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Roles of AMP-activated protein kinase in diabetes-induced retinal inflammation.

Research Project

Project/Area Number 24592649
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Ophthalmology
Research InstitutionKeio University

Principal Investigator

MOCHIMARU Hiroshi  慶應義塾大学, 医学部, 助教 (90424168)

Co-Investigator(Kenkyū-buntansha) NAGAI Norihiro  慶應義塾大学, 医学部, 助教 (10327611)
OZAWA Yoko  慶應義塾大学, 医学部, 講師 (90265885)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords網膜 / 糖尿病 / 炎症 / 細胞・組織
Outline of Final Research Achievements

The streptozotocin-induced diabetes were treated with resveratrol orally at 50 mg/kg for 7 days or with AICAR intraperitoneally at 100 mg/kg 24 hours before death. Induction of diabetes in mice led to retinal AMPK dephosphorylation, which was significantly reversed by either resveratrol or AICAR. Either resveratrol or AICAR significantly reversed SIRT1 deactivation and NF-κB phosphorylation, both of which were induced in the diabetic retina. Administration of resveratrol to diabetic mice significantly reduced diabetes-induced retinal leukocyte adhesion, together with retinal expression of ICAM-1 and VEGF. The present findings reveal that diabetes-induced retinal inflammation stems from downregulation of the AMPK pathway, leading subsequently to SIRT1 deactivation and NF-κB activation. The data also suggest the potential use of the AMPK activator resveratrol as a therapeutic agent for diabetic retinopathy.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (14 results)

All 2015 2014 2013 2012 Other

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 3 results,  Acknowledgement Compliant: 2 results) Presentation (9 results)

  • [Journal Article] Association of macular pigment optical density with serum concentration of oxidized low-density lipoprotein in healthy adults.2015

    • Author(s)
      Nagai N, Izumi-Nagai K, Suzuki M, Shinoda H, Koto T, Uchida A, Mochimaru H, Tomita Y, Miyake S, Kobayashi S, Sasaki M, Tsubota K, Ozawa Y.
    • Journal Title

      Retina

      Volume: 35(4) Issue: 4 Pages: 820-826

    • DOI

      10.1097/iae.0000000000000382

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Association of Maternal Age to Development and Progression of Retinopathy of Prematurity in Infants of Gestational Age under 33 Weeks.2014

    • Author(s)
      Uchida A, Miwa M, Shinoda H, Koto T, Nagai N, Mochimaru H, Tomita Y, Sasaki M, Ikeda K, Tsubota K, Ozawa Y
    • Journal Title

      J Ophthalmol.

      Volume: 2014 Pages: 187929-187929

    • DOI

      10.1155/2014/187929

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Ozawa Predictive factors for non-responders to intravitreal ranibizumab treatment in age-related macular degeneration2014

    • Author(s)
      Suzuki M, Nagai N, Izumi-Nagai K, Shinoda H, Koto T, Uchida A, Mochimaru H, Yuki K, Sasaki M, Tsubota K
    • Journal Title

      Br J Ophthalmol

      Volume: 98 Issue: 9 Pages: 7-7

    • DOI

      10.1136/bjophthalmol-2013-304670

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Vitrectomy for myopic foveoschisis with internal limiting membrane peeling and no gas tamponade.2013

    • Author(s)
      Uchida A, Shinoda H, Koto T, Mochimaru H, Nagai N, Tsubota K, Ozawa Y
    • Journal Title

      Retina.

      Volume: 34 Issue: 3 Pages: 455-460

    • DOI

      10.1097/iae.0b013e3182a0e477

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Detection of Early Visual Impairment in Patients with Epiretinal Membrane.2013

    • Author(s)
      Nishi Y, Shinoda H, Uchida A, Koto T, Mochimaru H, Nagai N, Tsubota K, Ozawa Y.
    • Journal Title

      Acta Ophthalmologica

      Volume: Epub ahead of print Issue: 5 Pages: 1-5

    • DOI

      10.1111/aos.12060

    • Related Report
      2013 Research-status Report 2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 治療抵抗性の加齢黄斑変性に対するアフリベルセプトスイッチング症例の1年成績2014

    • Author(s)
      永井紀博、鈴木美砂、持丸博史、富田洋平、内田敦郎、栗原俊秀、佐々木真理子、篠田肇、坪田一男、小沢洋子.
    • Organizer
      第53回日本網膜硝子体学会総会
    • Place of Presentation
      大阪国際会議場(大阪府大阪市)
    • Year and Date
      2014-11-28 – 2014-11-30
    • Related Report
      2014 Annual Research Report
  • [Presentation] 多局所網膜電図を施行したfocal choroidal excavation 3例2014

    • Author(s)
      内田敦郎、富田洋平、持丸博史、栗原俊英、永井紀博、篠田肇、小沢洋子、坪田一男.
    • Organizer
      第53回日本網膜硝子体学会総会
    • Place of Presentation
      大阪国際会議場(大阪府大阪市)
    • Year and Date
      2014-11-28 – 2014-11-30
    • Related Report
      2014 Annual Research Report
  • [Presentation] 網膜静脈分枝閉塞症に伴う黄斑浮腫に対するラニビズマブ投与の3カ月治療成績.2014

    • Author(s)
      栗原俊英、永井紀博、鈴木美砂、内田敦郎、持丸博史、富田洋平、篠田肇、坪田一男、小沢洋子.
    • Organizer
      第68回日本臨床眼科学会
    • Place of Presentation
      神戸国際展示場(兵庫県神戸市)
    • Year and Date
      2014-11-13 – 2014-11-16
    • Related Report
      2014 Annual Research Report
  • [Presentation] 無治療のポリープ状脈絡膜血管症に対するラニビズマブ、アフリベルセプトの作用2014

    • Author(s)
      伊吹麻里、永井紀博、鈴木美砂、富田洋平、持丸博史、栗原俊英、内田敦郎、篠田肇、坪田一男、小沢洋子.
    • Organizer
      第68回日本臨床眼科学会
    • Place of Presentation
      神戸国際展示場(兵庫県神戸市)
    • Year and Date
      2014-11-13 – 2014-11-16
    • Related Report
      2014 Annual Research Report
  • [Presentation] A Case of Corneal Infiltration after intravitreal Injection of Bevacizumab.2014

    • Author(s)
      Ozawa N, Nagai N, Mochimaru H, Tsubota K, Ozawa Y.
    • Organizer
      World Ophthalmology Congress 2014
    • Place of Presentation
      東京国際フォーラム(東京都千代田区)
    • Year and Date
      2014-04-02 – 2014-04-06
    • Related Report
      2014 Annual Research Report
  • [Presentation] 狭義加齢黄斑変性に対するpro re nateによるラニビズマブ硝子体注射.2013

    • Author(s)
      3. 鈴木美砂, 永井紀博, 永井香奈子, 篠田肇, 内田敦郎, 厚東隆志, 持丸博史, 富田洋平, 佐々木真理子, 坪田一男, 小沢洋子.
    • Organizer
      第67回日本臨床眼科学会
    • Place of Presentation
      パシフィコ横浜 神奈川県 横浜市
    • Related Report
      2013 Research-status Report
  • [Presentation] 新規過活動膀胱治療薬ミラベグロン投与後早期に発症した網膜静脈分子閉塞症の一例2012

    • Author(s)
      持丸博史、前田高宏、厚東隆志、内田敦郎、永井紀博、篠田肇、坪田一男、小沢洋子
    • Organizer
      第66回日本臨床眼科学会総会
    • Place of Presentation
      京都府京都市
    • Related Report
      2012 Research-status Report
  • [Presentation] Associations of Serum Lipids with Macular Morphology in Patients without Diabetic Macular Edema.

    • Author(s)
      Sasaki M, Kawashima M, Kawasaki R, Kawai M, Uchida A, Koto T, Mochimaru H, Shinoda H, Jie Jin Wang, Tsubota K, Ozawa Y.
    • Organizer
      Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting
    • Place of Presentation
      Washington State Convention & Trade Center Seattle, USA,
    • Related Report
      2013 Research-status Report
  • [Presentation] Baseline characteristics and response to intravitreal ranibizumab therapy for age-related macular degeneration.

    • Author(s)
      Suzuki M, Nagai N, Izumi-Nagai K, Shinoda H, Koto T, Uchida A, Mochimaru H, Yuki K, Tsubota K, Ozawa Y.
    • Organizer
      Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting
    • Place of Presentation
      Washington State Convention & Trade Center Seattle, USA,
    • Related Report
      2013 Research-status Report

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Published: 2013-05-31   Modified: 2019-07-29  

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