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Experimental Study on Changes of Intraocular Pressure by the Application of Griseolic Acid

Research Project

Project/Area Number 63570832
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Ophthalmology
Research InstitutionHIROSHIMA UNIVERSITY

Principal Investigator

MISHIMA Hiromu  Hiroshima Univ. School of Med. Associate Professor, 医学部, 助教授 (20034100)

Co-Investigator(Kenkyū-buntansha) SHIMADA Sigeaki  Hiroshima Univ. School of Med. Assistant Prof., 医学部附属病院, 助手 (30196480)
NAKANO Kensuke  Hiroshima Univ. School of Med. Assistant Prof., 医学部附属病院, 助手 (30164247)
Project Period (FY) 1988 – 1989
Project Status Completed (Fiscal Year 1989)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1989: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1988: ¥1,500,000 (Direct Cost: ¥1,500,000)
Keywordsgriseolic acid / cAMP-phosphodiesterase inhibitor / intraocular pressure / cyclic AMP / Morphological change / aqueous humor dynamics / ocular penetration / melanin / cAMP分解酵素阻害剤 / 房水循環動態 / CAMP-poshodi esterase阻害剤 / 眼圧下降 / griseolic acid / 緑内障
Research Abstract

1. REDUCTION IN INTRAOCULAR PRESSURE Topical application of 0.5% griseolic acid-ester (GA-ester) showed no significant ocular hypotensive response. But, a significant reduction in intraocular pressure (IOP) was observed at 2hr after topical application of 1% GA-ester. The ocular hypotensive response lasted 5 hrs after topical application of 2% GA-ester. IOP in rabbits was reduced in a dose-related manner following topical application of concentration of 0.5% to 2%.
2. cAMP ACCUMULATION IN IRIS-CILIARY BODY GA-ester at 100muM markedly increased the cAMP levels in rabbit iris-ciliary bodies. cAMP levels in GA-ester treated iris-ciliary body is four times higher than in IBMX treated one.
3. MORPHOLOGICAL CHANGES IN IRIS-CILIARY BODY Topical application of 2% GA-ester (50ul) caused nb morphological changes in ciliary process at 1 to 24h. No bemorrhage, no stromal edema nor invasion of inflammatory cells were observed. Even electron micrograph could not detect any morphological changes in the ciliary epithelium after instillation of 2% GA-ester.
4. CHANGES IN AQUEOUS HUMOR DYNAMICS The mean aqueous flow rate measured by fluorophotometry was significantly lower in GA- treated eyes than in control eyes. Topical application of Ga- ester did not alter tonographic outflow or uveoscleral outflow measured using fluorescein isothiocyanate labeled-dextran.
5. INTRAOCULAR PENETRATION OF GRISEOLIC ACID-ESTER 1 hour after topical application, 12.5%, 0.065%, O.010%, 0.017% and 0.010% of topically applied GA-ester was detected, respectively, in the conjunctive, cornes, aqueous humor, iris and ciliary body.
6. AFFINITY OF GRISEOLIC ACID -ESTER FOR SYNTHETIC MELANIN Timolol exhibited binding affinity to synthetic melanin. But, GA- ester did not bind to synthetic melanin.

Report

(3 results)
  • 1989 Annual Research Report   Final Research Report Summary
  • 1988 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Hiromu Mishima: "Griseolic acid,ACAMP phosphodiesterase inhibitor,and its ester increase in celluar CAMP levels and reduction of intraocular pressure." Advances in Second Messenger and Phosphoprotein Research.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Hiromu Mishima: "A cyclic AMP phosphodiesterase inhibitor a derivatives of griseolic acid,lowerss rabbit intraocular pressure" Current Eye Research.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Hiromu Mishima: "Effect of griseolic acid,CAMP-phosphodiesterase inhibitor on aqueous humor dynamics in rabbits" Current Eye Research.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 三嶋弘: "グリセオ-ル酸エステルとメラニン色素" 新しい眼科.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 三嶋弘: "β作動薬、メラニン色素とグリセオ-ル酸の眼圧下降作用" 日本眼科学会雑誌.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 三嶋弘: "緑内障薬物治療の新しい方向" 新しい眼科.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 三嶋弘: "眼科Mook40緑内障の診療ガイド" 金原出版, 236 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Mishima, H.: "Griseolic acid, A cAMP phosphodiesterase inhibitor, and its ester-Increase in cellular CAMP levels and reduction of intraocular pressure." Advances in Second Messenger and Phosphoprotein Research. (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Mishima, H.: "A cyclic AMP phosphodiesterase inhibitor, a derivatives of griseolic acid, lowers Rabbit intraocular pressure." Curr. Eye Res.:1990.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Mishima, H.: "Effect of a cyclic AMP phosphodiesterase inhibitor, 8' -pivaloyloxymethylester (POM-ester) of griseolic acid, on aqueous humor dynamics in rabbits." Curr.Eye Res.:1990.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Mishima, H.: "Ocular hypotensive effect of griseolic acid and melanin." J.Eye:1990.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Mishima, H.: "Changes in ocular hypotensive effect of griseolic acid with isoproterenol, timolol and melanin. Acta Soc. Ophthalmol." Jpn.:1990.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Mishima, H.: "Ocular pharmachology of anti-glaucomatous drugs: New drugs effecting on intracellular mediator." J.Eye :1990.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Mishima, H.: A guide book for glaucoma. Kanahara Company, 236 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Hiromu Mishima: "Effect griseolic acid cAMP-phosphodiesterase inhibitory on aqueous humor dynamics in rabbits" Current Eye Research.

    • Related Report
      1989 Annual Research Report
  • [Publications] 三嶋弘: "グリセオ-ル酸とメラニン色素" あたらしい眼科.

    • Related Report
      1989 Annual Research Report
  • [Publications] 三嶋弘: "β作動薬、メラニン色素とグリセオ-ル酸の眼圧下降作用" 日眼雑誌.

    • Related Report
      1989 Annual Research Report
  • [Publications] 三嶋弘: "緑内障薬物治療の新しい方向" あたらしい眼科.

    • Related Report
      1989 Annual Research Report
  • [Publications] 三嶋弘: "眼科Mook40 緑内障の診療ガイド" 236 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Mishma,H.K;kiuchi,Y.,et al: Current Eye Res.

    • Related Report
      1988 Annual Research Report
  • [Publications] Mishima, H.;KinCHI, Y., et al: Investigafive Ophthalmology. 29. 84 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 三嶋弘・木内良明: "眼科mook 緑内障の新薬(細胞の情報伝達機構に作用する薬物について)" 金原出版,

    • Related Report
      1988 Annual Research Report

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Published: 1988-04-01   Modified: 2016-04-21  

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