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Biochemical study of molecular target therapy for retinal ganglion cell death in glaucoma

Research Project

Project/Area Number 25861611
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Ophthalmology
Research InstitutionHirosaki University

Principal Investigator

Ozaki Taku  弘前大学, 医学(系)研究科(研究院), 特任助教 (70621069)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Keywords緑内障 / 網膜 / 網膜神経節細胞 / アポトーシス / ペプチド医薬 / ミトコンドリア / カルパイン / アポトーシス誘導因子 / ペプチド / 正常眼内緑内障 / グルタミン酸輸送体 / 虚血・再灌流 / アポトーシス誘導因子 AIF / 細胞死 / 正常眼圧緑内障 / グルタミン酸輸送体欠損マウス / GLAST KO マウス
Outline of Final Research Achievements

Glaucoma is a disease that damages the eye's optic nerve and retinal ganglion cells (RGC), resulting in vision loss and blindness. The purpose of the present study was to determine whether the inhibition of mitochondrial μ-calpain protects the RGC in one of the animal models of glaucoma.
I used a well-established rat model of experimental acute glaucoma, ischemia/reperfusion injury. The specific peptide inhibitor of mitochondrial μ-calpain, Tat-μCL, was used for the topical eye-drop application. I applied eye-drops containing 1 mM Tat-μCL to rats three times a day for 5 days after I/R. RGC death was determined by TUNEL assay. The change of retinal function was examined by electroretinogram (ERG).
Eye-drop application of Tat-μCL significantly prevented the RGC death. The Tat-μCL significantly inhibited the decrease of RGC. In addition, both a- and b-wave in ERG were attenuated after I/R, but the eye-drop application of Tat-μCL significantly recovered the attenuation.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (25 results)

All 2015 2014 2013

All Journal Article (9 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 9 results,  Open Access: 5 results,  Acknowledgement Compliant: 4 results) Presentation (16 results) (of which Invited: 1 results)

  • [Journal Article] Delivery of Topically Applied Calpain Inhibitory Peptide to the Posterior Segment of the Rat Eye.2015

    • Author(s)
      Taku Ozaki, Mitsuru Nakazawa, Tetsuro Yamashita, Sei-ichi Ishiguro
    • Journal Title

      PLoS ONE

      Volume: 10 Issue: 6 Pages: e0130986-e0130986

    • DOI

      10.1371/journal.pone.0130986

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Emerging functional cross-talk between the Keap1-Nrf2 system and mitochondria2015

    • Author(s)
      Itoh K, Ye P, Matsumiya T, Tanji K, Ozaki T.
    • Journal Title

      Journal of Clinical Biochemistry and Nutrition

      Volume: 56 Issue: 2 Pages: 91-97

    • DOI

      10.3164/jcbn.14-134

    • NAID

      130004879384

    • ISSN
      0912-0009, 1880-5086
    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Protection of cone photoreceptor M-opsin degeneration with 9-cis-β-carotene rich alga Dunaliella bardawil in Rpe65-/- mouse retinal explant culture.2014

    • Author(s)
      Ozaki T, Nakazawa M, Kudo T, Hirano S, Suzuki K, Ishiguro S
    • Journal Title

      Current Eye Research

      Volume: 39 Issue: 12 Pages: 1221-1231

    • DOI

      10.3109/02713683.2014.907430

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Phosphorylation of serine 349 of p62 in Alzheimer’s disease brain2014

    • Author(s)
      Tanji K, Miki Y, Ozaki T, Maruyama A, Yoshida H, Mimura J, Matsumiya T, Mori F, Imaizumi T, Itoh K, Kakita A, Takahashi H, Wakabayashi K
    • Journal Title

      Acta Neuropathol Comm

      Volume: 2 Issue: 1 Pages: 50-50

    • DOI

      10.1186/2051-5960-2-50

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Restoration of the majority of the visual spectrum by using modified Volvox channelrhodopsin-1.2014

    • Author(s)
      Tomita H, Sugano E, Murayama N, Ozaki T, Nishiyama F, Tabata K, Takahashi M, Saito T, Tamai M.
    • Journal Title

      Mol. Ther.

      Volume: 22(8) Issue: 8 Pages: 1434-1440

    • DOI

      10.1038/mt.2014.81

    • NAID

      120007179833

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Periosteum-derived cells respond to mechanical stretch and activate Wnt and BMP signaling pathways.2014

    • Author(s)
      Ito R, Matsumiya T, Kon T, Narita N, Kubota K, Sakaki H, Ozaki T, Imaizumi T, Kobayashi W, Kimura H.
    • Journal Title

      Biomed Res

      Volume: 35 Pages: 69-79

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Decrease of ATP by mitochondrial m-calpain inhibitory peptide in the rat retinas.2013

    • Author(s)
      Ozaki T, Nakazawa M, Yamashita T, Tomita H, Ebina Y, Ishiguro S.
    • Journal Title

      Cell Struct Funct

      Volume: 38 Pages: 207-223

    • NAID

      130004053897

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Inhibitory peptide of mitochondrial μ-calpain protects against photoreceptor degeneration in rhodopsin transgenic S334ter and P23H rats.2013

    • Author(s)
      Ozaki T, Ishiguro S, Hirano S, Baba A, Yamashita T, Tomita H, Nakazawa M.
    • Journal Title

      PLoS One.

      Volume: 8(8) Issue: 8 Pages: e71650-e71650

    • DOI

      10.1371/journal.pone.0071650

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cisplatin binding and inactivation of mitochondrial glutamate oxaloacetate transaminase in cisplatin-induced rat nephrotoxicity.2013

    • Author(s)
      Ozaki T, Ishiguro S, Itoh H, Furuhama K, Nakazawa M, Yamashita T.
    • Journal Title

      Biosci Biotechnol Biochem

      Volume: 77 Pages: 1645-1649

    • NAID

      10031195811

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 各種網膜硝子体疾患の硝子体中抗酸化力の検討2014

    • Author(s)
      中澤 満、鈴木幸彦、前野敦子、尾﨑 拓、萩原悠介、照井 藍、安達功武、高橋 静、横井由美子
    • Organizer
      第68回日本臨床眼科学会
    • Place of Presentation
      神戸ポートピアホテル
    • Year and Date
      2014-11-13 – 2014-11-16
    • Related Report
      2014 Research-status Report
  • [Presentation] ミトコンドリア・カルパイン-1阻害デコイペプチド点眼のウサギ網膜への送達2014

    • Author(s)
      中澤 満、尾﨑 拓、目時友美、安達功武、高橋 静、石黒誠一、山下哲郎
    • Organizer
      第34回日本眼薬理学会
    • Place of Presentation
      長良川国際会議場
    • Year and Date
      2014-09-13 – 2014-09-14
    • Related Report
      2014 Research-status Report
  • [Presentation] 改変型チャネルロドプシン遺伝子を導入したラットの視機能評価2014

    • Author(s)
      西山史郎、冨田浩史、菅野江里子、村山奈美枝、尾﨑 拓、田端希多子、高橋麻紀、齋藤健彦、玉井信
    • Organizer
      日本動物学会第85回仙台大会
    • Place of Presentation
      東北大学川内北キャンパス
    • Year and Date
      2014-09-11 – 2014-09-13
    • Related Report
      2014 Research-status Report
  • [Presentation] 行動解析による視覚機能評価法の確立2014

    • Author(s)
      西山史郎、冨田浩史、菅野江里子、村山奈美枝、尾﨑 拓、田端希多子、高橋麻紀、齋藤健彦、玉井信
    • Organizer
      日本動物学会平成26年度東北支部会
    • Place of Presentation
      岩手大学復興記念銀河ホール
    • Year and Date
      2014-07-12 – 2014-07-13
    • Related Report
      2014 Research-status Report
  • [Presentation] Delivery of topically applied mitochondrial calpain-1 inhibitory peptide to the rodent retina2014

    • Author(s)
      Mitsuru Nakazawa, Taku Ozaki, Takato Ueno, Sei-ichi Ishiguro, Tetsuro Yamashita
    • Organizer
      World Ophthalmology Congress 2014
    • Place of Presentation
      東京国際フォーラム
    • Year and Date
      2014-04-02 – 2014-04-06
    • Related Report
      2014 Research-status Report
  • [Presentation] Delivery of topically applied mitochondrial μ-calpain inhibitory peptide to the retina2013

    • Author(s)
      Mitsuru Nakazawa, Taku Ozaki, Takato Ueno, Sei-ichi Ishiguro, Tetsuro Yamashita
    • Organizer
      The 8th Congress of Asia-Pacific Vitreo-Retina Society Congress & The 52nd Annual meeting of Japanese Retina and Vitreous Society
    • Place of Presentation
      Nagoya Congress Center
    • Related Report
      2013 Research-status Report
  • [Presentation] ERp57 and GRP75 associate with mitochondrial calpains and modulate AIF-dependent apoptotic pathways in the ocular diseases.2013

    • Author(s)
      Taku Ozaki, Tetsuro Yamashita, Mitsuru Nakazawa, Sei-ichi Ishiguro
    • Organizer
      国際ミニシンポジウム Protein Folding and Disease
    • Place of Presentation
      秋田ビューホテル
    • Related Report
      2013 Research-status Report
  • [Presentation] ミトコンドリアカルパインの発見から眼疾患の治療へ向けて2013

    • Author(s)
      尾﨑 拓
    • Organizer
      第14回 日本農芸化学会東北支部若手シンポジウム
    • Place of Presentation
      繋温泉 清温荘(岩手県盛岡市)
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 網膜視細胞変性を抑制するペプチドの点眼による網膜への送達経路2013

    • Author(s)
      上野嵩登, 尾﨑 拓, 中澤 満, 山下哲郎, 石黒誠一
    • Organizer
      日本動物学会 第84回岡山大会
    • Place of Presentation
      岡山大学 津島キャンパス
    • Related Report
      2013 Research-status Report
  • [Presentation] ミトコンドリアμ-カルパイン阻害による虚血性網膜神経節細胞死の保護2013

    • Author(s)
      尾﨑 拓、石黒誠一、伊藤 優、山下哲郎、中澤 満
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      パシフィコ横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] 9シスβカロテン高含有ドナリエラ・バーダウィルのRPE65-/-マウス錐体オプシン保護作用2013

    • Author(s)
      工藤孝志、尾﨑 拓、中澤 満
    • Organizer
      第124回青森県眼科集談会
    • Place of Presentation
      弘前大学医学部コミュニケーションセンター
    • Related Report
      2013 Research-status Report
  • [Presentation] 網膜色素変性モデルラットの視細胞変性に対するカルパイン阻害ペプチドの保護効果2013

    • Author(s)
      中澤 満、尾﨑 拓、川村英治、石黒誠一、山下哲郎
    • Organizer
      第124回青森県眼科集談会
    • Place of Presentation
      弘前大学医学部コミュニケーションセンター
    • Related Report
      2013 Research-status Report
  • [Presentation] カルパイン阻害ペプチドによる虚血性神経節細胞死の保護2013

    • Author(s)
      尾﨑 拓、石黒誠一、伊藤 優、山下哲郎、中澤 満
    • Organizer
      第124回青森県眼科集談会
    • Place of Presentation
      弘前大学医学部コミュニケーションセンター
    • Related Report
      2013 Research-status Report
  • [Presentation] 9シスβカロテン高含有ドナリエラ・バーダウィルのRPE65-/-マウス錐体オプシン保護作用2013

    • Author(s)
      工藤孝志、尾﨑 拓、中澤 満
    • Organizer
      第117回日本眼科学会総会
    • Place of Presentation
      東京国際フォーラム
    • Related Report
      2013 Research-status Report
  • [Presentation] 網膜色素変性モデルラットの視細胞変性に対するカルパイン阻害ペプチドの保護効果2013

    • Author(s)
      中澤 満、尾﨑 拓、川村英治、石黒誠一、山下哲郎
    • Organizer
      第117回日本眼科学会総会
    • Place of Presentation
      東京国際フォーラム
    • Related Report
      2013 Research-status Report
  • [Presentation] ミトコンドリアm-カルパイン阻害ペプチドによる網膜電図応答の抑制2013

    • Author(s)
      尾﨑 拓、中澤 満、蝦名祐一、石黒誠一、山下哲郎
    • Organizer
      第117回日本眼科学会総会
    • Place of Presentation
      東京国際フォーラム
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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