Functional analyses of the role of oncomodulin in axon regeneration

• Project/Area Number: 26640048
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: HARADA Takayuki 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, 分野長 (90345306)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 軸索再生 / Oncomodulin / oncomodulin

Outline of Final Research Achievements

We tried to identify the receptor for oncomodulin and found several possible molecules. Overexpression of some of these molecules enhanced oncomodulin-mediated axon regeneration of retinal ganglion cells in vitro. We will continue to analyze other molecules and elucidate in detail the molecular pathways for oncomodulin.

Research Products

• [Journal Article] TrkB signaling in retinal glia stimulates neuroprotection after optic nerve injury. (2015)
  • Author(s): Harada, C., Azuchi, Y., Noro, T., Guo, X., Kimura, A., Namekata, K., Harada, T.
  • Journal Title: American Journal of Pathology Volume: 185 Issue: 12 Pages: 3238-3247
  • DOI: 10.1016/j.ajpath.2015.08.005
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Spermidine promotes retinal ganglion cell survival and optic nerve regeneration in adult mice following optic nerve injury. (2015)
  • Author(s): Noro, T., Namekata, K., Kimura, A., Guo, X., Azuchi, Y., Harada, C., Nakano, T., Tsuneoka, H. and Harada, T.
  • Journal Title: Cell Death and Disease Volume: 6 Issue: 4 Pages: e1720-e1720
  • DOI: 10.1038/cddis.2015.93
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Spermidine ameliorates neurodegeneration in a mouse model of normal tension glaucoma. (2015)
  • Author(s): Noro, T., Namekata, K., Azuchi, Y., Kimura, A., Guo, X., Harada, C., Nakano, T., Tsuneoka, H., Harada, T.
  • Journal Title: Investigative Ophthalmology & Visual Science Volume: 56 Issue: 8 Pages: 5012-5019
  • DOI: 10.1167/iovs.15-17142
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Brimonidine suppresses loss of retinal neurons and visual function in a murine model of optic neuritis (2015)
  • Author(s): Guo, X., Namekata, K., Kimura, A., Noro, T., Azuchi, Y., Semba, K., Harada, C., Yoshida, H., Mitamura, Y. and Harada, T.
  • Journal Title: Neuroscience Letters Volume: 592 Pages: 27-31
  • DOI: 10.1016/j.neulet.2015.02.059
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Expression of intraocular peroxisome proliferator-activated receptor gamma in patients with proliferative diabetic retinopathy. (2015)
  • Author(s): Katome T, Namekata K, Mitamura Y, Semba K, Egawa M, Naito T, Harada C, Harada T
  • Journal Title: J Diabetes Complications Volume: 29 Issue: 2 Pages: 275-281
  • DOI: 10.1016/j.jdiacomp.2014.10.010
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Arundic acid attenuates retinal ganglion cell death by increasing glutamate/aspartate transporter expression in a model of normal tension glaucoma. (2015)
  • Author(s): Yanagisawa, M., Aida, T., Takeda, T., Namekata, K., Harada, T., Shinagawa, R. and *Tanaka. K.
  • Journal Title: Cell Death and Disease Volume: 6 Issue: 3 Pages: e1693-e1693
  • DOI: 10.1038/cddis.2015.45
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 特集：網膜・視神経の保護と再生. 網膜変性疾患における神経保護. (2015)
  • Author(s): 原田高幸
  • Journal Title: 神経眼科 Volume: 32 Pages: 234-239
• [Journal Article] Valproic acid prevents retinal degeneration in a murine model of normal tension glaucoma (2015)
  • Author(s): Kimura, A., Guo, X., Noro, T., Harada, C., Tanaka, K., Namekata, K. and Harada, T
  • Journal Title: Neuroscience Letters Volume: 588 Pages: 108-113
  • DOI: 10.1016/j.neulet.2014.12.054
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Valproic acid prevents NMDA-induced retinal ganglion cell death via stimulation of neuronal TrkB receptor signaling (2015)
  • Author(s): Kimura, A., Namekata, K., Guo, X., Noro, T., Harada, C. and Harada, T.
  • Journal Title: American Journal of Pathology Volume: 185 Issue: 3 Pages: 756-764
  • DOI: 10.1016/j.ajpath.2014.11.005
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Retinoic acid receptor stimulation ameliorates experimental autoimmune optic neuritis (2014)
  • Author(s): Keino H, Watanabe T, Sato Y, Shudo K, Kitaoka Y, Harada T, Okada AA
  • Journal Title: Clin Experiment Ophthalmol Volume: 43 Issue: 6 Pages: 558-567
  • DOI: 10.1111/ceo.12308
  • Peer Reviewed
• [Journal Article] Dock3 overexpression and p38 MAPK inhibition synergistically stimulate neuroprotection and axon regeneration after optic nerve injury. (2014)
  • Author(s): Semba K, Namekata K, Kimura A, Harada C, Katome T, Yoshida H, Mitamura Y, Harada, T
  • Journal Title: Neurosci Lett Volume: 581 Pages: 89-93
  • DOI: 10.1016/j.neulet.2014.08.034
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Dock3 protects myelin in the cuprizone model for demyelination. (2014)
  • Author(s): Namekata K, Kimura A, Harada C, Yoshida H, Matsumoto Y, Harada T.
  • Journal Title: Cell Death Dis. Volume: 5 Issue: 8 Pages: e1395-e1395
  • DOI: 10.1038/cddis.2014.357
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Dock GEFs and their therapeutic potential: neuroprotection and axon regeneration. (2014)
  • Author(s): Namekata K, Kimura A, Kawamura K, Harada C, Harada T.
  • Journal Title: Prog Retin Eye Res. Volume: 43 Pages: 1-16
  • DOI: 10.1016/j.preteyeres.2014.06.005
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Neuroprotection by valproic acid and spermidine in a mouse model of normal tension glaucoma. (2015)
  • Author(s): Takayuki Harada, Atsuko Kimura, Takahiko Noro, Xiaoli Guo, Kazuhiko Namekata, Chikako Harada.
  • Organizer: 45th Annual Meeting of the Society for Neuroscience
  • Place of Presentation: Chicago, USA
  • Year and Date: 2015-10-20
  • Int'l Joint Research
• [Presentation] Brimonidine suppresses loss of retinal neurons and visual function in murine models of glaucoma and optic neuritis. (2015)
  • Author(s): Xiaoli Guo, Kazuhiko Namekata, Atsuko Kimura, Takahiko Noro, Chikako Harada, Takayuki Harada.
  • Organizer: 45th Annual Meeting of the Society for Neuroscience
  • Place of Presentation: Chicago, USA
  • Year and Date: 2015-10-19
  • Int'l Joint Research
• [Presentation] TrkB signaling in Muller glia stimulates neuroprotection after optic nerve injury. (2015)
  • Author(s): Takayuki Harada.
  • Organizer: European Association for Vision and Eye Research (EVER) 2015 Congress
  • Place of Presentation: Nice, France
  • Year and Date: 2015-10-09
  • Int'l Joint Research
• [Presentation] Mechanisms of RGC death in a murine model of normal tension glaucoma. (2015)
  • Author(s): Takayuki Harada.
  • Organizer: World Glaucoma Congress 2015
  • Place of Presentation: Hong Kong
  • Year and Date: 2015-06-07
  • Int'l Joint Research / Invited
• [Presentation] ブリモニジンの神経保護効果を極める (2015)
  • Author(s): 原田高幸.
  • Organizer: 第119回 日本眼科学会総会
  • Place of Presentation: ロイトン札幌（北海道札幌市）
  • Year and Date: 2015-04-17
  • Invited
• [Presentation] Brimonidine protects retinal neurons and visual function in a murine model of optic neuritis. (2015)
  • Author(s): Guo X., Namekata K., Kimura A., Noro T., Harada C. & Harada T.
  • Organizer: 第119回 日本眼科学会総会
  • Place of Presentation: ロイトン札幌（北海道札幌市）
  • Year and Date: 2015-04-17
• [Presentation] ブリモニジンは正常眼圧緑内障モデルマウスにおける神経変性を抑制する. (2015)
  • Author(s): 仙波賢太郎、行方和彦、木村敦子、原田知加子、三田村佳典、原田高幸.
  • Organizer: 第119回 日本眼科学会総会
  • Place of Presentation: 札幌芸文館（北海道札幌市）
  • Year and Date: 2015-04-17
• [Presentation] Dock3はERKシグナルを介して視神経の脱髄を抑制する. (2015)
  • Author(s): 行方和彦、木村敦子、郭 曉麗、原田知加子、原田高幸.
  • Organizer: 第119回 日本眼科学会総会
  • Place of Presentation: ロイトン札幌（北海道札幌市）
  • Year and Date: 2015-04-16
• [Presentation] Spermidine stimulates neuroprotection and optic nerve regeneration following optic nerve injury. (2015)
  • Author(s): Takahiko Noro , Kazuhiko Namekata, Xiaoli Guo, Atsuko Kimura, Yuriko Azuchi, Tadashi Nakano, Hiroshi Tsuneoka, Takayuki Harada.
  • Organizer: 2015 Asia-ARVO
  • Place of Presentation: パシフィコ横浜（神奈川・横浜）
  • Year and Date: 2015-02-18
• [Presentation] Valproic acid protects retinal neurons from NMDA-induced neurotoxicity via stimulation of neuronal TrkB receptors. (2015)
  • Author(s): Atsuko Kimura, Kazuhiko Namekata, Xiaoli Guo, Takahiko Noro, Chikako Harada, Takayuki Harada.
  • Organizer: 2015 Asia-ARVO
  • Place of Presentation: パシフィコ横浜（神奈川・横浜）
  • Year and Date: 2015-02-18
• [Presentation] 網膜変性疾患における神経保護. (2014)
  • Author(s): 原田高幸
  • Organizer: 第52回 日本神経眼科学会
  • Place of Presentation: 幕張メッセ（千葉・幕張）
  • Year and Date: 2014-12-12
  • Invited
• [Book] Neuroprotection and Neuroregeneration for Retinal Diseases (2014)
  • Author(s): Toru Nakazawa, Yasushi Kitaoka, Takayuki Harada, eds.
  • Total Pages: 356
  • Publisher: Springer Japan
• [Remarks] 視覚病態プロジェクト
  • URL: http://www.igakuken.or.jp/retina/
• [Remarks] 抗てんかん薬から緑内障治療薬へ ～バルプロ酸の神経保護作用メカニズムの解明～
  • URL: http://www.igakuken.or.jp/topics/2015/0319.html
• [Patent(Industrial Property Rights)] 視神経保護剤 (2015)
  • Inventor(s): 原田高幸、他
  • Industrial Property Rights Holder: 公益財団法人東京都医学総合研究所
  • Industrial Property Rights Type: 特許
  • Filing Date: 2015-04-30