki E, Asano T, Tsuda S, Shiga Y, Kunikata H, Nakazawa M, Nakazawa T
    • Journal Title

      Acta Ophthalmologica

      Volume: 98 Issue: 6

    • DOI

      10.1111/aos.14373

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] N-methyl-N-nitrosourea-induced photoreceptor degeneration is inhibited by nicotinamide via the blockade of upstream events before the phosphorylation of signaling proteins.2019

    • Author(s)
      Sugano E, Tabata K, Takezawa T, Shiraiwa R, Muraoka H, Metoki T, Kudo A, Nakazawa M, Tomita H, Iwama Y
    • Journal Title

      BioMed Research International

      Volume: 2019 Pages: 1-10

    • DOI

      10.1155/2019/3238719

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Phenotypic features of Oguchi disease and retinitis pigmentosa in patients with SAG mutations. A long-term follow-up study2019

    • Author(s)
      Nishiguchi KM, Ikeda Y, Fujita K, Kunikata H, Akiho M, Hashimoto K, Hosono K, Kurata K, Koyanagi Y, Akiyama M, Suzuki T, Kawasaki R, Wada Y, Hotta Y, Sonoda K-H, Murakami A, Nakazawa M, Nakazawa T, Abe T.
    • Journal Title

      Ophthalmology

      Volume: 126 Issue: 11 Pages: 1557-1565

    • DOI

      10.1016/j.ophtha.2019.05.027

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Excess glutamate may cause dilation of retinal blood vessels in glutamate/aspartate transporter-deficient mice2019

    • Author(s)
      Gonome T, Xie Y, Arai S, Yamauchi K, Maeda-Monai N, Tanabu R, Kudo T, Nakazawa M
    • Journal Title

      BioMed Research International

      Volume: 2019 Pages: 1-11

    • DOI

      10.1155/2019/6512195

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The findings of optical coherence tomography of retinal degeneration in relation to the morphological and electroretinographic features in RPE65-/- mice2018

    • Author(s)
      Tanabu R, Sato K, Monai N, Yamauchi K, Gonome T, Xie Y, Takahashi S, Ishiguro S, Nakazawa M
    • Journal Title

      PLOS ONE

      Volume: 14 Issue: 1 Pages: e0210439-e0210439

    • DOI

      10.1371/journal.pone.0210439

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 網膜色素変性患者のOCTによる形態パラメータと視野感度指標との関連性2020

    • Author(s)
      原 藍子、齋藤昌晃、鈴木幸彦、中澤 満
    • Organizer
      第124回日本眼科学会
    • Related Report
      2020 Research-status Report
  • [Presentation] 巨細胞性動脈炎による動脈炎性前部虚血性視神経症の1例2020

    • Author(s)
      安達功武、工藤朝香、工藤孝志、毛内奈津姫、鈴木幸彦、中澤 満
    • Organizer
      第74回日本臨床眼科学会
    • Related Report
      2020 Research-status Report
  • [Presentation] 加齢黄斑変性の病型と血小板凝集能を含む血液学的検査結果との関連性2020

    • Author(s)
      鈴木幸彦、齋藤昌晃、安達功武、工藤孝志、中澤 満
    • Organizer
      第59回日本網膜硝子体学会
    • Related Report
      2020 Research-status Report
  • [Presentation] 長期経過で網膜異常血管に多彩な変化がみられた網膜つた状血管腫の1例2020

    • Author(s)
      山内宏大、鈴木幸彦、田中孝幸、安達功武、前田奈津姫、中澤 満
    • Organizer
      第59回日本網膜硝子体学会
    • Related Report
      2020 Research-status Report
  • [Presentation] Optical coherence tomographic analysis of RDH5 knockout mice retina2019

    • Author(s)
      Xie Yuting、中澤 満、山内宏大、毛内奈津姫、田名部玲子、江目孝幸
    • Organizer
      第123回日本眼科学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 硝子体手術用ポートを利用した眼内レンズ強膜内固定法2019

    • Author(s)
      鈴木幸彦、安達功武、毛内奈津姫、田名部玲子、鈴木 香、工藤孝志、中澤 満
    • Organizer
      第123回日本眼科学会
    • Related Report
      2019 Research-status Report
  • [Presentation] 各種網膜変性モデルでのOCT所見、網膜電図および視細胞形態の関連性2019

    • Author(s)
      中澤 満、安達功武、髙橋 静、毛内奈津姫、山内宏大、田名部玲子、江目孝幸、Xie Yuting、石黒誠一、佐藤孝太
    • Organizer
      第123回日本眼科学会
    • Related Report
      2019 Research-status Report
  • [Presentation] GLASTノックアウトマウスの網膜各層厚の経時変化2019

    • Author(s)
      江目孝幸、山内宏大、田名部玲子、毛内奈津姫、Xie Yuting、中澤 満
    • Organizer
      第123回日本眼科学会
    • Related Report
      2019 Research-status Report
  • [Book] 脳回状脈絡網膜萎縮症、後眼部アトラス2019

    • Author(s)
      中澤 満
    • Publisher
      総合医学
    • Related Report
      2019 Research-status Report
  • [Book] 網膜色素変性、嚢胞用黄斑浮腫、メディカル眼科治療アップデート2019

    • Author(s)
      安達功武、中澤 満
    • Publisher
      医学書院
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2024-01-30  

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