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Basis for chronobiological approach in treatment of corneal nerve damage

Research Project

Project/Area Number 26861456
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Ophthalmology
Research InstitutionOita University

Principal Investigator

Kusunose Naoki  大分大学, 医学部, 特任助教 (10725964)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords体内時計 / 時計遺伝子 / マイトマイシンC / グルココルチコイド / 神経障害
Outline of Final Research Achievements

Mitomycin C (MMC), which has been applied in surgery of glaucoma or pterygium to suppress growth of fibroblasts, could induce corneal nerve damage. Circadian rhythm of physiological function is regulated by particular gene cluster called as clock gene, which is component of molecular clock. In this study, we performed in vitro study to clarify the possibility of MMC induced dysfunction of circadian clock and relationship between circadian clock dysfunction and corneal nerve damage. The mouse fibroblast cell line NIH3T3 or primary fibroblasts from Per2::Luc knock in mice were used for experiments. MMC decreased expression of glucocorticoid receptor and modulated circadian oscillation of Per2::Luc bioluminescence. These results suggest that MMC could persistently modulate the circadian clock system in fibroblast of eyes.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (14 results)

All 2016 2015 2014

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (10 results) (of which Int'l Joint Research: 3 results,  Invited: 3 results)

  • [Journal Article] Dosing time-dependent changes in the analgesic effect of pregabalin on diabetic neuropathy in mice.2015

    • Author(s)
      Akamine T, Koyanagi S, Kusunose N, Hashimoto H, Taniguchi M, Matsunaga N, Ohdo S.
    • Journal Title

      Journal of Pharmacology and Experimental Therapeutics

      Volume: 354 Issue: 1 Pages: 65-72

    • DOI

      10.1124/jpet.115.223891

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mitomycin C modulates the circadian oscillation of clock gene period 2 expression through attenuating the glucocorticoid signaling in mouse fibroblasts.2015

    • Author(s)
      Kusunose N, Matsunaga N, Kimoto K, Akamine T, Hamamura K, Koyanagi S, Ohdo S, Kubota T.
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 467 Issue: 1 Pages: 157-163

    • DOI

      10.1016/j.bbrc.2015.09.086

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Modulation of peroxisome proliferator-activated receptor-α activity by bile acids causes circadian changes in the intestinal expression of Octn1/Slc22a4 in mice.2015

    • Author(s)
      Wada E, Koyanagi S, Kusunose N, Akamine T, Masui H, Hashimoto H, Matsunaga N, Ohdo S.
    • Journal Title

      Mol Pharmacol

      Volume: 87 Issue: 2 Pages: 314-322

    • DOI

      10.1124/mol.114.094979

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Bile acid-regulated peroxisome proliferator-activated receptor-α (PPARα) activity underlies circadian expression of intestinal peptide absorption transporter PepT1/Slc15a1.2014

    • Author(s)
      Okamura A, Koyanagi S, Dilxiat A, Kusunose N, Chen JJ, Matsunaga N, Shibata S, Ohdo S.
    • Journal Title

      J Biol Chem.

      Volume: 289(36) Issue: 36 Pages: 25296-25305

    • DOI

      10.1074/jbc.m114.577023

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 時間生物学的視点から迫る、糖尿病関連眼疾患の病態2016

    • Author(s)
      楠瀬直喜
    • Organizer
      第4回大分糖尿病眼合併症セミナー
    • Place of Presentation
      レンブラントホテル (大分県, 大分市)
    • Year and Date
      2016-02-13
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] マイトマイシンCによる線維芽細胞の時計遺伝子発現変容と そのメカニズムの解明2015

    • Author(s)
      楠瀬直喜、松永直哉、小柳悟、木許賢一、大戸茂弘、久保田敏昭
    • Organizer
      第22回日本時間生物学会学術大会
    • Place of Presentation
      東京大学本郷キャンパス伊藤国際学術研究センター (東京都, 文京区)
    • Year and Date
      2015-11-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] Alteration of the circadian clock system by mitomycin C in fibroblast2015

    • Author(s)
      Naoki KUSUNOSE, Naoya MATSUNAGA, Satoru KOYANAGI, Kenichi KIMOTO, Shigehiro OHDO, Toshiaki KUBOTA
    • Organizer
      The 8th Joint Meeting of Korea-China-Japan Ophthalmologists
    • Place of Presentation
      ヒルトン福岡シーホーク (福岡県, 福岡市)
    • Year and Date
      2015-10-17
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] マイトマイシンCによる線維芽細胞の時計遺伝子発現変容と そのメカニズムの解明2015

    • Author(s)
      楠瀬直喜、松永直哉、小柳悟、木許賢一、大戸茂弘、久保田敏昭
    • Organizer
      第26回日本緑内障学会
    • Place of Presentation
      ウインクあいち (愛知県, 名古屋市)
    • Year and Date
      2015-09-11
    • Related Report
      2015 Annual Research Report
  • [Presentation] Alteration of clock gene expression by mitomycin C in fibroblast2015

    • Author(s)
      Naoki KUSUNOSE, Naoya MATSUNAGA, Satoru KOYANAGI, Kenichi KIMOTO, Shigehiro OHDO, and Toshiaki KUBOTA
    • Organizer
      EBRS/WCC Meeting 2015
    • Place of Presentation
      イギリス (マンチェスター)
    • Year and Date
      2015-08-02
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Effect of mitomycin C on molecular clock system in fibroblast2015

    • Author(s)
      Naoki KUSUNOSE, Naoya MATSUNAGA, Satoru KOYANAGI, Satoko NAKANO, Shigehiro OHDO, Toshiaki KUBOTA
    • Organizer
      The 6th World Glaucoma Congress
    • Place of Presentation
      中国 (香港)
    • Year and Date
      2015-06-06
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 眼科疾患の新規治療法の開発にむけた時間生物学的研究2015

    • Author(s)
      楠瀬直喜
    • Organizer
      第85回九州眼科学会
    • Place of Presentation
      鹿児島県医師会館 (鹿児島県, 鹿児島市)
    • Year and Date
      2015-05-29
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 体内時計に着目したミューラー細胞におけるVEGFの発現制御機構の解明2015

    • Author(s)
      楠瀬直喜、中野聡子、木許賢一、久保田敏昭
    • Organizer
      第119回日本眼科学会総会
    • Place of Presentation
      ロイトン札幌/さっぽろ芸術文化の館/札幌市教育文化会館 (北海道, 札幌市)
    • Year and Date
      2015-04-16
    • Related Report
      2015 Annual Research Report
  • [Presentation] グルココルチコイドによる神経障害性疼痛の概日リズム制御2014

    • Author(s)
      楠瀬直喜、小柳悟、松永直哉、大戸茂弘
    • Organizer
      第21回日本時間生物学会学術大会
    • Place of Presentation
      九州大学医学部百年講堂 (福岡県福岡市)
    • Year and Date
      2014-11-07 – 2014-11-09
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] In vitro study concerning the alteration effect of mitomycin C on clock gene expression in fibroblast2014

    • Author(s)
      Naoki KUSUNOSE, Satoko NAKANO, Toshiaki KUBOTA
    • Organizer
      The 7th Joint Meeting of Korea-China-Japan Ophthalmologists in conjunction
    • Place of Presentation
      KINTEX (韓国ソウル)
    • Year and Date
      2014-10-31 – 2014-11-02
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2017-05-10  

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