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RESEARCH ON PATHOGENESIS AND TREATMENT OF OCULAR VASCULAR DISEASES

Research Project

Project/Area Number 09307040
Research Category

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

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

Principal Investigator

INOMATA Hajime  Graduate School of Medical Sciences KYUSHU UNIVERSITY Professor, 大学院・医学研究院, 教授 (30038674)

Co-Investigator(Kenkyū-buntansha) SAKAMOTO Taiji  Faculty of Medicine KYUSHU UNIVERSITY Assistant, 医学部・附属病院, 助手 (10235179)
ISHIBASHI Tatsuro  Graduate School Medical Sciences KYUSHU UNIVERSITY Associate Professor, 大学院・医学研究院, 助教授 (30150428)
Project Period (FY) 1997 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥34,800,000 (Direct Cost: ¥34,800,000)
Fiscal Year 2000: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1999: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1998: ¥5,500,000 (Direct Cost: ¥5,500,000)
Fiscal Year 1997: ¥22,000,000 (Direct Cost: ¥22,000,000)
KeywordsNeovascularization / Malignant Melanoma / Adenovirus Vector / Subretinal Neovascularization / Wound Healing / Tissue Plasminogen Activator / Transforming Growth Factor-β / Vascular Endothelial Growth Factor / トランスフォーミング増殖因子TGF-b / 糖尿病網膜症 / 遺伝子治療 / 組織因子 / 電気パルス / ウイルスベクター / TGF-β / アドレノメジュリン / 眼内血管新生 / 角膜血管新生 / MCP-I / VEGF / アデノウィルスベクター / 低酸素 / 転写因子 / 網膜血管内皮細胞 / 遺伝子導入 / IL-8 / ras inhibior
Research Abstract

We examined the effect of adenovirus-mediated gene transfer of a soluble receptor of vascular endothelial growth factor (VEGF) on the growth of experimental eyelid malignant melanoma, and it was found that the VEGF receptor (flt-1) gene inhibited the growth of the tumor. However, it caused the severe skin ulcer. Similarly, experimental subretinal neovascularization was inhibited by adenovirus-mediated soluble VEGF/flt-1 receptor gene transfection : as a role of VEGF and possible treatment for SRN in age-related macular degeneration. However, severe damages occurred in the sensory retina.
From these experimental studies, it became clear that neovascularization is rather important and indispensable phenomenon for wound healing of the tissues and organs. Therefore, it seems to be more important to inhibit the inflammation and/or tissue fibrosis during the wound healing.
To have the ideal wound healing, we prepared adenovirus vector to inhibit tissue plasminogen activator and transforming growth factor-β (TGF-β). Our results demonstrated that TGF-β indeed plays a critical role in the process of corneal opacification, edema and angiogenesis, and that adenovirus-mediated expression of a soluble TGF-β receptor can be therapeutically useful.

Report

(5 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (60 results)

All Other

All Publications (60 results)

  • [Publications] Sakamoto T, et al: "Target gene transfer of tissue plasminogen activator to cornea by electric pulse inhibits intracameral fibrin formation and corneal cloudiness."Human Gene Therapy. 10・10. 2551-2557 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Zhang X, et al: "Electron microscopic study on the development of precapsular layer in eyes with exfoliation syndrome."Jpn J Ophthalmol. 44・1. 9-14 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shiose S, et al: "Gene transfer of a soluble receptor of VEGF inhibits the growth of experimental eyelid malignant melanoma."Invest Ophthalmol Vis Sci. 41・9. 2395-2403 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Honda M, et al: "Experimental subretinal neovascularization is inhibited by adenovirus-mediated soluble VEGF/flt-1 receptor gene transfection."Gene Therapy. 7・11. 978-985 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sakamoto T, et al: "Blockage of TGF-β by in vivo gene transfer of a soluble TGF-b type II receptor in the muscle inhibits corneal opacification, edema and angiogenesis."Gene Therapy. 7・22. 1914-1924 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Inomata H, et al: "Depigmented atrophic lesions in sunset glow fundi in Vogt-Koyanagi-Harada disease."Am J Ophthalmol. 130・4(印刷中). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 猪俣孟 ほか: "眼の細胞生物学"(株)中山幸書店. 323 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 猪俣孟: "眼の組織・病理アトラス"(株)医学書院. 367 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sakamoto T, et al: "Target gene transfer of tissue plasminogen activator to cornea by electric pulse inhibits intracameral fibrin formation and corneal cloudiness."Human Gene Therapy. 10-10. 2551-2557 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Zhang X, et al: "Electron microscopic study on the development of precapsular layer in eyes with exfoliation syndrome."Jpn J Ophthalmol. 44-1. 9-14 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shiose S, et al: "Gene transfer of a soluble receptor of VEGF inhibits the growth of experimental eyelid malignant melanoma."Invest Ophthalmol Vis Sci. 41 9. 2395-2403 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Honda M, et al: "Experimental subretinal neovascularization is inhibited by adenovirus-mediated soluble VEGF/flt-1 receptor gene transfection"Gene Therapy. 7-11. 978-985 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sakamoto T, et al: "Blockage of TGF-βby in vivo gene transfer of a soluble TGF-b type II receptor in the muscle inhibits corneal opacification, edema and angiogenesis."Gene Therapy. 7-22. 1914-1924 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Inomata H, et al: "Depigmented atrophic lesions in sunset glow fundi in Vogt-Koyanagi-Harada disease."Am J Ophthalmol. 130-4 (in press). (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Inomata H, et al: "Ocular Cell Biology"Nakayama-Shoten Co.Ltd. (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Inomata H: "Atlas of Ocular Histology and Pathology"Igaku-Shoin Co.Ltd. (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sakamoto T, et al: "Target gene transfer of tissue plasminogen activator to cornea by electric pulse inhibits intracameral fibrin formation and corneal cloudiness."Human Gene Therapy. 10・10. 2551-2557 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Zhang X, et al: "Electron microscopic study on the development of precapsular layer in eyes with exfoliation syndrome."Jpn J Ophthalmol. 44・1. 9-14 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shiose S, et al: "Gene transfer of a soluble receptor of VEGF inhibits the growth of experimental eyelid malignant melanoma."Invest Ophthalmol Vis Sci. 41・9. 2395-2403 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Honda M, et al: "Experimental subretinal neovascularization is inhibited by adenovirusmediated soluble VEGF/flt-1 receptor gene transfection."Gene Therapy. 7・11. 978-985 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Sakamoto T, et al: "Blockage of TGF-β by in vivo gene transfer of a soluble TGF-β type II receptor in the muscle inhibits corneal opacification, edema and angiogenesis."Gene Therapy. 7・22. 1914-1924 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Inomata H, et al: "Depigmented atrophic lesions in sunset glow fundi in Vogt-Koyanagi-Harada disease."Am J Ophthalmol. 130・4(印刷中). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 猪俣孟 ほか: "眼の細胞生物学"(株)中山幸書店. 323 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 猪俣孟: "眼の組織・病理アトラス"(株)医学書院. 367 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Oshima Y, et al: "The comparative benefits of glaucoma filtering surgery with an electric-pulse targeted drug delivery system demonstrated in Ananimal model,"Ophthalogy. 106・6. 1140-1146 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ishibashi T, et al: "Peripheral choroidal neovescularization in proliferative diabetic retinopath:Histopatho-logic and ultrastructural study,"Ophthalogy. 213・3. 154-158 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ito S, et al: "The effect of tranilast on exrimental proliferative vitreoretinopathy."Grafe's Arch Clin Exp Ophthalmol. 237・8. 691-696 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Sakamoto T, et al: "Target gene transter of tissue plaminogen activator to comea by electric pulse inhibits intracameral fibrin fomation and comeal coludiness,"Human Gene Therapy. 10・10. 2551-2557 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 石橋達朗,ほか: "眼内血管病変の細胞生物学"日眼会誌. 103・12. 923-947 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yoshida A, et al: "Suppression of retinal neobascularization by the NF-KB inhibitor pyrrolidine dithiocarbonate in mice,"Invest Ophthalmol Vis Sci. 40・7. 1624-1629 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 猪俣 孟(分担): "ぶどう膜炎の病理"医学書院. 407 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 猪俣 孟 編(分担): "眼科の最先端"先端医療技術研究所. 276 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kubota T: "Double staining of proteoglycans and the HNK-I carbohydrate epitope in pseudoexfoliation material." Current Eye Research. 17・1. 60-64 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kubota T: "Distribution of proteoglycans in the trabecular tissue of eyes with neovascular glaucoma." German J Ophthalmol. 5・6. 392-398 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Minagawa H: "Supression of infections virus spread and corneal opacification by the combined use of recombinant interferon beta and interleukin-10 following corneal infection with herpes simplex virus-1 in mice." Antiviral Research. 36・2. 99-105 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Sakamoto T: "Retinal functional change caused by adenoviral vector-mediated transfection of LacZ gene." Human Gene Thrapy. 9・4. 789-799 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yoshida A: "The role of NF-kB in retinal neovascularization in the rat:Possible involvement of cytokine-induced neutrophil chemoattractant (CINC),a member of the interleukin-8 family." J Histochem Cytochem. 46・4. 429-436 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yoshida A: "Role of NF-kB-mediated interleukin-8 expression in intraocular neovascularization." Invest Ophthalmol Vis Sci. 39・7. 1097-1106 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Sakamoto T: "A vitrectomy improves the transfection efficiency of adenoviral vector-mediated gene transfer to Muller cells." Gene Therapy. 5・8. 1088-1097 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Oshima Y: "Targeted gene transfer to corneal endothelium in vivo by electric puls." Gene Therapy. 5・10. 1347-1354 (1996)

    • Related Report
      1998 Annual Research Report
  • [Publications] Goto M: "Two cases of unilateral retinal neovascularization in Turner syndrome." Am J Ophthalmol. 126・7. 144-146 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Sonoda K: Invest Ophthalmol Vis Sci. 39・12. 2245-2251 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Inomata H(分担): "Ophthalmology,Vogt-Koyanagi-Harada syndrome" Mosby International Ltd, 1500(4) (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Oshima Y: "Effect of electric pulses and antiproliferative drugs on cultured bovine retinal pigment epithelial cells." Current Eye Research. 16・1. 64-70 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 猪俣 孟: "黄斑部の名称" 日本眼科学会雑誌. 101・3. 201-208 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ishibashi T: "Expression of vascular endothelial growth factor in experimental choroidal neovascularization." Graefe's Arch Clin Exp Ophthalmol. 235・3. 159-167 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 坂本 泰二: "眼科領域のIn Vitro血管新生" 日本眼科紀要. 48・4. 435-442 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kumano Y: "Hyperimmunoglobulinemia D in idiopathic retinal vasculitis." Graefe's Arch Clin Exp Ophthalmol. 235・6. 372-378 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Murata T: "The relationship between accumulation of advanced glycation end products and expression of vascular endothelial growth factor in human diabetic retinas." Diabetologia. 40・7. 764-769 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 猪俣 孟: "眼内血管新生" 日本眼科学会雑誌. 101・12. 906-926 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Sakamoto T: "Electroporation and bleomycin in glaucoma-filtering surgery." Invest Ophthalmol Vis Sci. 38・13. 2864-2868 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 石橋 達朗: "合併症治療の最前線-光凝固療法-" Complication-糖尿病と血管-. 2・2. 223-232 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 楢崎 陽子: "若年者にみられた進行性網膜血管閉塞の1例" 日本眼科紀要. 48・3. 296-300 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yoshida S: "Involvement of interleukin-8,vascular endothelial growth factor,and basic fibroblsast growth factor in tumor necrosis factor alpha-dependent angiogenesis." Molecular and Cellular Biology. 17・7. 4015-4023 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 重藤 真理子: "Insulin-like growth factor-I投与後に増悪した糖尿病網膜症の1例" 臨床眼科. 51・6. 1251-1255 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Oshima Y: "Synergistic effect of electric pulses and bleomycin on cultured rabbit subconjunctival fibroblasts." Graefe's Arch Clin Exp Ophthalmol. 236・1. 52-60 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 石橋 達朗: "糖尿病網膜症-病理学-" 日本臨床. 55・増刊. 948-952 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Sakamoto T: "Current Opinions in the Kyoto Cornea Club" Kinoshita S,Ohashi Y, 108 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 猪俣 孟: "糖尿病眼科の臨床" 福田 雅俊,松井 瑞夫,猪俣 孟, 188 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 石橋 達朗: "眼科New Insight(10)眼とバリアー" 木下 茂,石橋 達朗, 191 (1997)

    • Related Report
      1997 Annual Research Report

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

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