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Development of new treatment modality for daibetic macular edema using animal models

Research Project

Project/Area Number 23390400
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Ophthalmology
Research InstitutionShinshu University

Principal Investigator

MURATA Toshinori  信州大学, 学術研究院医学系, 教授 (50253406)

Co-Investigator(Kenkyū-buntansha) ISHIBASHI Tatsuro  九州大学, 大学院医学研究院, 教授 (30150428)
Project Period (FY) 2011-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000)
Fiscal Year 2014: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2013: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2012: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2011: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Keywords黄斑浮腫 / 糖尿病 / 血管透過性亢進 / adrenomedullin / kockout mouse / VEGF / 糖尿病黄斑浮腫 / 糖尿病網膜症 / 遺伝子改変マウス / ノックアウトマウス / トランスジェニックマウス / kimbaマウス / アドレノメデュリン / RAMP-2 / 光干渉断層計 / 蛍光眼底造影 / RAMP2 / タイトジャンクション / 基底膜
Outline of Final Research Achievements

Using two mouse model of retinal edema, i.e., receptor-activity-modifying protein (RAMP)-2 knockout mouse and kimba mouse which overexpresses vascular endothleial growth factor (VEGF) in the retina, we pursued the possibility for experimental treatment for macular edema. We investigated the effect of intraocular injection ofβ-catenin、PPARγ-ligand、apelin on retinal vascular leakage, but none of them exhibited prominent reducing effect of fluorescein dye leakage in flurorescein angiography. Then we investigated the effect of intravitreal and systemic injection of adrenomedullin on the hyperpermeability of retinal vessels in kimba mice. Adrenomedullin reduced fluorescein dye leakage from retinal vessels in kimba mice suggesting its therapeutic effect on retinal edema, in which VEGF plays a causative role. Since half-life of adrenomedullin is short, we consider that we have to synthesize a fusion protein of adrenomedullin and Fc portion of IgG to make its effect long lasting.

Report

(5 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (12 results)

All 2015 2014 2013 2012 2011

All Journal Article (10 results) (of which Peer Reviewed: 9 results,  Acknowledgement Compliant: 4 results) Presentation (2 results)

  • [Journal Article] Physiological significance of recombination-activating gene 1 in neuronal death, especially optic neuropathy.2015

    • Author(s)
      Hirano T, Murata T, Hayashi T.
    • Journal Title

      FEBS J

      Volume: 282 Issue: 1 Pages: 129-141

    • DOI

      10.1111/febs.13109

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Effect of Laser wavelength on delivering appropriate laser burns through the opaque lens using a pattern scan laser.2014

    • Author(s)
      Hirano T, Iesato Y, Imai A, Toriyama Y, Kikushima W, Murata T.
    • Journal Title

      Ophthalmic Res

      Volume: 51 Issue: 4 Pages: 204-209

    • DOI

      10.1159/000357918

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Detection of fovea-threatening diabetic macular edema by optical coherence tomography to maintain good vision by prophylactic treatment2014

    • Author(s)
      Hirano T, Iesato Y, Toriyama Y, Imai A, Murata T.
    • Journal Title

      Ophthalmic Res

      Volume: 52 Issue: 2 Pages: 65-73

    • DOI

      10.1159/000362372

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Correlation between diabetic retinopathy severity and elevated skin autofluorescence as a marker of advanced glycation end-product accumulation in type 2 diabetic patients2014

    • Author(s)
      Hirano T, Iesato Y, Toriyama Y, Imai A, Chiba D, Murata T.
    • Journal Title

      J Diabetes Complications

      Volume: 28 Issue: 5 Pages: 729-734

    • DOI

      10.1016/j.jdiacomp.2014.03.003

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Effect of Laser Wavelength on Delivering Appropriate Laser Burns through the Opaque Lens Using a Pattern Scan Laser.2014

    • Author(s)
      Hirano T, Iesato Y, Imai A, Toriyama Y, Kikushima W, Murata T.
    • Journal Title

      Ophthalmic research

      Volume: 51

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Correlation between diabetic retinopathy severity and elevated skin autofluorescence as a marker of advanced glycation end-product accumulation in type 2 diabetic patients2014

    • Author(s)
      Takao Hirano, Yasuhiro Iesato, Yuichi Toriyama, Akira Imai, Dai Chiba, Toshinori Murata
    • Journal Title

      Journal of Diabetes and Its Complications

      Volume: 28

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Adrenomedullin-RAMP2 system is crucially involved in retinal angiogenesis2013

    • Author(s)
      Iesato Y, Tanaka M, et al.
    • Journal Title

      Am J Pathol.

      Volume: 182 Issue: 6 Pages: 2380-90

    • DOI

      10.1016/j.ajpath.2013.02.015

    • Related Report
      2013 Annual Research Report 2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Age-Related Decrease of the Retinal Vasculature Area Identified with a Novel Computer-Aided Analysis System2012

    • Author(s)
      Yamamoto Y, Yamamoto Y, Marugame A, Ogura M, Saito A, Ohta K, Fukumoto M, Murata T
    • Journal Title

      The Tohoku Journal of Experimental Medicine

      Volume: 228 Issue: 3 Pages: 229-237

    • DOI

      10.1620/tjem.228.229

    • NAID

      10031127352

    • ISSN
      0040-8727, 1349-3329
    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of spontaneous neuropathy in NF-κBp50-deficient mice by calcineurin-signal involving impaired NF-κB activation2011

    • Author(s)
      Nakamura-Yanagidaira T
    • Journal Title

      Mol Vis

      Volume: 17 Pages: 2157-2170

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pathogenesis and pathology of retinal hemorrhage, soft exudates, hard exudates and retinal ischemia2011

    • Author(s)
      中尾新太郎
    • Journal Title

      眼科

      Volume: 53 Pages: 1063-1070

    • Related Report
      2011 Annual Research Report
  • [Presentation] Diabetic macular edema treatment in Japan2011

    • Author(s)
      Murata T
    • Organizer
      The Second Liaoning International Ophthalmology-New Technique Conference
    • Place of Presentation
      Shenyang, China(招待講演)
    • Year and Date
      2011-09-24
    • Related Report
      2011 Annual Research Report
  • [Presentation] The incomplete formation of tight junction in RPE of adrenomedulin KO mice2011

    • Author(s)
      Murata T
    • Organizer
      The fourth global Chinese Ophthalmic Conference
    • Place of Presentation
      Guangzhou, Chinas(招待講演)
    • Year and Date
      2011-09-08
    • Related Report
      2011 Annual Research Report

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Published: 2011-04-06   Modified: 2019-07-29  

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