Effects of ASK1 and Dock family members on the modulation of optic neuritis

• Project/Area Number: 25462766
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• 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): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 視神経炎 / ASK1 / Dock8 / Dock3 / 神経保護

Outline of Final Research Achievements

We examined the effects of ASK1, one of the stress response genes, on the severity of optic neuritis in experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. Clinical signs of EAE were mild in glia-specific ASK1 conditional knockout mice. We also examined the effect of Dock8, an atypical guanine nucleotide exchange factor, on EAE, and found that optic neuritis was mild in Dock8 deficient mice.

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] 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] 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
• [Journal Article] Dock3 attenuates neural cell death due to NMDA neurotoxicity and oxidative stress in a mouse model of normal tension glaucoma. (2013)
  • Author(s): Namekata K, Kimura A, Kawamura K, Guo X, Harada C, Tanaka K, Harada, T.
  • Journal Title: Cell Death and Differentiation Volume: 20 Issue: 9 Pages: 1250-1256
  • DOI: 10.1038/cdd.2013.91
  • Peer Reviewed
• [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 Pages: 705-706
• [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] 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（神奈川県・横浜市）
  • 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（神奈川県・横浜市）
  • Year and Date: 2015-02-18
• [Presentation] Interaction between renin-angiotensin and innate immune systems in autoimmune neuroinflammation.
  • Author(s): Xiaoli Guo, Kazuhiko Namekata, Chikako Harada, Takayuki Harada.
  • Organizer: 北米神経科学会
  • Place of Presentation: San Diego, USA
• [Presentation] Dock8 is a therapeutic target for CNS inflammation.
  • Author(s): Kazuhiko Namekata, Chikako Harada, Xiaoli Guo, Takayuki Harada.
  • Organizer: 北米神経科学会
  • Place of Presentation: San Diego, USA
• [Presentation] Roles of ASK1 in neuroprotection and axonal regeneration after optic nerve injury.
  • Author(s): Daiji Kittaka, Kazuhiko Namekata, Takuji Kurimoto, Xiaoli Guo, Chikako Harada, Takayuki Harada.
  • Organizer: 北米神経科学会
  • Place of Presentation: San Diego, USA
• [Presentation] Dock3 protects retinal neurons in a mouse model of normal tension glaucoma.
  • Author(s): Kazuhiko Namekata, Xiaoli Guo, Chikako Harada, Takayuki Harada.
  • Organizer: World Ophthalmology Congress of the International Council of Ophthalmology (WOC) 2014
  • Place of Presentation: 東京国際フォーラム
• [Presentation] Inhibition of angiotensin II ameliorates autoimmune optic neuritis by suppressing innate immune responses.
  • Author(s): Xiaoli Guo, Kazuhiko Namekata, Chikako Harada, Takayuki Harada.
  • Organizer: World Ophthalmology Congress of the International Council of Ophthalmology (WOC) 2014
  • Place of Presentation: 東京国際フォーラム
• [Presentation] Dock8/10 regulate severity of inflammatory demyelination disorder.
  • Author(s): Kazuhiko Namekata, Xiaoli Guo, Atsuko Kimura, Chikako Harada, Takayuki Harada.
  • Organizer: The ARVO (The Association for Research in Vision and Ophthalmology) 2014
  • Place of Presentation: Orland, USA
• [Presentation] Combined inhibition of angiotensin II type 1 receptor and ASK1 significantly attenuates autoimmune optic neuritis.
  • Author(s): Xiaoli Guo, Kazuhiko Namekata, Chikako Harada, Takayuki Harada.
  • Organizer: The ARVO (The Association for Research in Vision and Ophthalmology) 2014
  • Place of Presentation: Orland, USA
• [Book] Neuroprotection and Neuroregeneration for Retinal Diseases (2014)
  • Author(s): Chikako Harada, Takayuki Harada. (Toru Nakazawa, Yasushi Kitaoka, Takayuki Harada, eds)
  • Total Pages: 356
  • Publisher: Springer Japan
• [Book] Neurotrophic factors. In: Neuroprotection and Neuroregeneration for Retinal Diseases. (2014)
  • Author(s): Harada, C. and Harada, T.
  • 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/retina/topics/topics7.html
• [Remarks] 視覚病態プロジェクトの研究紹介
  • URL: http://www.igakuken.or.jp/retina/