Extracellular matrix as a new therapeutic target for choroidal neovascularization

• Project/Area Number: 21592237
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Nagoya City University
• Principal Investigator: NOZAKI Miho 名古屋市立大学, 大学院・医学研究科, 講師 (00295601)
• Co-Investigator(Kenkyū-buntansha): OGURA Yuichiro 名古屋市立大学, 大学院・医学研究科, 教授 (70191963) ; YASUKAWA Tsutomu 名古屋市立大学, 大学院・医学研究科, 准教授 (00324632)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 加齢黄斑変性 / 脈絡膜新生血管 / VEGF-A / オステオポンチン / マクロファージ / 細胞外マトリックス / VEGF

Research Abstract

Osteopontin(OPN) is a chemokine like phospholyrated glycoprotein and involved in inflammation, tumor genesis and wound healing. The purpose of the study was to clarify a role of OPN in the development of laser-induced choroidal neovascularization(CNV) in mice. OPN neutralizing Abs significantly abolished CNV area. Genetic ablation of OPN also significantly suppressed CNV area compared with wild-type mice. OPN was immunopositive in the CNV lesions and co-localized with infiltrated macrophages. Collectively these findings demonstrate a significant role of OPN in the development of CNV. OPN blockade may be considered further therapeutic potential for age-related macular degeneration.

Research Products

• [Journal Article] Non-targeted siRNA suppresses laser-induced choroidal neovascularization (2010)
  • Author(s): Shikari M, Tokoro M, Itaya M, Nozaki M, Ogura Y
  • Journal Title: Invest Ophthalmol Vis Sci Volume: 51巻 Pages: 3820-3824
  • Peer Reviewed
• [Journal Article] Non-targeted siRNA suppresses laser-induced choroidal neovascularization. (2010)
  • Author(s): Ashikari M, Tokoro M, Itaya M, Nozaki M, Ogura Y
  • Journal Title: Invest Ophthalmol Vis Sci Volume: 51 Pages: 3820-3824
  • Peer Reviewed
• [Journal Article] Non-targeted siRNA suppresses laser-induced choroidal neovascularization (2010)
  • Author(s): Ashikari M, Tokoro M, Itaya M, Nozaki M, Ogura Y
  • Journal Title: Invest Ophthalmol Vis Sci (Epub)
  • Peer Reviewed
• [Journal Article] CCR3 is a target for age-related macular degeneration diagnosis and therapy (2009)
  • Author(s): Takeda A, Baffi JZ, Kleinman ME, Cho WG, Nozaki M, Yamada K, Kaneko H, Albuquerque RJ, Dridi S, Saito K, Raisler BJ, Budd SJ, Geisen P, Munitz A, Ambati BK, Green MG, Ishibashi T, Wright JD, Humbles AA, Gerard CJ, Ogura Y, Pan Y, Smith JR, Grisanti S, Hartnett ME, Rothenberg ME, Ambati J
  • Journal Title: Nature Volume: 460巻 Pages: 225-230
  • Peer Reviewed
• [Journal Article] CCR3 is a target for age-related macular degeneration diagnosis and therapy (2009)
  • Author(s): Takeda A, Nozaki M, Ogura Y, et al
  • Journal Title: Nature 460 Pages: 225-230
  • Peer Reviewed
• [Journal Article] Small interfering RNA-induced TLR3 activation inhibits blood and lymphatic vessel growth (2009)
  • Author(s): Cho WG, Nozaki M, et al
  • Journal Title: Proc Natl Acad Sci USA 106 Pages: 7137-7142
  • Peer Reviewed
• [Presentation] Anti-angiogenic effct of IFN-gamma and IL-12 on laser-induced choroidal neovascularizationmodel in mice (2011)
  • Author(s): Masayuki Ashikari, Miho Nozaki, Takeshi Mizutani, Yuichiro Ogura
  • Organizer: ARVO 2011
  • Place of Presentation: フォートローダーデール(アメリカ)
• [Presentation] Anti-angiogenic effect of fidarestat on laser-induced choroidal neovascularizationin mice (2011)
  • Author(s): Miho Nozaki, Atsushi Nakajima, Nobutaka Morimoto, Noriaki Kato, Yuichiro Ogura
  • Organizer: ARVO 2011
  • Place of Presentation: フォートローダーデール(アメリカ)
• [Presentation] Oral Anti-Cytokine Therapy for AMD : Fidarestat Suppresses Laser-Induced Choroidal Neovascularization in Mice. (2010)
  • Author(s): Sugitani K, Nozaki M, Nakajima A, Morimoto N, Kato N, Ogura Y
  • Organizer: ARVO (Annual meeting of the Association for Research in Vision and Ophthalmology)
  • Place of Presentation: ブロワードコンベンションセンター(米国)
  • Year and Date: 2010-05-05
• [Presentation] CCR3 antagonist suppresses laser-induced choroidal neovascularization in mice (2010)
  • Author(s): Masayuki Ashikari, Mayumi Tokoro, Miho Nozaki, Yuichiro Ogura
  • Organizer: Euretina
  • Place of Presentation: パリ(フランス)
• [Presentation] オステオポンチン阻害による脈絡膜新生血管抑制 (2009)
  • Author(s): 所真由美, 野崎実穂, 他
  • Organizer: 第113回日本眼科学会総会
  • Place of Presentation: 東京国際フォーラム(東京)
  • Year and Date: 2009-04-16