• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2014 Fiscal Year Annual Research Report

生理活性物質の動的均衡制御とリアルタイムイメージング技術開発による緑内障治療研究

Research Project

Project/Area Number 26293375
Research InstitutionKumamoto University

Principal Investigator

谷原 秀信  熊本大学, 生命科学研究部, 教授 (60217148)

Co-Investigator(Kenkyū-buntansha) 井上 俊洋  熊本大学, 医学部附属病院, 講師 (00317025)
川路 隆博  熊本大学, 医学部附属病院, 講師 (30423677)
岩尾 圭一郎  熊本大学, 医学部附属病院, 助教 (30549118)
高橋 枝里  熊本大学, 生命科学研究部, 助教 (60622602)
Project Period (FY) 2014-04-01 – 2017-03-31
Keywords生理活性 / 生体分子 / シグナル伝達
Outline of Annual Research Achievements

房水・硝子体液中の生理活性物質のプロテオミクス的解析を行い、眼内に局在する生理活性物質群の動的均衡と病的状態における均衡レベルのシフトが眼圧制御および網膜神経節細胞死に対して与える影響を解析している。
まず、緑内障病型毎に房水サンプルを回収し、生理活性物質組成を評価した。その結果、正常眼(白内障眼)、原発開放隅角緑内障と比較して、ぶどう膜炎続発緑内障眼は炎症性サイトカインであるIL-6, -8、TNFαに加え、MCP1やVEGF濃度が上昇し、さらに血管新生緑内障では、更にその傾向が顕著であることが確認された。
また、代表的な緑内障眼における生理活性物質であるTGFβ2が房水流出主経路に与える影響について解析した。培養ヒト線維柱帯細胞において、TGFβ2刺激による1型コラーゲン合成が、Smad2/3分子を介して生じており、p38キナーゼ選択的遮断薬を使用することで阻害することを証明した。
さらに臨床研究として、濾過手術の前向き調査を行い、前眼部光干渉断層計(OCT)によって濾過胞形状を解析した。その結果、濾過胞形状の定量的解析を行うとともに、強膜フラップの性状についても評価を行い、術後12か月時点での眼圧が、術後0.5か月時点での濾過開口幅に規定されており、また、房水中MCP-1濃度がこの濾過開口幅に関連する可能性が示唆される結果を得た。

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

房水・硝子体液中の生理活性物質のプロテオミクス的解析を行い、眼内に局在する生理活性物質群の動的均衡と緑内障病態における均衡レベルのシフトを解析を進行させている。十分な症例数の緑内障病型毎の房水サンプルを採取し、房水内生理活性物質組成と手術治療成績・濾過胞形態との関連解析を進行できている。また、細胞骨格分布や細胞-細胞間結合装置の評価に関しても、in vitro定量評価系や前眼部灌流システムをを用いて、房水流出路へのTGFβをはじめとする生理活性物質の影響を予定通り解析できている。
以上のことから、おおむね順調に進展していると判断した。

Strategy for Future Research Activity

緑内障濾過手術における前眼部OCTイメージングによる濾過経路の観察と定量評価を進行させる。術前に採取した房水中生理活性物質濃度と画像解析パラメータとの関連性について検証を行う。また同時に、房水中生理活性物質濃度と術後眼圧成績の関連について、前向き観察試験を施行する。各種生理活性物質濃度を含めた危険因子を解析する。
緑内障手術動物モデルを使用して、リアルタイムイメージング技術を用いた創傷治癒応答の解析を予定する。
好中球がラベルされるLysosome M-EGFPマウスと単球/マクロファージがラベルされるCX3CR1-EGFPマウスを用いることで、結膜下免疫反応を2光子顕微鏡により4次元イメージング画像を取得し評価する。

  • Research Products

    (25 results)

All 2015 2014 Other

All Journal Article (15 results) (of which Peer Reviewed: 15 results,  Open Access: 5 results,  Acknowledgement Compliant: 8 results) Presentation (9 results) Remarks (1 results)

  • [Journal Article] Additive Intraocular Pressure-Lowering Effects of the Rho Kinase Inhibitor Ripasudil (K-115) Combined With Timolol or Latanoprost: A Report of 2 Randomized Clinical Trials.2015

    • Author(s)
      Tanihara H, Inoue T, Yamamoto T, Kuwayama Y, Abe H, Suganami H, Araie M; K-115 Clinical Study Group.
    • Journal Title

      JAMA Ophthalmology

      Volume: 133 Pages: 755-761

    • DOI

      10.1001/jamaophthalmol.2015.0525.

    • Peer Reviewed / Open Access
  • [Journal Article] Evaluation of filtering blebs exhibiting transconjunctival oozing using anterior segment optical coherence tomography.2015

    • Author(s)
      Nakashima K, Inoue T, Fukushima A, Hirakawa S, Kojima S, Tanihara H.
    • Journal Title

      Graefe's Archives of Clinical and Experimental Ophthalmology

      Volume: 253 Pages: 439-445

    • DOI

      10.1007/s00417-014-2872-3.

    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Efficacy and safety of SNJ-1656 in primary open-angle glaucoma or ocular hypertension.2015

    • Author(s)
      Inoue T, Tanihara H, Tokushige H, Araie M.
    • Journal Title

      Acta Ophthalmologica

      Volume: 印刷中 Pages: 印刷中

    • DOI

      10.1111/aos.12641.

    • Peer Reviewed
  • [Journal Article] p38 MAP Kinase Inhibitor Suppresses Transforming Growth Factor-β2-Induced Type 1 Collagen Production in Trabecular Meshwork Cells.2015

    • Author(s)
      Inoue-Mochita M, Inoue T, Fujimoto T, Kameda T, Awai-Kasaoka N, Ohtsu N, Kimoto K, Tanihara H.
    • Journal Title

      PLoS One

      Volume: 10 Pages: e0120774

    • DOI

      10.1371/journal.pone.0120774.

    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Phase 1 clinical trials of a selective Rho kinase inhibitor, K-115.2014

    • Author(s)
      Tanihara H, Inoue T, Yamamoto T, Kuwayama Y, Abe H, Araie M; K-115 Clinical Study Group.
    • Journal Title

      JAMA Ophthalmology

      Volume: 132 Pages: 1288-1295

    • DOI

      10.1001/jamaophthalmol.2013.323.

    • Peer Reviewed
  • [Journal Article] Monocyte chemotactic protein-1 level in the aqueous humour as a prognostic factor for the outcome of trabeculectomy.2014

    • Author(s)
      Inoue T, Kawaji T, Tanihara H.
    • Journal Title

      Clinical and Experimental Ophthalmology

      Volume: 42 Pages: 334-341

    • DOI

      10.1111/ceo.12204.

    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Trabeculectomy for open-angle glaucoma in phakic eyes vs in pseudophakic eyes after phacoemulsification: a prospective clinical cohort study.2014

    • Author(s)
      Takihara Y, Inatani M, Ogata-Iwao M, Kawai M, Inoue T, Iwao K, Tanihara H.
    • Journal Title

      JAMA Ophthalmology

      Volume: 132 Pages: 69-76

    • DOI

      10.1001/jamaophthalmol.2013.5605.

    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Epithelial mesenchymal transition-like phenomenon in trabecular meshwork cells.2014

    • Author(s)
      Takahashi E, Inoue T, Fujimoto T, Kojima S, Tanihara H.
    • Journal Title

      Experimental Eye Research

      Volume: 118 Pages: 72-79

    • DOI

      10.1016/j.exer.2013.11.014.

    • Peer Reviewed
  • [Journal Article] The 5-year incidence of bleb-related infection and its risk factors after filtering surgeries with adjunctive mitomycin C: collaborative bleb-related infection incidence and treatment study 2.2014

    • Author(s)
      Yamamoto T, Sawada A, Mayama C, Araie M, Ohkubo S, Sugiyama K, Kuwayama Y; Collaborative Bleb-Related Infection Incidence and Treatment Study Group.
    • Journal Title

      Ophthalmology.

      Volume: 121 Pages: 1001-1006

    • DOI

      10.1016/j.ophtha.2013.11.025.

    • Peer Reviewed
  • [Journal Article] Tear fluid signs associated with filtration blebs, as demonstrated by three-dimensional anterior segment optical coherence tomography.2014

    • Author(s)
      Kojima S, Inoue T, Kawaji T, Tanihara H.
    • Journal Title

      Clinical Ophthalmology

      Volume: 8 Pages: 767-772.

    • DOI

      10.2147/OPTH.S59778.

    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Long-term outcomes and complications of trabeculectomy for secondary glaucoma in patients with familial amyloidotic polyneuropathy.2014

    • Author(s)
      Kawaji T, Inoue T, Hara R, Eiki D, Ando Y, Tanihara H.
    • Journal Title

      PLoS One

      Volume: 9 Pages: e96324

    • DOI

      10.1371/journal.pone.0096324.

    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Fornix-based versus limbal-based conjunctival flaps in trabeculectomy with mitomycin C in high-risk patients.2014

    • Author(s)
      Kuroda U, Inoue T, Awai-Kasaoka N, Shobayashi K, Kojima S, Tanihara H.
    • Journal Title

      Clinical Ophthalmology

      Volume: 8 Pages: 949-954

    • DOI

      10.2147/OPTH.S61342.

    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Filtering blebs using 3-dimensional anterior-segment optical coherence tomography: a prospective investigation.2014

    • Author(s)
      Kojima S, Inoue T, Nakashima K, Fukushima A, Tanihara H.
    • Journal Title

      JAMA Ophthalmology

      Volume: 133 Pages: 148-156

    • DOI

      10.1001/jamaophthalmol.2014.4489.

    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Intra-ocular pressure-lowering effects of a Rho kinase inhibitor, ripasudil (K-115), over 24 hours in primary open-angle glaucoma and ocular hypertension: a randomized, open-label, crossover study.2014

    • Author(s)
      Tanihara H, Inoue T, Yamamoto T, Kuwayama Y, Abe H, Suganami H, Araie M; the K-115 Clinical Study Group.
    • Journal Title

      Acta Ophthalmologica

      Volume: 印刷中 Pages: 印刷中

    • DOI

      10.1111/aos.12599.

    • Peer Reviewed
  • [Journal Article] Long-term outcomes and prognostic factors for trabeculectomy with mitomycin C in eyes with uveitic glaucoma: a retrospective cohort study.2014

    • Author(s)
      Iwao K, Inatani M, Seto T, Takihara Y, Ogata-Iwao M, Okinami S, Tanihara H.
    • Journal Title

      Journal of Glaucoma

      Volume: 23 Pages: 88-94

    • DOI

      10.1097/IJG.0b013e3182685167.

    • Peer Reviewed
  • [Presentation] Prospective investigation of filtering bleb by three-dimensional anterior-segment optical coherence tomography.2014

    • Author(s)
      Inoue T, Kojima S, Fukushima A, Nakashima K, Tanihara H.
    • Organizer
      European Glaucoma Society 2014
    • Place of Presentation
      Nice, France
    • Year and Date
      2014-06-07 – 2014-06-11
  • [Presentation] Postoperative changes in the aqueous monocyte chemotactic protein-1 (MCP-1) level after trabeculectomy vs. Ex-PRESS shunt.2014

    • Author(s)
      Shobayashi K, Inoue T, Kawai M, Tanihara H.
    • Organizer
      European Glaucoma Society 2014
    • Place of Presentation
      Nice, France
    • Year and Date
      2014-06-07 – 2014-06-11
  • [Presentation] Immune cell dynamics around the subconjunctival tissue after injury by four dimensional in vivo imaging.2014

    • Author(s)
      Kojima S, Inoue T, Tanihara H.
    • Organizer
      European Glaucoma Society 2014
    • Place of Presentation
      Nice, France
    • Year and Date
      2014-06-07 – 2014-06-11
  • [Presentation] Live cell imaging of F-actin in dexamethasone treated trabecular meshwork cells.2014

    • Author(s)
      Fujimoto T, Inoue T, Inoue-Mochita M, Tanihara H.
    • Organizer
      European Glaucoma Society 2014
    • Place of Presentation
      Nice, France
    • Year and Date
      2014-06-07 – 2014-06-11
  • [Presentation] Prospective investigation of filtering bleb by three-dimensional anterior-segment optical coherence tomography.2014

    • Author(s)
      Inoue T, Kojima S, Fukushima A, Nakashima K, Tanihara H.
    • Organizer
      The Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO)
    • Place of Presentation
      Orlando, Florida, USA
    • Year and Date
      2014-05-04 – 2014-05-08
  • [Presentation] Effects of p38 inhibitor on TGF-β2 signal in trabecular meshwork cells.2014

    • Author(s)
      Inoue-Mochita M, Inoue T, Fujimoto T, Awai-Kasaoka N, Tanihara H.
    • Organizer
      The Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO)
    • Place of Presentation
      Orlando, Florida, USA
    • Year and Date
      2014-05-04 – 2014-05-08
  • [Presentation] Live cell imaging of F-actin in dexamethasone treated trabecular meshwork cells.2014

    • Author(s)
      Fujimoto T, Inoue T, Inoue-Mochita M, Tanihara H.
    • Organizer
      The Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO)
    • Place of Presentation
      Orlando, Florida, USA
    • Year and Date
      2014-05-04 – 2014-05-08
  • [Presentation] Investigation of Multiple Proinflammatory Cytokines in the Aqueous Humor in Eyes with Neovascular Glaucoma.2014

    • Author(s)
      Ohira S, Inoue T, Tanihara H.
    • Organizer
      The Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO)
    • Place of Presentation
      Orlando, Florida, USA
    • Year and Date
      2014-05-04 – 2014-05-08
  • [Presentation] K-115 Clinical Study Group. Phase 3 randomized clinical study of a Rho kinase inhibitor, K-115, in combination with timolol or latanoprost in primary open-angle glaucoma and ocular hypertension.2014

    • Author(s)
      Tanihara H, Yamamoto T, Kuwayama Y, Abe H, Inoue T, Araie M
    • Organizer
      World Ophthalmology Congress 2014
    • Place of Presentation
      Tokyo
    • Year and Date
      2014-04-02 – 2014-04-06
  • [Remarks] 熊本大学大学院生命科学研究部眼科学分野 研究内容

    • URL

      http://www2.kuh.kumamoto-u.ac.jp/ganka/kyousitu/naiyou.html

URL: 

Published: 2016-06-01  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi