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Gene Therapy for Retinal Degeneration using Home-grown Gene Transfer Vectors-Aim for Clinical Trial-

Research Project

Project/Area Number 15209057
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Ophthalmology
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

ISHIBASHI Tatsuro  Kyushu University, Department of Ophthalmology, Professor, 大学院医学研究院, 教授 (30150428)

Co-Investigator(Kenkyū-buntansha) SUEISHI Katuso  Kyushu University, Department of Pathology, Professor, 大学院医学研究院, 教授 (70108710)
YONEMITSU Yoshikazu  Kyushu University, Graduate School of Medical Sciences, Professor, 大学院医学研究院, 特任教授 (40315065)
SONODA Ko-Hei  Kyushu University, Department of Ophthalmology, Research Associate, 大学院医学研究院, 助手 (10294943)
GOTO Yoshinobu  International University of Health and Welfare, Faculty of Rehabilitation, Associate Professor, リハビリテーション学部, 助教授 (30336028)
IKEDA Yasuhiro  Kyushu University, University Hospital, Research Associate, 大学病院, 助手 (20380389)
Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥46,540,000 (Direct Cost: ¥35,800,000、Indirect Cost: ¥10,740,000)
Fiscal Year 2005: ¥10,920,000 (Direct Cost: ¥8,400,000、Indirect Cost: ¥2,520,000)
Fiscal Year 2004: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2003: ¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000)
KeywordsGene therapy / Retinal degeneration / Neural progenitor cells / SIV vector / PEDF / FGF-2 / Age-related macular degeneration / hFGF-2 / RCSラット / rdsマウス / PEDF
Research Abstract

1. The assessment of the efficacy of gene therapy for the animal models of retinal degeneration
1) Development of new gene therapy technology
We developed the new SIV (simian immunodeficiency virus) vectors carrying hFGF-2 or both hPEDF and hFGF-2 (SIV-FGF-2 or SIV-dual). Moreover, we developed the system for large-scale production of SIV-hPEDF with the aim of the clinical trail.
2) We showed the synergistic therapeutic effect using SIV-hPEDF and SIV-hFGF-2 for two animal models of retinal degeneration (RCS rats and rds mice)
2. The establishment of new gene therapy strategy by use of neural progenitor cells
1) Development of the culture method to isolate neural progenitor cells from ciliary body of the eye
We identified a new and divergent mechanism (a reprogramming system) underlying the neural differentiation of ciliary body-derived cells via sphere formation. The nestin-negative epithelial-like cells from ciliary body came to express nestin.
2) We demonstrated the efficient gene transfer to neural progenitor cells from ciliary body of the eye via SIV vector
3. Remains
1) We evaluated the ability of our 3rd generation SIV vectors to transfer genes into nonhuman primate retinas.
2) We suggested the possibility that VEGF-C and VEGF-D expression in RPE modify the ocular angiogenesis, such as age-related macular degeneration (AMD) as angiogenic stimulators.

Report

(4 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (19 results)

All 2007 2006 2005 2004 Other

All Journal Article (19 results)

  • [Journal Article] Interleukin-18 regulates pathological intraocular neovascularization2007

    • Author(s)
      Qiao H, Ishibashi T, et al.
    • Journal Title

      J Leukoc Biol (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Sphere formation of ocular epithelial cells in the ciliary body is a reprogramming system for neural differentiation.2006

    • Author(s)
      Kohno R
    • Journal Title

      Brain Res. 1093・1

      Pages: 54-70

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The regulation of vascular endothelial growth factors (VEGF-A,-C,and -D) expression in the retinal pigment epithelium.2006

    • Author(s)
      Ikeda Y
    • Journal Title

      Exp Eye Res 83・5

      Pages: 1031-1040

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] nterleukin-18 regulates pathological intraocular neovascularization.2006

    • Author(s)
      Qiao H
    • Journal Title

      J Leukoc Biol. 115・11(in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Sphere formation of ocular epithelial cells in the ciliary body is a reprogramming system for neural differentiation.2006

    • Author(s)
      Kohno R, Ishibashi T, et al.
    • Journal Title

      Brain Res 1093(1)

      Pages: 54-70

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The regulation of vascular endothelial growth factors (VEGF-A,-C, and-D) expression in the retinal pigment epithelium.2006

    • Author(s)
      Ikeda Y, Ishibashi T, et al.
    • Journal Title

      Exp Eye Res 83(5)

      Pages: 1031-1040

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Infiltration of COX-2-expressing macrophages is a prerequisite for IL-1 beta-induced neovascularization and tumor growth.2005

    • Author(s)
      Nakao S
    • Journal Title

      J Clin Invest. 115・11

      Pages: 2979-2991

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The 5-Year incidence and Risk Factors for Age-Related Maculopathy in a General Japanese Population : The Hisayama Study.2005

    • Author(s)
      Miyazaki M
    • Journal Title

      Invest Ophthalmol Vis Sci 46・6

      Pages: 1907-1910

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 総説 : 遺伝子治療の臨床応用2005

    • Author(s)
      池田 康博
    • Journal Title

      眼科 47・10

      Pages: 1323-1333

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Infiltration of COX-2-expressing macrophages is a prerequisite for IL-1 beta-induced neovascularization and tumor growth.2005

    • Author(s)
      Nakao S, Ishibashi T, et al.
    • Journal Title

      J Clin Invest 115(11)

      Pages: 2979-2991

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] The 5-year incidence and risk factors for age-related maculopathy in a general Japanese population : the Hisayama study.2005

    • Author(s)
      Miyazaki M, Ishibashi T, et al.
    • Journal Title

      Invest Ophthalmol Vis Sci 46(6)

      Pages: 1907-1910

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Infiltration of COX-2-expressing macrophages is a prerequisite for IL-beta-induced neovascularization and tumor growth.2005

    • Author(s)
      Nakao S
    • Journal Title

      J Clin Invest. 115

      Pages: 2979-2991

    • Related Report
      2005 Annual Research Report
  • [Journal Article] A New Method for Comprehensive Bird's eye Analysis of the Surgically Excised Internal Limiting Membrane.2005

    • Author(s)
      Hisatosmi T
    • Journal Title

      Am J Ophthalmol 139

      Pages: 1121-1122

    • Related Report
      2005 Annual Research Report
  • [Journal Article] The 5-Year Incidence and Risk Factors for Age-Related Maculopathy in a General Japanese Population: The Hisayama Study.2005

    • Author(s)
      Miyazaki M
    • Journal Title

      Invest Ophthalmol Vis Sci 46

      Pages: 1907-1910

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Cytoplasmic Expression and Extracecellular Deposition of an Antiangiogenic Factor, Pigment Epithelium-Derived Factor, in Human Atherosclerotic Plaques.2005

    • Author(s)
      Baba H
    • Journal Title

      Arterioscler Thromb Vasc Biol. 25

      Pages: 1938-1944

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 遺伝子治療の臨床応用2005

    • Author(s)
      池田 康博
    • Journal Title

      眼科 47

      Pages: 1323-1333

    • NAID

      40006985339

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 網膜の遺伝子治療2005

    • Author(s)
      向野利一郎
    • Journal Title

      日本臨床 63

      Pages: 679-687

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 各種疾患の診断と治療:網膜色素変性の遺伝子治療2004

    • Author(s)
      池田康博
    • Journal Title

      眼科診療Q&A 34

      Pages: 12-14

    • Related Report
      2004 Annual Research Report
  • [Journal Article] 遺伝子治療の可能性

    • Author(s)
      池田康博
    • Journal Title

      あたらしい眼科・別冊「緑内障・新しい診方・考え方」 (in press)

    • Related Report
      2004 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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