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Development of a new method for the treatment of herpetic keratitis using RNA interference

Research Project

Project/Area Number 18591923
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Ophthalmology
Research InstitutionThe University of Tokushima

Principal Investigator

SHIOTA Hiroshi  The University of Tokushima, Institute of Health Biosciences, Professor (20035736)

Co-Investigator(Kenkyū-buntansha) EGUCHI Hiroshi  The University of Tokushima, University Medical and Dental Hospital, Lecturer (30314868)
SHINOMIYA Kayo  The University of Tokushima, Institute of Health Biosciences, Lecturer (80322262)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,790,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,100,000 (Direct Cost: ¥2,100,000)
KeywordsRNA interference / herpes simplex virus / herpetic keratitis / DNA polymerase / aciclovir / carbocyclic oxetanocin G / trifluorothymidine / RNA干渉 / DNAポリメレース / チミジンキナーゼ
Research Abstract

Herpetic keratitis is a corneal disease due to the infection of herpes simplex virus (HSV) and regarded as one of the difficult ocular diseases to deal with because of its recurrence. Aciclovir ophthalmic ointment is the drug of choice for its treatment. This study is to develop waterly and safe drug for herpetic keratitis.
1) Aim to inhibit the appearance of DNA polymerase gene
Double strand RNA (dsRNA) was synthesized after careful investigation of the gene arrangement of DNA polymerase and selecting 21 base pairs which are specific to HSV. This is an siRNA based on 21 base pairs and inhibits the appearance of DNA polymerase gene thecretically. As experiments to investigate the preventive effect of the siRNA HSV was inoculated into rabbit corneas. One hour after the inoculation groups A and B were commenced to apply the siRNA eyedrop and the vehicle, respectively. Fourty-eight hours after the virus inoculaton lesions at inoculated sites were calculated by scoring system and the effect … More was judged by comparing the score between the groups. Regretably enough both groups showed dendritic ulcers and the siRNA eyedrop did not show the preventive effect. Next, as experiments to investigate the therapeutic effect of the siRNA treatment with the siRNA eyedrop (group C) and the vehicle (group D) were started 48 hours after HSV inoculation at which time dendritic ulcers were established. After the treatment for 5 days lesions in both groups were calculated by the scoring system and compared the score between the two groups. Regretably enough both groups exhibited geographic ulcers and the therapeutic effect of the siRNA eyedrop was not seen.
2) Therapeutic effect of carbccyclic oxetanocin G (C. OXT-G) eyedrop
Therapeutic effects of C. OXT-G eyedrop which is under investigaton by us and trifluorothymidine (TFT) eyedrop which is marketed in Europe and the U.S.A. were compared. HSV was inoculated into rabbit corneas and 48 hours later treatments with 0.1% C. OXT-G eyedrop, 1% TFT eyedrop and normal saline as control were started and continued for 4 days. As the result C. OXT-G and TFT eyedrop exhibited wonderful therapeutic effects and these effects were equal. C. OXT-G which is under investigation seems to be a new eyedrop for the treatment of herpetic keratitis in humans. Less

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (4 results)

All 2007

All Presentation (4 results)

  • [Presentation] 角膜潰瘍の診断と治療2007

    • Author(s)
      塩田 洋
    • Organizer
      第54回浜松医科大学眼科症例検討会
    • Place of Presentation
      浜松市
    • Year and Date
      2007-12-15
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Diagnosis and treatment of corneal ulcers.2007

    • Author(s)
      SHIOTA, Hiroshi
    • Organizer
      54th Case Investigational Meeting in Ophthalmology at Hamamatsu University School of Medicine
    • Place of Presentation
      Hamamatsu City
    • Year and Date
      2007-12-15
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 角膜ヘルペス治療薬の過去、現在、未来2007

    • Author(s)
      塩田 洋
    • Organizer
      第17回抗ウイルス療法研究会
    • Place of Presentation
      高松市
    • Year and Date
      2007-05-26
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Past, present and future drugs in the treatment of herpetic keratitis.2007

    • Author(s)
      SHIOTA, Hiroshi
    • Organizer
      17^<th> Meeting of Antiviral Therapy
    • Place of Presentation
      Takamatsu City
    • Year and Date
      2007-05-26
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2006-04-01   Modified: 2016-04-21  

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