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Development of Rho kinase inhibitor eye drop as the therapy for treating corneal endothelial dysfunction

Research Project

Project/Area Number 25861660
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Ophthalmology
Research InstitutionDoshisha University

Principal Investigator

OKUMURA Naoki  同志社大学, 生命医科学部, 助教 (10581499)

Project Period (FY) 2013-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords角膜内皮 / Rhoキナーゼ / Rhoキナーゼ阻害剤 / アポトーシス / ROCK阻害剤
Outline of Final Research Achievements

Human corneal endothelial cells (HCECs) are known to have poor regenerative ability, and non-compensatory damage of those cells causes irreversible corneal haziness. Although corneal transplantations provide considerable clinical benefits, allograft rejection, primary graft failure, and the worldwide shortage of donor corneas are associated problems that have yet to be overcome. Since the development of new therapies is the key to solving these problems, we have attempted to establish a new clinical intervention for the treatment of corneal endothelial dysfunction. In this research, we investigate the mechanism by which ROCK inhibitor suppresses apoptosis. We demonstrated that ROCK inhibitor suppresses apoptosis by suppressing cell detachment from the substrate via inhibiting MLC phosphorylation, and that it could be further developed as a therapeutic agent to modulate CEC apoptosis.

Report

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

    (32 results)

All 2014 2013 Other

All Journal Article (10 results) (of which Peer Reviewed: 8 results) Presentation (20 results) (of which Invited: 3 results) Remarks (2 results)

  • [Journal Article] New therapeutic modality for corneal endothelial disease using Rho-associated kinase inhibitor eye drops.2014

    • Author(s)
      Koizumi N, Okumura N, Ueno M, Kinoshita S
    • Journal Title

      Cornea

      Volume: 33 Issue: Supplement 11 Pages: S25-S31

    • DOI

      10.1097/ico.0000000000000240

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Cell-based approach for treatment of corneal endothelial dysfunction.2014

    • Author(s)
      Okumura N, Kinoshita S, Koizumi N
    • Journal Title

      Cornea

      Volume: 33 Issue: Supplement 11 Pages: S37-S41

    • DOI

      10.1097/ico.0000000000000229

    • Related Report
      2014 Annual Research Report
  • [Journal Article] Involvement of cyclin D and p27 in cell proliferation mediated by ROCK inhibitors Y-27632 and Y-39983 during corneal endothelium wound healing.2014

    • Author(s)
      Okumura N, Nakano S, Kay EP, Numata R, Ota A, Sowa Y, Sakai T, Ueno M, Kinoshita S, Koizumi N.
    • Journal Title

      Invest Ophthalmol Vis Sci.

      Volume: 1 Issue: 1 Pages: 318-29

    • DOI

      10.1167/iovs.13-12225

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Cultivation of Corneal Endothelial Cells on a Pericellular Matrix Prepared from Human Decidua-Derived Mesenchymal Cells.2014

    • Author(s)
      Numata R, Okumura N, Nakahara M, Ueno M, Kinoshita S, Kanematsu D, Kanemura Y, Sasai Y, Koizumi N
    • Journal Title

      Plos One

      Volume: 2 Issue: 2 Pages: e88169-e88169

    • DOI

      10.1371/journal.pone.0088169

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] The ROCK Inhibitor Eye Drop Accelerates Corneal Endothelium Wound Healing.2013

    • Author(s)
      Okumura N, Koizumi N, Kay EP, Ueno M, Sakamoto Y, Nakamura S, Hamuro J, Kinoshita S
    • Journal Title

      Invest Ophthalmol Vis Sci

      Volume: 54(4) Issue: 4 Pages: 2493-2502

    • DOI

      10.1167/iovs.12-11320

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Rho-associated kinase (ROCK) inhibitor eye drop treatment as a possible medical treatment for Fuchs corneal dystrophy.2013

    • Author(s)
      Koizumi N, Okumura N, Ueno M, Nakagawa H, Hamuro J, Kinoshita S
    • Journal Title

      Cornea

      Volume: 32(8) Issue: 8 Pages: 1167-70

    • DOI

      10.1097/ico.0b013e318285475d

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Corneal Endothelial Cell Fate is Maintained by LGR5 via the Regulation of Hedgehog and Wnt Pathway.2013

    • Author(s)
      Hirata-Tominaga K, Nakamura T, Okumura N, Kay EP, Barrandon Y, Koizumi N, Kinoshita S
    • Journal Title

      Stem Cells

      Volume: 7 Issue: 7 Pages: 1396-1407

    • DOI

      10.1002/stem.1390

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Corneal endothelial expansion promoted by human bone marrow mesenchymal stem cell-derived conditioned medium.2013

    • Author(s)
      Nakahara M, Okumura N, Kay EP, Hagiya M, Imagawa K, Hosoda Y, Kinoshita S, Koizumi N.
    • Journal Title

      PLOS ONE

      Volume: 7 Issue: 7 Pages: e69009-e69009

    • DOI

      10.1371/journal.pone.0069009

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Author Response: Human Corneal Endothelium Regeneration: Effect of ROCK Inhibitor.2013

    • Author(s)
      Koizumi N, Okumura N, Kinoshita S
    • Journal Title

      Invest Ophthalmol Vis Sci

      Volume: 19;54(8) Issue: 8 Pages: 5594-5

    • DOI

      10.1167/iovs.13-12813

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Ferret animal model of corneal endothelial dysfunction for evaluation of drug effect on corneal endothelial wound healing.2013

    • Author(s)
      Sakamoto Y, Okumura N, Koizumi N, Numata R, Kitano J, Yamamoto M, Komada T, Hoshi N
    • Journal Title

      Anim. Eye Res

      Volume: 32 Pages: 5-21

    • NAID

      130005061465

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Cultivated corneal endothelial cell injection for the treatment of bullous keratopathy.2014

    • Author(s)
      Okumura N
    • Organizer
      Seminar in Kyungpook National University Hospital
    • Place of Presentation
      Kyungpook National University Hospital
    • Year and Date
      2014-09-27
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Regenerative medicine for the treatment of corneal endothelial dysfunction.2014

    • Author(s)
      Okumura N
    • Organizer
      TERMIS-AP 2014
    • Place of Presentation
      Daegu, Korea
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Development of cell therapy for treating corneal endothelial dysfunction.2014

    • Author(s)
      Okumura N
    • Organizer
      Seminar in the Catholic University of Korea
    • Place of Presentation
      Catholic University of Korea
    • Year and Date
      2014-09-23
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Involvement of transforming growth factor beta in extracellular matrix deposition and endoplasmic reticulum stress in Fuchs' corneal dystrophy.2014

    • Author(s)
      Okumura N, Minamiyama R, Kay EP, Ho L, Kawasaki S, Young R, Quantock A, Schlotzer-Schrehardt U, Kruse F, Kinoshita S, Koizumi N
    • Organizer
      The International Society for Eye Research XXI Biennial Meeting
    • Place of Presentation
      San Francisco, California, USA
    • Year and Date
      2014-07-20 – 2014-07-23
    • Related Report
      2014 Annual Research Report
  • [Presentation] Modulating Cell Adhesion Property Enables Cell-based Therapy for Corneal Endothelial Dysfunction.2014

    • Author(s)
      Okumura N
    • Organizer
      The Association for Research in Vision and Ophthalmology 2014
    • Place of Presentation
      Florida, USA
    • Year and Date
      2014-05-05 – 2014-05-08
    • Related Report
      2014 Annual Research Report
  • [Presentation] Cell Line of Fuchs' Corneal Dystrophy Produces an Abnormal Extracellular Matrix.(ポスター)

    • Author(s)
      Leona Ho, Naoki Okumura, EunDuck P. Kay, Kenta Yamasaki, Satoshi Kawasaki, Theofilos Tourtas, Ursula Schlotzer-Schrehardt, Friedrich E. Kruse, Shigeru Kinoshita, Noriko Koizumi
    • Organizer
      The Association for Research in Vision and Ophthalmology 2013
    • Place of Presentation
      Seattle, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] Rho-kinase inhibitor enhances corneal endothelial cell proliferation via p27 degradation.(ポスター)

    • Author(s)
      Ryohei Numata, Naoki Okumura, EunDuck P. Kay, Makiko Nakahara, Shinichiro Nakano, Morio Ueno, Shigeru Kinoshita, Noriko Koizumi
    • Organizer
      The Association for Research in Vision and Ophthalmology 2013
    • Place of Presentation
      Seattle, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] Proliferation Propensity of Cultured Human Corneal Endothelial Cells and Their Plasticity Dictated by Culture Microenvironments.(ポスター)

    • Author(s)
      Munetoyo Toda, Kana Nakata, kazuko asada, Michio Hagiya, Morio Ueno, Naoki Okumura, Noriko Koizumi, Junji Hamuro, Shigeru Kinoshita
    • Organizer
      The Association for Research in Vision and Ophthalmology 2013
    • Place of Presentation
      Seattle, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] Cell-injection Therapy Using Rho Kinase Inhibitor in a Corneal Endothelial Dysfunction Rabbit Model.(ポスター)

    • Author(s)
      Junji Kitano, Naoki Okumura, EunDuck P. Kay, Morio Ueno, Junji Hamuro, Shigeru Kinoshita, Noriko Koizumi
    • Organizer
      The Association for Research in Vision and Ophthalmology 2013
    • Place of Presentation
      Seattle, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] Rho kinase inhibitor promotes cell adhesion of corneal endothelial cells through inhibiting phosphorylation of MLC.(ポスター)

    • Author(s)
      Yuki Tsujimoto, Naoki Okumura, EunDuck P. Kay, Ryohei Numata, Shigeru Kinoshita, Noriko Koizumi
    • Organizer
      The Association for Research in Vision and Ophthalmology 2013
    • Place of Presentation
      Seattle, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] Efficacy and Safety Evaluation of Cell-Injection Therapy using Cultivated Human Corneal Endothelial Cells.(口頭)

    • Author(s)
      Noriko Koizumi, Naoki Okumura, Takashi Shiina, Shingo Suzuki, Shinichiro Nakamura, Yuji Sakamoto, Kenta Yamasaki, Morio Ueno, Junji Hamuro, Shigeru Kinoshita
    • Organizer
      The Association for Research in Vision and Ophthalmology 2013
    • Place of Presentation
      Seattle, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] Development of a Human Cultivated Nasal Mucosal Epithelial Cell Sheet for the Treatment of Severe Ocular Surface Diseases.(ポスター)

    • Author(s)
      Masakazu Kobayashi, Takahiro Nakamura, Makoto Yasuda, Yuiko Hata, Shoki Okura, Naoki Okumura, Noriko Koizumi, Hisao Yasu, Shigeru Kinoshita
    • Organizer
      The Association for Research in Vision and Ophthalmology 2013
    • Place of Presentation
      Seattle, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] Integral Analysis of Gene Signatures and MicroRNA Expression of Cultured Human Corneal Endothelial Cells in Relation to Their Functions, Cell Senescence, Epithelial-Mesenchymal Transition, and Fibrosis.(口頭)

    • Author(s)
      Kazuko Asada, Munetoyo Toda, Michio Hagiya, Kana Nakata, Morio Ueno, Naoki Okumura, Noriko Koizumi, Junji Hamuro, Shigeru Kinoshita
    • Organizer
      The Association for Research in Vision and Ophthalmology 2013
    • Place of Presentation
      Seattle, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] The Effect of EMT-Related Genes on the Regulation of Excessive Production of Extracellular Matrix in a Cellular Model of Fuchs’ Corneal Dystrophy.

    • Author(s)
      Naoki Okumura, Leona Ho, EunDuck P. Kay, Satoshi Kawasaki, Theofilos Tourtas, Ursula Schlotzer-Schrehardt, Friedrich E. Kruse, Shigeru Kinoshita, Noriko Koizumi
    • Organizer
      Gordon Research Conference.
    • Place of Presentation
      California, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] Cell-Based Approach for the Treatment of Corneal Endothelial Dysfunction.(口頭)

    • Author(s)
      Naoki Okumura
    • Organizer
      Gordon Research Conference
    • Place of Presentation
      California, USA
    • Related Report
      2013 Research-status Report
  • [Presentation] The establishment of human corneal endothelial cell culture for clinical application(シンポジウム)

    • Author(s)
      Naoki Okumura
    • Organizer
      第117回日本眼科学会総会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] Rhoキナーゼ阻害剤の角膜内皮細胞に対するアポトーシス抑制効果の検討

    • Author(s)
      奥村直毅、小田嶋愛、EunDuck Kay、陳文、上野盛夫、羽室淳爾、木下茂、小泉範子
    • Organizer
      第117回日本眼科学会総会
    • Place of Presentation
      東京
    • Related Report
      2013 Research-status Report
  • [Presentation] 再生医療研究の最前線!トランスレーショナル・リサーチの実践(口頭)

    • Author(s)
      奥村直毅
    • Organizer
      第67回 日本臨床眼科学会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] Fuchs角膜内皮ジストロフィにおけるECM産生に対するTGF-βシグナルの影響(ポスター)

    • Author(s)
      奥村直毅、Ho Leona、Kay EunDuck、川崎諭、Tourtas Theofilos、Schlotzer Ursula、Kruse Friendrich、木下茂、小泉範子
    • Organizer
      角膜カンファランス2014第38回日本角膜学会総会・第30回日本角膜移植学会
    • Place of Presentation
      沖縄
    • Related Report
      2013 Research-status Report
  • [Presentation] 角膜内皮細胞培養におけるラミニン511および521の有用性(口頭)

    • Author(s)
      奥村直毅、沼田諒平、角谷和哉、Ursula Schlotzer、Friendrich Kruse、木下茂、小泉範子
    • Organizer
      第13回日本再生医療学会総会
    • Place of Presentation
      京都
    • Related Report
      2013 Research-status Report
  • [Remarks] 同志社大学ティッシュエンジニアリング研究室ホームページ

    • URL

      http://tissue-engineering-doshisha.jp/index.html

    • Related Report
      2014 Annual Research Report
  • [Remarks] ReaD & Researchmap

    • URL

      https://researchmap.jp/okumura.n/

    • Related Report
      2014 Annual Research Report

URL: 

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

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