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Effect of a Sema3A inhibitor treatment in a murine dry eye model

Research Project

Project/Area Number 16K11299
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Ophthalmology
Research InstitutionFujita Health University (2018)
National Institutes of Biomedical Innovation, Health and Nutrition (2017)
Keio University (2016)

Principal Investigator

Satoru Yoshida  藤田医科大学, 医学部, 講師 (50398781)

Co-Investigator(Kenkyū-buntansha) 榛村 重人  慶應義塾大学, 医学部(信濃町), 准教授 (00235780)
Research Collaborator TSUBOTA kazuo   (40163878)
OKANO hideyuki   (60160694)
YAMAZOE katsuya  
YAMAZAKI risa  
SHIMIZU shota  
YASUDA miyuki   (80574912)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords角膜神経再生 / Semaphorin3A / ドライアイ / 角膜 / 神経再生 / Semaphorin / 眼細胞生物学
Outline of Final Research Achievements

Semaphorin 3A (Sema3A) is expressed in corneal epithelium and is known to act as a repellent for axonal growth of neurons. In dry eye disease (DED), corneal nerves, which responsible for corneal sensations and tear secretion, are compromised. Therefore, inhibition of Sema3A may protect corneal nerve dysfunction in DED. Using a murine dry eye model, which developed by removing an extra-orbital lacrimal gland, we found that topical application of a selective Sema3A inhibitor, vinaxanthone, prevent disruption of corneal nerves, preserve corneal sensitivity and tear volume. Furthermore, formation of corneal epithelial erosion was suppressed in DED model mice treated with the inhibitor. These results suggest that topical application of the selective Sema3A inhibitor may be effective for treatment of DED.

Academic Significance and Societal Importance of the Research Achievements

ドライアイは有病率が高い疾患であるが、神経再生または保護の観点からの治療法はなく、現行の涙液構成成分の補充療法だけでは治療が不十分な例も多い。神経再生を促進するビナキサントンを新たなドライアイ治療薬として開発できれば、より多くのドライアイ患者の症状を軽減できると考えられ、本研究でその可能性を示すことができた。ビナキサントンを用いることで、レーザー屈折矯正手術(レーシック)や全層角膜移植術の後に生じることのある知覚低下や涙液分泌低下の症状を緩和できる可能性もある。

Report

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

    (2 results)

All 2017

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (1 results)

  • [Journal Article] The Semaphorin 3A inhibitor SM-345431 preserves corneal nerve and epithelial integrity in a murine dry eye model2017

    • Author(s)
      Yamazaki Risa、Yamazoe Katsuya、Yoshida Satoru、Hatou Shin、Inagaki Emi、Okano Hideyuki、Tsubota Kazuo、Shimmura Shigeto
    • Journal Title

      Scientific Reports

      Volume: 7 Issue: 1

    • DOI

      10.1038/s41598-017-15682-1

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] セマフォリン3A阻害薬ビナキサントンによる新規ドライアイ治療の可能性2017

    • Author(s)
      山崎 梨沙、山添 克弥、吉田  悟、羽藤  晋、稲垣 絵海、岡野 栄之、坪田 一男、榛村 重人
    • Organizer
      角膜カンファランス2018
    • Related Report
      2017 Research-status Report

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

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