Study on mechanism controlling injury tissue remodeling related to retinal regeneration

• Project/Area Number: 26462693
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Kumamoto University
• Principal Investigator: Fukushima Mikiko 熊本大学, 大学院生命科学研究部(医), 准教授 (10284770)
• Co-Investigator(Kenkyū-buntansha): 井上 俊洋 熊本大学, 医学部附属病院, 講師 (00317025) ; 高橋 枝里 熊本大学, 大学院生命科学研究部(医), 助教 (60622602) ; 伊藤 康裕 熊本大学, 医学部附属病院, 助教 (70380996)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 眼科学 / 組織再生 / 再生医学 / 細胞・組織

Outline of Final Research Achievements

The present study investigated cellular and molecular mechanisms concerned with tissue damage and fibrosis. 1. Characteristics and functions of microglia induced in injured tissue in the optic nerve crush model, and related molecular signals were clarified. 2. Cytokines and growth factor in aqueous humor samples were increased in patients with uveitic and neovascular glaucoma. In retinal pigment cell culture analysis, vitreous samples in patients with retinal detachment and epimacular membrane induced epithelial-transformation. 3. Epigenetic modification was revealed as one of the molecular mechanisms that controls tissue fibrosis.

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 Issue: 4 Pages: 2421-2429
  • DOI: 10.1167/iovs.16-21403
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Factors Influencing Aqueous Proinflammatory Cytokines and Growth Factors in Uveitic Glaucoma. (2016)
  • Author(s): Ohira S, Inoue T, Iwao K, Takahashi E, Tanihara H.
  • Journal Title: PLoS One Volume: 11 Issue: 1 Pages: e0147080-e0147080
  • DOI: 10.1371/journal.pone.0147080
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Visualization of Intravital Immune Cell Dynamics After Conjunctival Surgery Using Multiphoton Microscopy. (2016)
  • Author(s): Kojima S, Inoue T, Kikuta J, Furuya M, Koga A, Fujimoto T, Ueta M, Kinoshita S, Ishii M, Tanihara H.
  • Journal Title: Investigative Ophthalmology & Visual Science Volume: 57 Issue: 3 Pages: 1207-1212
  • DOI: 10.1167/iovs.15-18507
  • 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 / Open Access
• [Journal Article] Potential neuroprotective effects of an LSD1 inhibitor in retinal ganglion cells via p38 MAPK-gamma activity (2016)
  • Author(s): T. Tsutsumi, K. Iwao, H. Hayashi, T. Kawaji, T. Inoue, S. Hino, M. Nakao, and H. Tanihara.
  • Journal Title: Invest. Ophthalmol. Vis. Sci. Volume: 57 Issue: 14 Pages: 6461-6473
  • DOI: 10.1167/iovs.16-19494
  • Peer Reviewed / Open Access
• [Journal Article] Effects of mechanical stress and vitreous samples in retinal pigment epithelial cells. (2016)
  • Author(s): Takahashi E, Fukushima A, Haga A, Inomata Y, Ito Y, Fukushima M, Tanihara H.
  • Journal Title: Biochem Biophys Res Commun. Volume: 470 Issue: 3 Pages: 569-74
  • DOI: 10.1016/j.bbrc.2016.01.104
  • Peer Reviewed / Open Access
• [Journal Article] Simultaneous increase in multiple proinflammatory cytokines in the aqueous humor in neovascular glaucoma with and without intravitreal bevacizumab injection (2015)
  • Author(s): Ohira S, Inoue T, Shobayashi K, Iwao K, Fukushima M, Tanihara H
  • Journal Title: Investigative Ophthalmology & Visual Science Volume: 56 Issue: 6 Pages: 3541-3548
  • DOI: 10.1167/iovs.14-15918
  • Peer Reviewed / Open Access
• [Journal Article] Merlin regulates the epithelial-to-mesenchymal transition of ARPE-19 cells via TAK1-p38MAPK-mediated activation. (2015)
  • Author(s): Takahashi E, Haga A, Tanihara H.
  • Journal Title: Invest Ophthalmol Vis Sci. Volume: 56 Issue: 4 Pages: 2449-2458
  • DOI: 10.1167/iovs.14-16300
  • Peer Reviewed
• [Journal Article] Simultaneous Increase in Multiple Proinflammatory Cytokines in the Aqueous Humor in Neovascular Glaucoma with and without Intravitreal Bevacizumab Injection. (2015)
  • Author(s): Ohira S, Inoue T, Shobayashi K, Iwao, K, Fukushima M, Tanihara H.
  • Journal Title: Invest Ophthalmol Vis Sci. Volume: -
  • Peer Reviewed
• [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] p38 MAP Kinase Inhibitor Suppresses Transforming Growth Factor-β2-Induced Type 1 Collagen Production in Trabecular Meshwork Cells. (2014)
  • 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 Issue: 3 Pages: 1-13
  • DOI: 10.1371/journal.pone.0120774
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Monocyte chemotactic protein-1 level in the aqueous humor as a prognostic factor for the outcome of trabeculectomy (2013)
  • Author(s): Inoue T, Kawaji T, Tanihara H
  • Journal Title: Clinical and Experimental Ophthalmology Volume: (in press) Issue: 4 Pages: 334-341
  • DOI: 10.1111/ceo.12204
  • Peer Reviewed
• [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: ARVO Annual Meeting 2014
  • Place of Presentation: オーランド， 米国
  • Year and Date: 2014-05-04 – 2014-05-08
• [Presentation] Effects of p38 inhibitor on TGF-β signal in trabecular meshwork cells (2014)
  • Author(s): Inoue-Mochita M, Inoue T, Fujimoto T, Awai-Kasaoka N, Tanihara H.
  • Organizer: ARVO Annual Meeting 2014
  • Place of Presentation: オーランド，米国
  • Year and Date: 2014-05-04 – 2014-05-08