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Analysis of blood-retinal barrier based on circadian expression of drug transporters.

Research Project

Project/Area Number 17H06976
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field Ophthalmology
Research InstitutionOita University

Principal Investigator

AKAMINE TAKAHIRO  大分大学, 医学部, 特任助教 (60799435)

Project Period (FY) 2017-08-25 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords眼科薬理学 / 時間薬理学 / トランスポーター / 血液網膜関門
Outline of Final Research Achievements

The retina has a barrier function called the blood-retinal barrier that restricts the transport of drugs from circulating blood. Drug treatment of eye disease by oral and intravenous administration is difficult. A number of drug transporters are expressed at the blood-retinal barrier, and these are considered to be one of the factors controlling drug transport from circulating blood to the retina. In this study, we examined retinal pigment epithelial cells that constitute the blood-retinal barrier. As a result, the circadian expression of transporters contributing to drug excretion was observed. Furthermore, it was shown that the cellular uptake of valproic acid, for which the neuroprotective action of the retina has been reported, also varies with time.

Academic Significance and Societal Importance of the Research Achievements

本研究結果から循環血液から網膜への薬物輸送に時刻による変動が認められることが示唆された。投与時刻を最適化するという非常に簡便な手法で薬物の治療効果を高めることが期待できる。また、眼の副作用がある薬物は眼に移行しにくい時間帯に投与することで視機能の異常を回避できる可能性がある。近年では、医師主導のサプリメントによる健康維持の気運が高まっている。循環血液から網膜へ物質が移行しやすい時間帯、移行しにくい時間帯があることが示唆されたため、ビタミンAに代表される眼に必須の栄養素のサプリメントを飲む時刻にも最適な時刻があり、今後それらの時刻を明らかにすることで視機能の健康維持にも貢献できる。

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Annual Research Report
  • Research Products

    (4 results)

All 2018

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

  • [Journal Article] Accumulation of sorbitol in the sciatic nerve modulates circadian properties of diabetes-induced neuropathic pain hypersensitivity in a diabetic mouse model2018

    • Author(s)
      Akamine Takahiro、Kusunose Naoki、Matsunaga Naoya、Koyanagi Satoru、Ohdo Shigehiro
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 503 Issue: 1 Pages: 181-187

    • DOI

      10.1016/j.bbrc.2018.05.209

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Contribution of the clock gene DEC2 to VEGF mRNA upregulation by modulation of HIF1α protein levels in hypoxic MIO-M1 cells, a human cell line of retinal glial (M?ller) cells2018

    • Author(s)
      Kusunose Naoki、Akamine Takahiro、Kobayashi Yoshiyuki、Yoshida Shigeo、Kimoto Kenichi、Yasukochi Sai、Matsunaga Naoya、Koyanagi Satoru、Ohdo Shigehiro、Kubota Toshiaki
    • Journal Title

      Japanese Journal of Ophthalmology

      Volume: 62 Issue: 6 Pages: 677-685

    • DOI

      10.1007/s10384-018-0622-5

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mutation of the gene encoding the circadian clock component PERIOD2 in oncogenic cells confers chemoresistance by up-regulating the Aldh3a1 gene2018

    • Author(s)
      Katamune Chiharu、Koyanagi Satoru、Hashikawa Ken-ichi、Kusunose Naoki、Akamine Takahiro、Matsunaga Naoya、Ohdo Shigehiro
    • Journal Title

      Journal of Biological Chemistry

      Volume: 294 Issue: 2 Pages: 547-558

    • DOI

      10.1074/jbc.ra118.004942

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] The clock gene DEC2 contributes to VEGF upregulation by modulating HIF1α protein levels in hypoxic MIO-M1 cells, a human cell line of retinal glial (Muller) cells.2018

    • Author(s)
      Takahiro AKAMINE, Naoki KUSUNOSE, Yoshiyuki KOBAYASHI, Shigeo YOSHIDA, Naoya MATSUNAGA, Satoru KOYANAGI, Kenichi KIMOTO, Shigehiro OHDO, and Toshiaki KUBOTA
    • Organizer
      The 11th Joint Meeting of Japan-China-Korea Ophthalmologists
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research

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Published: 2017-08-25   Modified: 2020-03-30  

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