Neuroprotection of experimental autoimmune optic neuritis by retinoid

• Project/Area Number: 23592615
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Kyorin University
• Principal Investigator: KEINO Hiroshi 杏林大学, 医学部, 准教授 (90328211)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 視神経炎 / レチノイド / 自己免疫

Research Abstract

In the present study, we investigated whether all trans-retinoic acid (ATRA) can reduce the degree of experimental autoimmune optic neuritis (EAON) in mice. Optic neuritis was induced in C57BL/6 mice by immunizing them with myelin oligodendrocyte glycoprotein35-55. ATRA (350 ug/mouse/time point) was administered every other day from day 0 to day 20. ATRA treatment significantly reduced the clinical score of EAE and the severity of the optic neuritis by histopathological analysis. The production of IFN-g and IL-17 by draining lymph node cells was significantly reduced in ATRA-treated mice. The degree of demyelination in the optic nerve of mice with EAE was significantly reduced after ATRA treatment. These findings demonstrate that ATRA treatment was able to reduce the severity of optic neuritis in mice with EAE.

Research Products

• [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] Behçet's disease ocular attack score 24: evaluation of ocular disease activity before and after initiation of infliximab. (2014)
  • Author(s): Kaburaki T, Namba K, Sonoda KH, Kezuka T, Keino H, Fukuhara T, Kamoi K, Nakai K, Mizuki N, Ohguro N; Ocular Behçet Disease Research Group of Japan
  • Journal Title: Jpn J Ophthalmol Volume: 58(2) Issue: 2 Pages: 120-130
  • DOI: 10.1007/s10384-013-0294-0
  • NAID: 40020019721
  • Peer Reviewed / Open Access
• [Journal Article] Role of IL-22- and TNF-α-producing Th22 cells in uveitis patients with Behcet's disease (2013)
  • Author(s): Sugita S, Kawazoe Y, Imai A, Kawaguchi T, Horie S, Keino H, Takahashi M, Mochizuki M
  • Journal Title: J Immunol Volume: 190 Pages: 5799-808
  • Peer Reviewed
• [Journal Article] Enhanced depth imaging optical coherence tomography of the choroid in recurrent unilateral posterior scleritis (2013)
  • Author(s): Taki W, Keino H, Watanabe T, Okada AA
  • Journal Title: Graefes Arch Clin Exp Ophthalmol Volume: 251 Issue: 3 Pages: 1003-1004
  • DOI: 10.1007/s00417-012-1972-1
  • Peer Reviewed
• [Journal Article] Enhanced depth imaging optical coherence tomography of the choroid in new-onset acute posterior scleritis (2013)
  • Author(s): Hirukawa K, Keino H, Watanabe T, Okada AA
  • Journal Title: Graefes Arch Clin Exp Ophthalmol Volume: 251 Issue: 9 Pages: 2273-2275
  • DOI: 10.1007/s00417-013-2265-z
  • Peer Reviewed
• [Journal Article] Role of IL-22- and TNF-α-producing Th22 cells in uveitis patients with Behcet's disease. (2013)
  • Author(s): Sugita S, Kawazoe Y, Imai A, Kawaguchi T, Horie S, Keino H, Takahashi M, Mochizuki M
  • Journal Title: J Immunol Volume: 190 Issue: 11 Pages: 5799-5808
  • DOI: 10.4049/jimmunol.1202677
  • Peer Reviewed
• [Journal Article] Immunosuppressive properties of regulatory T cells generated by incubation of peripheral blood mononuclear cells with supernatants of human RPE cells. (2013)
  • Author(s): Imai A, Sugita S, Kawazoe Y, Horie S, Yamada Y, Keino H, Maruyama K, Mochizuki M.
  • Journal Title: Invest Ophthalmol Vis Sci Volume: 53 Issue: 11 Pages: 7299-7309
  • DOI: 10.1167/iovs.12-10182
  • Peer Reviewed
• [Journal Article] Exudative retinal astrocytic hamartoma diagnosed and treated with pars plana vitrectomy and intravitreal bevacizumab (2012)
  • Author(s): Nakayama M, Keino H, Hirakata A, Okada AA, Terado Y
  • Journal Title: Eye Volume: 26 Issue: 9 Pages: 1272-1273
  • DOI: 10.1038/eye.2012.124
  • Peer Reviewed
• [Journal Article] Enhanced depth imaging optical coherence tomography of the choroid in Vogt-Koyanagi-Harada disease (2012)
  • Author(s): Nakayama M, Keino H, Okada AA, Watanabe T, Taki W, Inoue M, Hirakata A.
  • Journal Title: Retina Volume: 32 Issue: 10 Pages: 2061-2069
  • DOI: 10.1097/iae.0b013e318256205a
  • Peer Reviewed
• [Journal Article] Retinoic acid from retinal pigment epithelium induces T regulatory cells (2012)
  • Author(s): Kawazoe Y, Sugita S, Keino H, Yamada Y, Imai A, Horie S, Mochizuki M
  • Journal Title: Exp Eye Res Volume: 94 Issue: 1 Pages: 32-40
  • DOI: 10.1016/j.exer.2011.11.002
  • Peer Reviewed
• [Journal Article] Effect of infliximab on gene expression profiling in Behcet’s disease (2011)
  • Author(s): Keino H, Watanabe T, Taki W, Okada AA.
  • Journal Title: Invest Ophthalmol Vis Sci Volume: 52 Issue: 10 Pages: 7681-7686
  • DOI: 10.1167/iovs.11-7999
  • Peer Reviewed
• [Journal Article] Decreased ocular inflammatory attacks and background retinal and disc vascular leakage in patients with Behcet’s disease on infliximab therapy (2011)
  • Author(s): Keino H, Okada AA, WatanabeT, Taki W.
  • Journal Title: Br J Ophthalmol Volume: 95 Pages: 1245-1250
  • Peer Reviewed
• [Journal Article] クオンティフェロン(QFT)は結核性眼炎症疾患の診断に有効か？ (2011)
  • Author(s): 慶野 博
  • Journal Title: あたらしい眼科 Volume: 28 Pages: 1001-1003
• [Journal Article] 眼炎症性疾患と生物製剤 (2011)
  • Author(s): 慶野 博
  • Journal Title: 臨床眼科 Volume: 65 Pages: 372-375
• [Presentation] Retinoic acid receptor-alpha/beta-specific ligand Am80 ameliorates optic neuritis in mice with experimental autoimmune encephalomyelitis (2013)
  • Author(s): Keino H, Sato Y, Okada AA
  • Organizer: Federation of Clinical Immunology Societies (FOCIS)
  • Place of Presentation: Boston USA
• [Presentation] 難治性眼炎症疾患に対するFoxp3陽性制御性T細胞による免疫抑制療法の可能性 (2013)
  • Author(s): 慶野博
  • Organizer: 第117回日本眼科学会総会
  • Place of Presentation: 東京
• [Presentation] 難治性眼炎症疾患に対するFoxp3陽性制御性T細胞による免疫抑制療法の可能性 (2013)
  • Author(s): 慶野 博
  • Organizer: 日本眼科学会総会
  • Place of Presentation: 東京
• [Presentation] Evaluation of choroidal thickness in Vogt-Koyanagi-Harada disease andSympathetic Ophthalmia by enhanced depth imaging - OCT (EDI-OCT) (2013)
  • Author(s): Hiroshi Keino
  • Organizer: 8 th International Workshop on Vogt-Koyanagi-Harada disease and sympathetic ophthalmia
  • Place of Presentation: Kaohsiung, Taiwan
• [Presentation] IL-2/IL-2 Ab complex plus rapamycin ameliorate experimental autoimmune uveoretinitis associated with expansion of CD4+Foxp3+ regulatory T cells (2013)
  • Author(s): Hiroshi Keino, Yasuhiko Sato, and Annabelle A Okada
  • Organizer: Association for Research in Vision and Ophthalmology
  • Place of Presentation: Seattle WA, USA
• [Presentation] Retinoic acid receptor-α/β-specific ligand Am80 ameliorates optic neuritis in mice with experimental autoimmune encephalomyelitis (2013)
  • Author(s): Hiroshi Keino, Yasuhiko Sato, Annabelle A Okada
  • Organizer: Federation of Clinical Immunology Societies
  • Place of Presentation: Boston MA, USA
• [Presentation] 杏林アイセンターにおける小児および若年者のぶどう膜炎の統計 (2013)
  • Author(s): 慶野博、中島史絵、渡辺交世、瀧和歌子、岡田アナベルあやめ
  • Organizer: 第67回日本臨床眼科学会
  • Place of Presentation: 横浜
• [Presentation] 網膜動静脈閉塞症に対してステロイドパルス療法が奏功したSLE網膜症の1例 (2012)
  • Author(s): 肥留川京子、慶野博、渡辺交世、瀧和歌子、平形明人、岡田アナベルあやめ
  • Organizer: 第46回日本眼炎症学会
  • Place of Presentation: 横浜
• [Presentation] インフリキシマブ長期投与ベーチェット病患者の蛍光眼底造影像の推移 (2012)
  • Author(s): 慶野博、渡辺交世、瀧和歌子、岡田アナベルあやめ
  • Organizer: 第46回日本眼炎症学会
  • Place of Presentation: 横浜
• [Presentation] インフリキシマブ治療を導入した若年性ベーチェット病ぶどう膜網膜炎の2症例 (2012)
  • Author(s): 渡辺交世、慶野博、瀧和歌子、越前成旭、岡田アナベルあやめ
  • Organizer: 第116回日本眼科学会総会
  • Place of Presentation: 東京
• [Presentation] シンポジウム12眼炎症疾患のメカニズム最前線レチノイドによる眼炎症性疾患の制御 (2012)
  • Author(s): 慶野博
  • Organizer: 第116回日本眼科学会総会
  • Place of Presentation: 東京
• [Presentation] レチノイドによる眼炎症性疾患の制御 (2012)
  • Author(s): 慶野 博
  • Organizer: 第116回日本眼科学会総会
  • Place of Presentation: 東京
• [Presentation] EDI-OCTを用いた交感性眼炎回復期の脈絡膜厚の評価 (2012)
  • Author(s): 慶野博、渡辺交世、瀧 和歌子、岡田アナベルあやめ
  • Organizer: 第66回日本臨床眼科学会
  • Place of Presentation: 京都
• [Presentation] 病診連携から考えるぶどう膜炎の診断と治療、合併症（続発緑内障）への対応 (2012)
  • Author(s): 慶野博
  • Organizer: 調布市眼科医会学術講演会(招待講演)
  • Place of Presentation: 東京
• [Presentation] Effect of infliximab on inflammation-related gene expression in Behcet's disease (2011)
  • Author(s): Keino H
  • Organizer: IOIS
  • Place of Presentation: Goa India
• [Presentation] EDI-OCTを用いた原田病回復期の脈絡膜厚の評価 (2011)
  • Author(s): 慶野博、渡辺交世、中山真紀子、瀧和歌子、岡田アナベルあやめ
  • Organizer: 第65回日本臨床眼科学会
  • Place of Presentation: 東京
• [Presentation] Effect of infliximab on inflammation-related gene expression in Behcet's disease (2011)
  • Author(s): Keino H
  • Organizer: 第115回日本眼科学会総会
  • Place of Presentation: 東京
• [Presentation] Bevacizumab硝子体注射により新生血管の退縮がみられた転移性虹彩腫瘍の1例. (2011)
  • Author(s): 中島史絵、慶野博、渡邊交世、瀧和歌子、岡田アナベルあやめ.
  • Organizer: 第115回日本眼科学会総会
  • Place of Presentation: 東京
• [Presentation] Application of research tools in clinical disease Effect of infliximab on inflammation-related gene expression in Behcet’s disease (2011)
  • Author(s): Hiroshi Keino
  • Organizer: 第115回日本眼科学会総会 ARVO/JOS(招待講演)
  • Place of Presentation: 東京
• [Presentation] Enhanced depth imaging optical coherence tomography of the choroid in new-onset acute Vogt-Koyanagi-Harada disease. (2011)
  • Author(s): Nakayama M, Keino H, Watanabe T, Inoue M, Hirakata A, Okada AA.
  • Organizer: ARVO
  • Place of Presentation: Ft. Lauderdale, Florida, USA
• [Presentation] 原田病における脈絡膜厚の長期経過. (2011)
  • Author(s): 中山真紀子、慶野 博、渡邊交世、瀧和歌子、岡田アナベルあやめ.
  • Organizer: 第45回日本眼炎症学会
  • Place of Presentation: 京都
• [Presentation] EDI-OCTを用いた片眼性後部強膜炎の脈絡膜厚の評価. (2011)
  • Author(s): 瀧和歌子、慶野博、渡辺交世、伊東真知子、岡田アナベルあやめ.
  • Organizer: 第45回日本眼炎症学会
  • Place of Presentation: 京都
• [Presentation] 結節性硬化症に合併した網膜腫瘍に網膜生検を施行した一例. (2011)
  • Author(s): 中山真紀子、平形明人、慶野博、柴田朋宏、寺戸雄一、藤野節、岡田アナベルあやめ.
  • Organizer: 第65回日本臨床眼科学会
  • Place of Presentation: 東京
• [Presentation] 眼炎症疾患に伴う黄斑浮腫に対する炭酸脱水素酵素阻害剤内服投与の有効性の再考. (2011)
  • Author(s): 渡辺交世、慶野博、瀧和歌子、越前成旭、岡田アナベルあやめ.
  • Organizer: 第65回日本臨床眼科学会
  • Place of Presentation: 東京
• [Presentation] EDI-OCTを用いた原田病回復期の脈絡膜厚の評価. (2011)
  • Author(s): 慶野博、渡辺交世、中山真紀子、瀧和歌子、岡田アナベルあやめ.
  • Organizer: 第65回日本臨床眼科学会
  • Place of Presentation: 東京
• [Presentation] Oral administration of retinoic acid receptor-a/b specific ligand, Am80 suppresses experimental autoimmune uveoretinitis (2011)
  • Author(s): Oral administration of retinoic acid receptor-α/β specific ligand, Am80 suppresses experimental autoimmune uveoretinitis
  • Organizer: The Asia Pacific Meeting of Vasculitis and ANCA Workshop 2012
  • Place of Presentation: 東京
• [Book] Monthly Book OCULISTA No.5ぶどう膜炎外来診療ぶどう膜炎の眼科検査所見 (2013)
  • Author(s): 慶野博
  • Publisher: 全日本病院出版会
• [Book] Monthly Book OCULISTA No.5 ぶどう膜炎 外来診療 (2013)
  • Author(s): 慶野 博
  • Total Pages: 8
  • Publisher: 全日本病院出版会
• [Book] 眼科疾患ビジュアルブック (2013)
  • Author(s): 慶野 博
  • Total Pages: 19
  • Publisher: 学研メディカル秀潤社
• [Book] 眼科臨床エキスパート 所見から考えるぶどう膜炎 (2013)
  • Author(s): 慶野 博
  • Total Pages: 8
  • Publisher: 医学書院
• [Book] 眼科疾患最新の治療2013-2015 (2013)
  • Author(s): 慶野 博
  • Total Pages: 2
  • Publisher: 南江堂
• [Book] 眼科診療のピットフォール (2013)
  • Author(s): 慶野 博
  • Total Pages: 4
  • Publisher: 金芳堂
• [Book] 分子標的治療薬とぶどう膜炎治療専門医のための眼科診療クオリファイ13ぶどう膜炎を斬る (2012)
  • Author(s): 慶野博
  • Publisher: 中山書店
• [Book] リウマチから学ぶ各種TNF阻害治療薬の使い方とぶどう膜炎への応用専門医のための眼科診療クオリファイ13ぶどう膜炎を斬る (2012)
  • Author(s): 慶野博
  • Publisher: 中山書店
• [Book] ぶどう膜炎診療の話題Vogt-小柳-原田病の画像診断 (2012)
  • Author(s): 慶野博
  • Publisher: Ophthalmic Foresight (vol17 No3)
• [Book] 専門医のための眼科診療クオリファイ 13 ぶどう膜炎を斬る (2012)
  • Author(s): 慶野 博
  • Total Pages: 13
  • Publisher: 中山書店
• [Book] 眼科疾患ビジュアルブックChapter 8強膜疾患強膜炎、上強膜炎, Chapter 12後眼部疾患・ぶどう膜炎
  • Author(s): 慶野博