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Involvement of Th cells in diabetic retinopathy and understanding of the Th-cell mediated pathogenic mechanisms

Research Project

Project/Area Number 16K11337
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Ophthalmology
Research InstitutionNational Defense Medical College

Principal Investigator

Takeuchi Masaru  防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 眼科学, 教授 (40260939)

Co-Investigator(Kenkyū-buntansha) 櫻井 裕  防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 衛生学公衆衛生学, 教授 (00235227)
佐藤 智人  防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 眼科学, 助教 (00724246)
伊藤 正孝  防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 再生発生学, 准教授 (30534896)
播本 幸三  防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 眼科学, 助教 (80626804)
櫻井 裕  防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究施設、病院並びに防衛, 眼科学, 助教 (10338816)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords糖尿病網膜症 / Th17細胞 / 獲得免疫 / T細胞 / 慢性炎症 / 糖尿病 / IL-17A / 増殖糖尿病網膜症 / 老化T細胞 / IL-17
Outline of Final Research Achievements

We measured IL-4, IL-17A, IL-22, IL-31, and TNFα in aqueous humors and vitreous fluids of patients with proliferative diabetic retinopathy (PDR), and examined their relevance. Although IL-17A was the most detected in the aqueous humor among these cytokines, it was significantly lower in both concentration and detection rate compared to that in the vitreous humor, and was not suitable as a marker for intravitreal IL-17A which reflects the pathological condition of PDR. On the other hand, it was shown that a new DR mouse model in which Akita mice that spontaneously develop diabetes were back-crossed to Th2 and Th17 cell dominant IFN-γ deficient mice induced much more severe DR than Akita mice.

Academic Significance and Societal Importance of the Research Achievements

本研究で解析したサイトカインでは臨床応用可能な成果はみられなかったが、DRの重症度を簡易かつ反復性に採取可能な眼の前房水により定量的に評価することができれば、DRに対する血糖コントロール、網膜光凝固治療の適応、有効性を適宜、包括的に判定することが可能になる.また、DRの進行に最も相関するサイトカインを同定できれば、血管内皮増殖因子(vascular endothelial growth factor: VEGF)以外の分子標的療法の開発に繋がることが期待される.

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (15 results)

All 2019 2018 2017

All Journal Article (11 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 6 results,  Open Access: 6 results) Presentation (4 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] Real-world evidence of treatment for relapse of noninfectious uveitis in tertiary centers in Japan2019

    • Author(s)
      Takeuchi Masaru、Kanda Takayuki、Kaburaki Toshikatsu、Tanaka Rie、Namba Kenichi、Kamoi Koju、Maruyama Kazuichi、Shibuya Etsuko、Mizuki Nobuhisa
    • Journal Title

      Medicine

      Volume: 98 Issue: 9 Pages: e14668-e14668

    • DOI

      10.1097/md.0000000000014668

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Protective effects of dexamethasone on hypoxia-induced retinal edema in a mouse model2019

    • Author(s)
      Inada Makoto、Taguchi Manzo、Harimoto Kohzou、Karasawa Yoko、Takeuchi Masaru、Ito Masataka
    • Journal Title

      Experimental Eye Research

      Volume: 178 Pages: 82-90

    • DOI

      10.1016/j.exer.2018.09.014

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinical preferences and trends of anti-vascular endothelial growth factor treatments for diabetic macular edema in Japan2018

    • Author(s)
      Sugimoto Masahiko、Tsukitome Hideyuki、Okamoto Fumiki、Oshika Tetsuro、Ueda Tetsuo、Niki Masanori、Mitamura Yoshinori、Ishikawa Hiroto、Gomi Fumi、Kitano Shigehiko、Noma Hidetaka、Shimura Masahiko、Sonoda Shozo、Sawada Osamu、Ohji Masahito、Harimoto Kozo、Takeuchi Masaru、Takamura Yoshihiro、Kondo Mineo、Sakamoto Taiji
    • Journal Title

      Journal of Diabetes Investigation

      Volume: 10 Issue: 2 Pages: 475-483

    • DOI

      10.1111/jdi.12929

    • NAID

      120006980552

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Assessment of diagnostic and therapeutic vitrectomy for vitreous opacity associated with uveitis with various etiologies2018

    • Author(s)
      Sato T, Kinoshita R, Taguchi M, Sugita S, Kaburaki T, Sakurai Y, Takeuchi M
    • Journal Title

      Medicine (Baltimore).

      Volume: 97(2) Issue: 2 Pages: e9491-e9491

    • DOI

      10.1097/md.0000000000009491

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Topical Corticosteroid-Resolved Rubeosis Iridis with Neovascular Glaucoma Caused by Noninfectious Granulomatous Uveitis2018

    • Author(s)
      Sora Daisuke、Takayama Kei、Taguchi Manzo、Sato Tomohito、Sakurai Yutaka、Kanda Takayuki、Takeuchi Masaru
    • Journal Title

      Case Reports in Ophthalmology

      Volume: 9 Issue: 1 Pages: 243-247

    • DOI

      10.1159/000488137

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Intraocular inflammatory cytokines in patients with neovascular age-related macular degeneration before and after initiation of intravitreal injection of anti-VEGF inhibitor2018

    • Author(s)
      Sato Tomohito、Takeuchi Masaru、Karasawa Yoko、Enoki Toshio、Ito Masataka
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1

    • DOI

      10.1038/s41598-018-19594-6

    • Related Report
      2017 Research-status Report
  • [Journal Article] Associations between <em>CRYBA4 </em>gene variants and high myopia in a Japanese population2017

    • Author(s)
      Kawagoe Tatsukata、Ota Masao、Meguro Akira、Takeuchi Masaki、Yamane Takahiro、Shimazaki Haruna、Takeuchi Masaru、Okada Eiichi、Teshigawara Takeshi、Mizuki Nobuhisa
    • Journal Title

      Clinical Ophthalmology

      Volume: Volume 11 Pages: 2151-2156

    • DOI

      10.2147/opth.s146038

    • Related Report
      2017 Research-status Report
  • [Journal Article] Comparison of intraocular pressure-lowering effects of ripasudil hydrochloride hydrate for inflammatory and corticosteroid-induced ocular hypertension2017

    • Author(s)
      Yasuda Mami、Takayama Kei、Kanda Takayuki、Taguchi Manzo、Someya Hideaki、Takeuchi Masaru
    • Journal Title

      PLOS ONE

      Volume: 12 Issue: 10 Pages: 0185305-0185316

    • DOI

      10.1371/journal.pone.0185305

    • Related Report
      2017 Research-status Report
    • Open Access
  • [Journal Article] Association between aqueous humor and vitreous fluid levels of Th17 cell-related cytokines in patients with proliferative diabetic retinopathy2017

    • Author(s)
      Takeuchi Masaru、Sato Tomohito、Sakurai Yutaka、Taguchi Manzo、Harimoto Kozo、Karasawa Yoko、Ito Masataka
    • Journal Title

      PLOS ONE

      Volume: 12 Issue: 5 Pages: 0178230-0178243

    • DOI

      10.1371/journal.pone.0178230

    • Related Report
      2017 Research-status Report
  • [Journal Article] Disseminated cutaneous nocardiosis with ocular involvement.2017

    • Author(s)
      Nishizawa A, Hirose M, Nagata Y, Takeuchi M, Satoh T.
    • Journal Title

      J Eur Acad Dermatol Venereol.

      Volume: 31 Issue: 11 Pages: 488-489

    • DOI

      10.1111/jdv.14328

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Anti-VEGF therapy for central retinal vein occlusion caused by tuberculosis-associated uveitis: a case report2017

    • Author(s)
      Taguchi Manzo、Sakurai Yutaka、Kanda Takayuki、Takeuchi Masaru
    • Journal Title

      International Medical Case Reports Journal

      Volume: Volume 10 Pages: 139-141

    • DOI

      10.2147/imcrj.s128885

    • Related Report
      2017 Research-status Report
  • [Presentation] 増殖糖尿病網膜症患者における房水中の炎症性サイトカインと房水フレア値との相関2018

    • Author(s)
      藤田 雄己, 佐藤 智人, 染谷 秀彬, 高山 圭, 唐澤 容子, 竹内 大
    • Organizer
      日本眼科学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 眼サルコイドーシスおよび増殖糖尿病網膜症の硝子体中におけるオステオポンチンの解析2018

    • Author(s)
      竹内 大, 佐藤 智人, 藤田 雄己, 北村 力, 唐澤 容子, 桜井 裕
    • Organizer
      日本眼科学会総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Association of Th17-cell related cytokines between Aqueous Humor and Vitreous Fluid in Proliferative Diabetic Retinopathy Patients2017

    • Author(s)
      Masaru Takeuchi, Tomohito Sato, Manzo Taguchi, Yoko Karasawa, Yutaka Sakurai, Kozo Harimoto, Masataka Ito
    • Organizer
      The Association for Research in Vision and Ophthalmology (ARVO)
    • Place of Presentation
      米国
    • Year and Date
      2017-05-07
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] IL-17A-Related Cytokines in Ocular Fluids of Proliferative Diabetic Retinopathy2017

    • Author(s)
      Masaru Takeuchi, Tomohito Sato, Manzo Taguchi, Yoko Karasawa, Yutaka Sakurai, Kozo Harimoto, Masataka Ito
    • Organizer
      第121回日本眼科学会総会
    • Place of Presentation
      日本
    • Year and Date
      2017-04-06
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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