Investigation of ANGPTL2 involvement in pathogenesis of age-related macular degeneration.

• Project/Area Number: 25462734
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Keio University
• Principal Investigator: HIRASAWA MANABU 慶應義塾大学, 医学部, 研究員 (80365345)
• Co-Investigator(Kenkyū-buntansha): OZAWA YOKO 慶應義塾大学, 医学部, 講師 (90265885)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: アンギオポイエチン様タンパク / 加齢黄斑変性 / 脈絡膜新生血管 / マクロファージ / アンギオポイエチン様蛋白 / 炎症性サイトカイン

Outline of Final Research Achievements

ANGPTL2 was localized at lesion of laser-induced choroidal neovascularization in mice, and reduction of CNV volume and CNV-induced pro-inflammatory mediators were observed at ANGPTL2 deficient mice, indicating involvement of ANGPTL2 in CNV pathogenesis.
In bone marrow transplantation model, both ANGPTL2 from retinal tissue and macrophage participated CNV development. In vitro study, phosphorylation of NF-κB and ERK1/2, acceleration of pro-inflammatory mediators, and macrophage migration were driven by recombinant ANGPTL2; suppressed by integrin α4 and/or β2 neutralizing antibody. ANGPTL2 and its signal induction might be new therapeutic target against age-related macular degeneration.

Research Products

• [Journal Article] Angiopoietin-like protein 2 is a multistep regulator of inflammatory neovascularization in a murine model of age-related macular degeneration. (2016)
  • Author(s): M. Hirasawa, K. Takubo, H. Osada, S. Miyake, E. Toda, M. Endo, K. Umezawa, K. Tsubota, Y. Oike and Y. Ozawa
  • Journal Title: J. Biol. Chem. Volume: 291 Issue: 14 Pages: 7373-7385
  • DOI: 10.1074/jbc.m115.710186
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 着色非球面多焦点乱視矯正眼内レンズ（SND1T3，SND1T4，SND1T5，SND1T6）の白内障摘出眼を対象とした臨床試験成績 (2015)
  • Author(s): 中村 邦彦，ビッセン宮島弘子，林 研，吉野 真未，平沢 学，桝本 美樹，瀧本 峰洋，堀川 久美，前田 直之
  • Journal Title: 日本眼科学会雑誌 Volume: 119 Pages: 7-15
  • Peer Reviewed
• [Presentation] Angiopoietin-like protein 2 の加齢黄斑変性における役割 (2016)
  • Author(s): 平沢学, 田久保圭誉, 長田秀斗, 三宅誠司, 戸田枝里子, 遠藤元誉, 梅沢一夫, 坪田一男, 尾池雄一, 小沢洋子
  • Organizer: 第16回日本抗加齢医学会総会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-06-10
• [Presentation] Postoperative Measurement of the Diameter of Femtosecond Laser-created Anterior Capsulotomy by Using the Implanted Intraocular Lens as a Reference Point (2015)
  • Author(s): M. Hirasawa, K. Minami, R. Yumiyama, S. Ooki, H. Bissen-Miyajima
  • Organizer: Asia-ARVO 2015
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2015-02-16 – 2015-02-19
• [Presentation] 多焦点トーリック眼内レンズの初期臨床成績 (2015)
  • Author(s): 平沢 学、ビッセン宮島弘子、大木伸一、中村邦彦
  • Organizer: 第38回 日本眼科手術学会
  • Place of Presentation: 京都国際会議場
  • Year and Date: 2015-01-30 – 2015-02-01
• [Presentation] 着色非球面+2.5D近方加入多焦点眼内レンズSN6AD2(SV25TO)の臨床試験成績 (2014)
  • Author(s): 平沢 学、ビッセン宮島弘子、林 研、吉野真未、中村邦彦、吉田起章、桝本美樹、佐々木博司
  • Organizer: 第68回日本臨床眼科学会
  • Place of Presentation: 神戸ポートピアホテル
  • Year and Date: 2014-11-13 – 2014-11-16
• [Presentation] Comparison between toric and non-toric intraocular lens implantation in eyes with corneal astigmatisms (2014)
  • Author(s): M. Hirasawa,H. BissenMiyajima Y. Inoue T. Nishimura H. Takehara K. Nishikawa
  • Organizer: European Society of Cataract & Refractive Surgeons Annual Meeting
  • Place of Presentation: Excel London,London,イギリス
  • Year and Date: 2014-09-12 – 2014-09-17
• [Presentation] Long-term rotational stability of micro-incision hydrophobic acrylic aspheric toric intraocular lens in a Japanese multicenter study (2014)
  • Author(s): H. Bissen-Miyajima, K. Negishi O. Hieda M. Hirasawa H. Torii K. Yamamura S. Kinoshita
  • Organizer: European Society of Cataract & Refractive Surgeons Annual Meeting
  • Place of Presentation: Excel London,London,イギリス
  • Year and Date: 2014-09-12 – 2014-09-17
• [Presentation] The clinical outcomes of apodized diffractive +3.0 D multifocal toric IOL (2014)
  • Author(s): K. Nakamura, H. BissenMiyajima K. Hayashi M. Hirasawa M. Matsumoto M. Takimoto N. Maeda
  • Organizer: European Society of Cataract & Refractive Surgeons Annual Meeting
  • Place of Presentation: Excel London,London,イギリス
  • Year and Date: 2014-09-12 – 2014-09-17
• [Presentation] フェムトセカンドレーザー白内障手術の基礎と臨床 (2014)
  • Author(s): 平沢学
  • Organizer: 第29回 JSCRS学術総会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2014-07-11 – 2014-07-13
  • Invited
• [Presentation] 白内障眼に対するトーリック眼内レンズ挿入効果の多施設後ろ向き研究 (2014)
  • Author(s): 平沢学、ビッセン宮島弘子、大木伸一、井上康、竹原弘泰、西村知久、西川久美子
  • Organizer: 第29回 JSCRS学術総会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2014-07-11 – 2014-07-13
• [Presentation] マウス脈絡膜新生血管モデルにおけるAngiopoietin-like protein 2 の役割 (2014)
  • Author(s): 小沢洋子 平沢学 田久保圭誉 三宅誠司 梅沢一夫 尾池雄一 坪田一男
  • Organizer: 第14回日本抗加齢学会総会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2014-06-06 – 2014-06-08
• [Presentation] 脈絡膜新生血管モデルにおけるAngiopoietin-like 2の関与 (2013)
  • Author(s): 平沢学
  • Organizer: 第117回日本眼科学会総会
  • Place of Presentation: 東京国際フォーラム（東京都千代田区）
• [Presentation] Involvement of Angiopoietin-like protein 2 in Laser-induced Choroidal Neovascularization (2013)
  • Author(s): Manabu Hirasawa
  • Organizer: Association for Research in Vision and Ophthalmology
  • Place of Presentation: Seatle, USA