Neuroprotection and regeneration by retinal glia

• Project/Area Number: 23890254
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Ophthalmology
• Research Institution: 公益財団法人東京都医学総合研究所 (2012); Tokyo Metropolitan Organization for Medical Research (2011)
• Principal Investigator: HARADA Chikako 公益財団法人東京都医学総合研究所, 運動・感覚システム研究分野, 研究員 (20435720)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: グリア / 神経保護 / 神経再生 / 神経栄養因子 / 視細胞 / 網膜神経節細胞 / 網膜 / Muller細胞 / 再生

Research Abstract

In this study, we prepared two conditional knockout mice, in which neurotrophic factor receptor (TrkB) is absent from retinal Muller glia or other neural cell types. By analyzing these mice, we found that neurotrophic factor signaling in glia is necessary for neuroprotection of surrounding retinal neurons and regeneration of glial cells into neural cells.

Research Products

• [Journal Article] Inhibition of ASK1-p38 pathway prevents neural cell death following optic nerve injury. (2013)
  • Author(s): Katome, T., Namekata, K., Guo, X., Semba, K., Kittaka, D., Kawamura, K., Kimura, A., Harada, C., Ichijo, H., Mitamura, Y. and Harada, T.
  • Journal Title: Cell Death Differ. Volume: 20 Issue: 2 Pages: 270-280
  • DOI: 10.1038/cdd.2012.122
  • Peer Reviewed
• [Journal Article] 網膜変性疾患とMAPキナーゼ (2013)
  • Author(s): 原田知加子、原田高幸
  • Journal Title: Clinical Neuroscience Volume: 31(6) Pages: 705-706
• [Journal Article] ASK1-p38 経路の阻害は視神経外傷後の神経細胞死を抑制する (2013)
  • Author(s): 香留 崇、行方和彦、郭 暁麗、仙波賢太郎、橘高大二、川村和人、木村敦子、原田知加子、一條秀憲、三田村佳典、原田高幸
  • Journal Title: 日眼会誌 Volume: 117(2) Pages: 161-161
• [Journal Article] ASK1-p38 経路の阻害は視神経外傷後の神経細胞死を抑制する. (2013)
  • Author(s): 香留 崇、他１０名
  • Journal Title: 日本眼科学会雑誌 Volume: 117 Pages: 161-161
• [Journal Article] 「神経系のMAPキナーゼ」網膜変性疾患とMAPキナーゼ. (2013)
  • Author(s): 原田知加子、原田高幸
  • Journal Title: Clinical Neuroscience Volume: 31
• [Journal Article] Expression of promyelocytic leukemia protein and vascular endothelial growth factor in aqueous humor and vitreous fluid in patients with proliferative diabetic retinopathy. (2012)
  • Author(s): Katome T, et al.
  • Journal Title: Diabetes Res Clin Pract Volume: 98 Issue: 2 Pages: 9-11
  • DOI: 10.1016/j.diabres.2012.09.020
  • Peer Reviewed
• [Journal Article] Dock3 regulates BDNF-TrkB signaling for neurite outgrowth by forming a ternary complex with Elmo and RhoG. (2012)
  • Author(s): Namekata K、他6名
  • Journal Title: Genes to Cells. Volume: 17 Issue: 8 Pages: 688-697
  • DOI: 10.1111/j.1365-2443.2012.01616.x
  • Peer Reviewed
• [Journal Article] Dock3 stimulates axonal outgrowth via GSK-3β-mediated microtubule assembly (2012)
  • Author(s): Namekata K., Harada C., Guo X., Kimura H., Kittaka D., Watanabe H., Harada T.
  • Journal Title: Journal of Neuroscience Volume: 32 Issue: 1 Pages: 264-274
  • DOI: 10.1523/jneurosci.4884-11.2012
  • Peer Reviewed
• [Journal Article] Dock3はグリコーゲン合成酵素キナーゼ-3β (GSK-3β)による微小管重合を介して軸索伸長を促進する (2012)
  • Author(s): 行方和彦、原田知加子、郭 暁麗、木村敦子、橘高大二、渡邉快記、原田高幸
  • Journal Title: 日眼会誌 Volume: 116(5) Pages: 527-527
• [Journal Article] Dock3はグリコーゲン合成酵素キナーゼ-3β (GSK-3β)による微小管重合を介して軸索伸長を促進する. (2012)
  • Author(s): 行方和彦、他７名
  • Journal Title: 日本眼科学会雑誌 Volume: 116 Pages: 527-527
• [Journal Article] bck3 stimulates axonal outgrowth via GSK-3β-mediated microtubule assembly (2012)
  • Author(s): Namekata K.
  • Journal Title: Journal of Neuroscience Volume: 32 Pages: 264-274
  • Peer Reviewed
• [Journal Article] Glia- and neuron-specific functions of TrkB signaling during retinal degeneration and regeneration (2011)
  • Author(s): Harada, C.
  • Journal Title: Nature Communications Volume: 2 Issue: 1 Pages: 1-9
  • DOI: 10.1038/ncomms1190
  • Peer Reviewed
• [Journal Article] Spermidine alleviates severity of murine experimental autoimmune encephalomyelitis (2011)
  • Author(s): Guo, X., Harada, C., Namekata, K., Kimura, A., Mitamura, Y., Yoshida, H., Matsumoto, Y., and Harada, T
  • Journal Title: Investigative Ophthalmology & Visual Science Volume: 52(5) Issue: 5 Pages: 2696-2703
  • DOI: 10.1167/iovs.10-6015
  • Peer Reviewed
• [Journal Article] Spermidine投与による実験的自己免疫性脳脊髄炎の軽症化 (2011)
  • Author(s): 郭 暁麗、原田知加子、行方和彦、木村敦子、三田村佳典、吉田 寛、松本 陽、原田高幸
  • Journal Title: 日眼会誌 Volume: 115(8) Pages: 729-729
• [Journal Article] 網膜の変性と再生過程におけるグリアおよび神経特異的なTrkBシグナルの機能解析 (2011)
  • Author(s): 原田知加子、郭 暁麗、行方和彦、木村敦子、中村和昭、田中光一、Luis F. Parada、原田高幸
  • Journal Title: 日眼会誌 Volume: 115(7) Pages: 637-637
• [Journal Article] TLR-ASK1-p38経路による神経炎症と脱髄症状の制御 (2011)
  • Author(s): 郭 暁麗、原田知加子、行方和彦、松沢 厚、Monsterrat Camps、Hong Ji、Dominique Swinnen、Catherine Jorand-Lebrun、Mathilde Muzerelle、Pierre-Alain Vitte、Thomas Ruckle、木村敦子、神山邦子、松本 陽、一條秀憲、原田高幸
  • Journal Title: 日眼会誌 Volume: 115(5) Pages: 485-485
• [Journal Article] Dock3 attenuates neural cell death due to NMDA neurotoxicity and oxidative stress in a mouse model of normal tension glaucoma
  • Author(s): Namekata, K., Kimura, A., Kawamura, K., Guo, X., Harada, C., Tanaka, K. and Harada, T
  • Journal Title: Cell Death and Differentiation Volume: (in press)
  • Peer Reviewed
• [Presentation] The role of Dock3 in axon regeneration following optic nerve injury (2012)
  • Author(s): Kazuhiko Namekata, Chikako Harada, Xiaoli Guo, Atsuko Kimura, Takayuki Harada
  • Organizer: XX International Congress of Eye Research (ISER 2012)
  • Place of Presentation: Berlin, Germany
  • Year and Date: 2012-07-24
• [Presentation] Session "Macrophages and microglial regulation of ocular inflammation" ASK1 inhibition ameliorates optic neuritis by modulating glial innate immunity (2012)
  • Author(s): Xiaoli Guo, Chikako Harada, Kazuhiko Namekata, Atsuko Kimura, Takayuki Harada
  • Organizer: XX International Congress of Eye Research (ISER2012)
  • Place of Presentation: Berlin, Germany
  • Year and Date: 2012-07-23
• [Presentation] Dock3によるマウス視神経軸索再生効果の検討 (2012)
  • Author(s): 原田高幸、行方和彦、原田知加子
  • Organizer: 第116回 日本眼科学会総会
  • Place of Presentation: 東京国際フォーラム
  • Year and Date: 2012-04-06
• [Presentation] The role of Dock3 in axon regeneration following optic nerve injury. (2012)
  • Author(s): Kazuhiko Namekata、他４名
  • Organizer: XX International Congress of Eye Research (ISER2012)
  • Place of Presentation: Berlin, Germany
• [Presentation] ASK1 inhibition ameliorates optic neuritis by modulating glial innate immunity. (2012)
  • Author(s): Xiaoli Guo、他５名
  • Organizer: XX International Congress of Eye Research (ISER2012)
  • Place of Presentation: Berlin, Germany.
• [Presentation] Dock3によるマウス視神経軸索再生効果の検討. (2012)
  • Author(s): 原田高幸、行方和彦、原田知加子
  • Organizer: 第116回日本眼科学会総会
  • Place of Presentation: 東京国際フォーラム
• [Presentation] Glia- and neuron-specific functions of TrkB signaling during retinal degeneration and regeneration (2011)
  • Author(s): Takayuki Harada, Xiaoli Guo, Kazuhiko Namekata, Luis F. Parada, Chikako Harada
  • Organizer: 8th World Congress of Neuroscience, International Brain Research Organization (IBRO)
  • Place of Presentation: Florence, Italy
  • Year and Date: 2011-07-18
• [Presentation] ia- and neuron-specific functions of TrkB signaling during retinal degeneration and regenerati (2011)
  • Author(s): Harada T.
  • Organizer: the 8th IBRO World Congress of Neuroscience
  • Place of Presentation: フィレンツェ(イタリア)
  • Year and Date: 2011-07-18
• [Presentation] ASK1 deficiency attenuates neural cell death in a mouse model of normal tension glaucoma (2011)
  • Author(s): Takayuki Harada, Kazuhiko Namekata, Xiaoli Guo, Kohichi Tanaka, Hidenori Ichijo, Chikako Harada
  • Organizer: The 26th Asia Pacific Academy of Ophthalmology (APAO) Congress
  • Place of Presentation: Sydney, Australia
  • Year and Date: 2011-03-22
• [Presentation] Optic nerve regeneration is enhanced in Dock3 overexpressing transgenic mice (2011)
  • Author(s): Kazuhiko Namekata, Chikako Harada, Xiaoli Guo, Takayuki Harada
  • Organizer: The 26th Asia Pacific Academy of Ophthalmology (APAO) Congress
  • Place of Presentation: Sydney, Australia
  • Year and Date: 2011-03-22
• [Presentation] ASK1 inhibition ameliorates optic neuritis by modulating glial innate immunity (2011)
  • Author(s): Xiaoli Guo, Chikako Harada, Kazuaki Nakamura, Atsuko Kimura, Hidenori Ichijo, Takayuki Harada
  • Organizer: The 26th Asia Pacific Academy of Ophthalmology (APAO) Congress
  • Place of Presentation: Sydney, Australia
  • Year and Date: 2011-03-22
• [Remarks] 視覚病態プロジェクトの研究紹介
  • URL: http://www.igakuken.or.jp/retina/
• [Remarks]
  • URL: http://www.igakuken.or.jp/retina/