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Molecular modulation and gene therapy in choroidal neovascularization.

Research Project

Project/Area Number 09470385
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field Ophthalmology
Research InstitutionKansai Medical University

Principal Investigator

UYAMA Masanobu  Kansai Medical University, Department of Ophthalmology, Professor and Chairman, 医学部, 教授 (30025580)

Co-Investigator(Kenkyū-buntansha) MATSUSHIMA Masashi  Kansai Medical University, Assistant Professor, 医学部, 講師 (00192336)
TAKAHASHI Kanji  Kansai Medical University, Assistant Professor, 医学部, 講師 (60216710)
OGATA Nahoko  Kansai Medical University, Assistant Professor, 医学部, 講師 (60204062)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥13,200,000 (Direct Cost: ¥13,200,000)
Fiscal Year 1998: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1997: ¥9,600,000 (Direct Cost: ¥9,600,000)
Keywordsage-related macular degeneration / choroidal neovascularization / retinal pigment epithelium / angiogenic factor / basic fibroblast growth factor / vascular endothelial growth factor / gene therapy / gene induction / 網膜虚血再潅流 / VEGF / b-FGF / インターフェロンβ / 細胞成長因子
Research Abstract

1. Molecular modulation in choroidal neovascularization
Choroidal neovascularization (CNV) was induced in monkey and rat eyes by intense laser photocoagulations of the retina in the posterior pole. In experimental CNV, expression of mRNA of b-fibroblast growth factor (FGF), vascular endothelial growth factor (VEGF), trans-forming growth factor (TGF)-β, and their receptors were revealed, using in situ hybridization and immunohistochemistry, markedly in the early stage in developing of CNV, and slightly in the late stage. These results suggest development and regression of CNV were modulated by these cytokines.
2. Effect of Interferron β on development of CNV
Local (subtenon) or systemic administration of Interferron (IFN)-β inhibited development of CNV.Involution of CNV were due to enclosure by proliferatin of the retinal pigment epithelium (RPE). IFN-β upregulated expression of angiogenic
factors such as bFGF and VEGF in CNV.
3. Possibility of gene therapy in CNV
A vector of combination of hemagglutinating Virus of Japan (HVJ) and liposome was enveloped with antisense-olignucleotide or antisense plasmid, then intoroduced to CNV or RPE in vivo. They were successfully transferred in the target cells.
These results show gene therapy with HVJ-liposome method will be achieved effectively in CNV treatment.

Report

(3 results)
  • 2000 Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] 緒方奈保子 他: "脈絡膜新生血管とサイトカインー遺伝子治療へ(眼研究の最先端)"Practical Ophthalmology. 58. 112-118 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Uyama M, et al: "Changes in choriocapillaris and retinal pigment epithelium in age-related macular degeneration"Molecular Vision. 5. 35-41 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Wada M, et al: "Expression of vascular endothelial growth factor and its receptor (KDR/flk-1) mRNA in experimental choroidal neovascularization"Curr Eye Res. 18. 203-213 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ogata N, et al: "Expression of transforming growth factor-β mRNA in experimental choroidal neovascularization"Curr Eye Res. 16. 9-18 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yi XJ et al: "Vascular endothelial growth factor expressin in choroidal neovascularization in rats"Graefe's Arch Clin Exp Ophthalmol. 235. 313-319 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ogata N, et al: "Phosphorothioate oligo-nucleotides induction into experimental choroidal neovascularization by HVJ-liposome system."Curr Eye Res. 18. 261-269 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Otsuji T, et al: "In vivo gene transfer into choroidal neovascularization by the HVJ liposome method"Graefe's Arch Exp Ophthalmol. 238. 191-199 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ogata N, et al: "Transfection of basic fibroblast growth factor (bFGF) gene of b FGF angisense gene into human retinal pigment epithelial cells"Graefe's Arch Clin Exp Ophthalmol. 237. 378-384 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 岩下憲四郎 他: "実験的脈絡膜新生血管において、インターフェロンβは網膜色素上皮の増殖を促進する(形態計測学的観察)"日本眼科学会雑誌. 103. 415-424 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 木本高志 他: "ラット眼の実験的脈絡膜新生血管に対するマウス・インターフェロンβの効果"日本眼科学会雑誌. 103. 363-370 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Uyama M, et al: "Changes in choriocapillaris and retinal pigment epithelium in age-related macular degeneration"Molecular Vision. 5. 35-41 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Wada M, et al: "Expression of vascular endothelial growth factor and its receptor (KDR/flk-1) mRNA in experimental choroidal neovascularization."Curr Eye Res. 18. 203-213 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ogata N, et al: "Expression of transforming growth factor-β mRNA in experimental choroidal neovascularization."Curr Eye Res. 16. 9-18 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yi XJ et al: "Vascular endothelial growth factor expression in choroidal neovascularization in rats."Graefe's Arch Clin Exp Ophthalmol. 235. 313-319 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ogata N, et al: "Phosphorothioate oligo-nucleotides induction into experimental choroidal neovascularization by HVJ-liposome system."Curr Eye Res. 18. 261-269 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Otsuji T, et al: "In vivo gene transfer into choroidal neovascularization by the HVJ liposome method."Graefe's Arch Clin Exp Ophthalmol. 238. 191-199 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ogata N et al: "Transfection of basic fibroblast growth factor (bFGF) gene of bFGF antisense gene into human retinal pigment epithelial cells."Graefe's Arch Clin Exp Opthalmol. 237. 678-684 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ogata N,et al: "Transfection of basic fibroblast growth factor(b-FGF)gene or b-FGF antisense gene into human retinal pigment epithelial cells." Graefe's Archive for Clinical and Experimental Ophthalmology. 237(in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ogata N,et al: "Phosphorothioate ologonucleotides induction into experimental choroidal neovascularization by HVJ-Liposome system." Current Eye Research. 18(in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ogata N,et al: "Expression of vascular endothelial growth factor and its receptor(KDR/Hk-1)mRNA in experimental choroidal neovascularization." Current Eye Research. 18(in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ogata N,et al: "Expression of vascular endothelial growth factor and its receptor,KDR,following retinal ischemia-reperfusion injury in the rat." Current Eye Research. 17. 1087-1096 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Miyashiro M,et al: "Midkine expression in transient retinal ischemia in the rat." Current Eye Research. 17. 9-13 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Miyashiro M,et al: "Expression of basic fibroblast growth factor and its receptor mRNA in retinal tissue following ischemic injury in the rat." Graefe's Archive for Clinical and Experimental Ophthalmology. 236. 295-300 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yamamoto C,et al: "Immunolocarization of transforming growth factor-β during wound repair in rat retina after laser photocaogulation." Graefe's Archive for Clinical and Experimental Ophthalmology. 236. 41-46 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yamamoto C, et al.: "Immunolocalizationof transforming growth factor-β during wound repair in the rat retina after laser photocoagulation." Graefe's Arch Clin Exp Ophthalmology. 236(in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Miyashiro M, et al.: "Basic fibroblast growth factor and its receptor expression in transient retinal ischemia in the rat." Graefe's Arch Clin Exp Ophthalmology. 236(in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 松島正史, 他: "実験的網膜静脈閉塞症における塩基性線維芽細胞増殖因子と塩基性線維芽細胞増殖因子レセプター1の発現" 日本眼科学会雑誌. 101. 564-570 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yi X, et al.: "Vascular endothelial growth factor expression in choroidal neovascularization in rats." Graefe's Arch Clin Exp Ophthalmology. 235. 313-319 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ogata N, et al.: "Expression of transforming growth factor-β mRNA in experimental choroidal neovascularization" Current Eye Research. 16. 9-18 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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