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脈絡膜血管新生における炎症細胞集積メカニズムについての分子生物学的研究

Research Project

Project/Area Number 14770944
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Ophthalmology
Research InstitutionTokyo Medical and Dental University

Principal Investigator

二神 創  東京医科歯科大学, 医学部附属病院, 助手 (70301158)

Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2002: ¥2,100,000 (Direct Cost: ¥2,100,000)
Keywords網膜色素上皮細胞 / MCP-1 / 脈絡膜新生血管 / 炎症細胞 / NF-κB / 酸化ストレス / 分化 / 脈絡膜血管新生 / 加齢黄斑変性
Research Abstract

加齢黄斑変性や強度近視にみられる脈絡膜血管新生は,成人の失明原因として重要な問題である。これらの疾患における新生血管膜の病理組織学的検では,マクロファージなどの炎症細胞浸潤が一つり特徴であり,このような炎症細胞の浸潤が種々のサイトカイン分泌を引き起こし,病像の増悪を招くと考えられるが,炎症細胞集積機構は不明であった。我々は網膜色素上皮細胞(RPE)の形質転換による遺伝子発現の変化が炎症細胞集積に重要ではないかと考えた。本研究では強力なマクロファージ遊走因子であるmonocyte chemoattractant protein-1)に注目し,RPEの形質転換に伴うMCP-1の発現変化を調べた。その結果,脱分化したRPEでは分化RPEに比べ著明なMCP-1の発現上昇がreal-time PCR, ELISA法ともに認められた。さらに脱分化RPEでは転写因子NF-κBの活性化がみられ,NF-κBの活性化を阻害するプロテアソーム・インヒビターの添加によりMCP-1の発現上昇が抑制されたことからRPEの脱分化に伴うMCP-1の発現上昇はNF-κBの活性化を介したものであることが分かった。さらに抗酸化剤を添加するとNF-κBの活性化に引き続くMCP-1の発現上昇も抑制され,脱分化RPEにおいてNF-κB活性化を生じる病的刺激は酸化ストレスではないかと考えられた。

Report

(2 results)
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • Research Products

    (9 results)

All Other

All Publications (9 results)

  • [Publications] Yoshida T, Futagami S, et al.: "Myopic choroidal neovascularization. A 10-year follow-up."Ophthalmology. 110. 1297-1305 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yasuzumi K, Futagami S, et al.: "Peripapillary crescent enlargement in highly myopic eyes evaluated by fluorescein and indocyanine green angiography"Br J Ophthalmol. 87. 1088-1090 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ohno-Matsui K, Futagami S, et al.: "Patchy atrophy and lacquer cracks predispose to the development of choroidal neovascularization in pathologic myopia."Br J Ophthalmol. 87. 570-573 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Baba T, Futagami S, et al.: "Prevalence and Characteristics of Foveal Retinal Detachment without Macular Hole in High Myopia."Am J Ophthalmol. 135. 338-342 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shimada N, Futagami S, et al.: "Retinal blood flow is reduced in high myopia."Graefes Arch Clin Exp Ophthalmol. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Kojima A, Futagami S, et al.: "factors associated with the development of chorioretinal atrophy around choroidal neovascularization in pathologic myopia."Graefes Arch Clin Exp Ophthalmol. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] Ohno-Matsui K, et al.: "Patchy atroply and lacquer crachs predispose to the development of choroidal neovascularisation in pathological myopia"British Journal of Ophthalmology. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Baba T, et al.: "Prevalence and characteristics of foveal retinal detachment without macular hole in high myopia"American Journal of Ophthalmology. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Yoshida T, et al.: "Long-term visual prognosis of choroidal neovascularization in high myopia : A comparison between age groups"Ophthalmology. 109. 712-719 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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