The regulation of bioactive molecule dynamics and development of real-time imaging technics for glaucoma therapy.

2016 Fiscal Year Annual Research Report

• Project/Area Number: 26293375
• Research Institution: Kumamoto University
• Principal Investigator: 谷原 秀信 熊本大学, その他の研究科, 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) ; 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, その他の研究科, 助教 (60622602)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 緑内障 / 生理活性 / シグナル伝達

Outline of Annual Research Achievements

眼内環境における生理活性物質の動的均衡とリアルタイムイメージング（real-time imaging; RTI）技術の開発により、緑内障病態を踏まえた治療研究を目指している。本年度は最終年度であることから臨床応用にターゲットを置き(1)房水流出路の前眼部OCT装置を用いたRTI技術による手術治療の解析、(2)緑内障手術に関連した結膜創傷治癒における炎症細胞挙動のRTI評価を中心に行った。内眼手術既往のある緑内障濾過手術のハイリスク症例に対する前向き研究を実施し、前眼部OCTを用いたRTIによる濾過胞形状の解析により、術後早期の強膜フラップ縁の開口部の幅が、術後の眼圧コントロールに関係することが推察された。結膜創傷治癒に関する基礎研究として、動物モデルにおいて濾過胞の維持効果が報告されているROCK阻害剤が結膜線維芽細胞のTGF-β刺激による筋線維芽細胞への形質転換を抑制することを明らかにした。さらにエピジェネティクス薬のヒストン脱アセチル化酵素阻害剤であるボリノスタットは、TGF-βシグナルのSmad2、Smad3、p38、Aktのリン酸化を抑制し筋線維芽細胞への形質転換を抑制することを明らかにした。さらに結膜線維芽細胞培養上清中の血管新生関連サイトカインであるPDGF-AA、VEGFがボリノスタットにより減少し、ボリノスタットで処置した結膜線維芽細胞培養上清ではHUVEC細胞の血管形成が抑制されることを示した。これらの結果は、緑内障手術後の濾過胞維持という新たな緑内障治療法の可能性を示すものと考えられる。

Research Progress Status

28年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

28年度が最終年度であるため、記入しない。

Causes of Carryover

28年度が最終年度であるため、記入しない。

Expenditure Plan for Carryover Budget

28年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] Molecular mechanisms underlying the filtration bleb-maintaining effects of suberoylanilide hydroxamic acid (SAHA). (2017)
  • Author(s): Futakuchi A, Inoue T, Fujimoto T, Kuroda U, Inoue-Mochita M, Takahashi E, Ohira S, Tanihara H.
  • Journal Title: Investigative Ophthalmology & Visual Sciences Volume: 58 Pages: 2421-2429
  • DOI: 10.1167/iovs.16-21403.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Prospective observation of filtration blebs in high-risk eyes with limbal-based conjunctival flap. (2016)
  • Author(s): Matsumoto M, Inoue T, Kojima S, Nakashima KI, Fukushima A, Tanihara H.
  • Journal Title: Canadian Journal of Ophthalmology Volume: 51 Pages: 431-437
  • DOI: 10.1016/j.jcjo.2016.05.019.
  • Peer Reviewed
• [Journal Article] Potential Neuroprotective Effects of an LSD1 Inhibitor in Retinal Ganglion Cells via p38 MAPK Activity. (2016)
  • Author(s): Tsutsumi T, Iwao K, Hayashi H, Kirihara T, Kawaji T, Inoue T, Hino S, Nakao M, Tanihara H.
  • Journal Title: Investigative Ophthalmology & Visual Sciences Volume: 57 Pages: 6461-6473
  • DOI: 10.1167/iovs.16-19494.
  • Peer Reviewed
• [Journal Article] Change in visual acuity and associated risk factors after trabeculectomy with adjunctive mitomycin C. (2016)
  • Author(s): Kashiwagi K, Kogure S, Mabuchi F, Chiba T, Yamamoto T, Kuwayama Y, Araie M; Collaborative Bleb-Related Infection Incidence and Treatment Study Group.
  • Journal Title: Acta Ophthalmologica Volume: 94 Pages: e561-e570
  • DOI: 10.1111/aos.13058.
  • Peer Reviewed
• [Journal Article] Comparing Trabeculectomy Outcomes between First and Second Operated Eyes: A Multicenter Study. (2016)
  • Author(s): Iwasaki K, Takamura Y, Nishida T, Sawada A, Iwao K, Shinmura A, Kunimatsu-Sanuki S, Yamamoto T, Tanihara H, Sugiyama K, Nakazawa T, Inatani M.
  • Journal Title: PLoS One Volume: 11 Pages: e0162569
  • DOI: 10.1371/journal.pone.0162569
  • Peer Reviewed / Open Access
• [Journal Article] Vascular Endothelial Growth Factor-A Increases the Aqueous Humor Outflow Facility. (2016)
  • Author(s): Fujimoto T, Inoue T, Maki K, Inoue-Mochita M, Tanihara H.
  • Journal Title: PLoS One Volume: 11 Pages: e0161332
  • DOI: 10.1371/journal.pone.0161332.
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] The effects of ripasudil (K-115), a Rho kinase inhibitor, on activation of human conjunctival fibroblasts. (2016)
  • Author(s): Futakuchi A, Inoue T, Fujimoto T, Inoue-Mochita M, Kawai M, Tanihara H.
  • Journal Title: Experimental Eye Research Volume: 149 Pages: 107-115
  • DOI: 10.1016/j.exer.2016.07.001.
  • Peer Reviewed
• [Journal Article] Differentiated Expression Patterns and Phagocytic Activities of Type 1 and 2 Microglia. (2016)
  • Author(s): Haga A, Takahashi E, Inomata Y, Kawahara K, Tanihara H.
  • Journal Title: Investigative Ophthalmology & Visual Sciences Volume: 57 Pages: 2814-2823
  • DOI: 10.1167/iovs.15-18509.
  • Peer Reviewed
• [Journal Article] Angle closure caused by a plateau-like iris associated with an enlarged Soemmering's ring: a case report. (2016)
  • Author(s): Kitamura F, Inoue T, Kuroda U, Tanihara H.
  • Journal Title: BMC Ophthalmology Volume: 16 Pages: 49
  • DOI: 10.1186/s12886-016-0226-0
  • Peer Reviewed
• [Presentation] Effects of interleukin (IL)-6 signaling activity on fibrogenic activity of human trabecular meshwork cells. (2016)
  • Author(s): Inoue T, Inoue-Mochita, M, Fujimoto T, Tanihara H.
  • Organizer: 12th European Glaucoma Society (EGS) Congress
  • Place of Presentation: Prague, Czech Republic
  • Year and Date: 2016-06-19 – 2016-06-22
  • Int'l Joint Research
• [Presentation] Effects of ripasudil (K-115), a Rho kinase inhibitor, on the activation of human conjunctival fibroblasts. (2016)
  • Author(s): Futakuchi A, Inoue T, Fujimoto T, Inoue-Mochita M, Tanihara H.
  • Organizer: The Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO)
  • Place of Presentation: Seatle, Washington, USA
  • Year and Date: 2016-05-01 – 2016-05-05
  • Int'l Joint Research
• [Presentation] Specific clinical features of intraocular pressure-lowering effect in ripasudil (K-115): insights from 52-week phase 3 study. (2016)
  • Author(s): Tanihara H, Inoue T, Yamamoto T, Kuwayama Y, Abe H, Fukushima A, Suganami H, Araie M.
  • Organizer: The Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO)
  • Place of Presentation: Seatle, Washington, USA
  • Year and Date: 2016-05-01 – 2016-05-05
  • Int'l Joint Research
• [Presentation] Effects of interleukin (IL)-6 signaling activity on fibrogenic activity of human trabecular meshwork cells. (2016)
  • Author(s): Inoue T, Inoue-Mochita, M, Fujimoto T, Tanihara H.
  • Organizer: The Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO)
  • Place of Presentation: Seatle, Washington, USA
  • Year and Date: 2016-05-01 – 2016-05-05
  • Int'l Joint Research
• [Presentation] Vascular endothelial growth factor-A increases aqueous humor outflow facility. (2016)
  • Author(s): Fujimoto T, Inoue T, Kei Maki, Inoue-Mochita M, Kojima S, Tanihara H.
  • Organizer: The Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO)
  • Place of Presentation: Seatle, Washington, USA
  • Year and Date: 2016-05-01 – 2016-05-05
  • Int'l Joint Research
• [Presentation] Four-dimensional imaging revealed influences of monocyte chemoattractant protein-1 on immune cell dynamics in the subconjunctival tissue. (2016)
  • Author(s): Kojima S, Inoue T, Fujioto T, Tanihara H.
  • Organizer: The Annual Meeting of the Association for Research in Vision and Ophthalmology (ARVO)
  • Place of Presentation: Seatle, Washington, USA
  • Year and Date: 2016-05-01 – 2016-05-05
  • Int'l Joint Research