The New Treatment Method for The Edema of Neural Tissue

• Project/Area Number: 19791283
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Ophthalmology
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: MARUYAMA Kazuichi Kyoto Prefectural University of Medicine, 附属病院, 専攻医 (10433244)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,780,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥480,000); Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2007: ¥1,700,000 (Direct Cost: ¥1,700,000)
• Keywords: 脳神経 / 免疫学 / 細胞 / 組織 / 脳・神経 / 細胞・組織

Research Abstract

本研究は、現在までに特別な治療が確立されていない神経系組織浮腫への治療に対し、リンパ管を新生させるという新しいアプローチの開発を目的としていた。SEMA(semaphoring)3Fがリンパ管を特異的に抑制することから、神経系組織である網膜内に多く存在するSEMA3Fを用い、実際にSEMA3Fが病的リンパ管を抑制できるかどうかを検討した。角膜縫合による炎症誘導モデルにおいて、recombinant SEMA3Fを結膜下投与し、角膜内に発生するリンパ管を特異的に抑制できるかどうかを検討した結果、SEMA3F投与群で有意に角膜リンパ管新生が抑制できた。また我々の研究で炎症下においてマクロファージがリンパ管を形成することを証明しているが、マクロファージにもSEMA3Fの受容体であるNRP2が発現していることを確認することできた。さらにSEMA3Fでマクロファージを刺激したところ、リンパ管関連マーカーであるLYVE-1,Podoplaninの発現がウェスタンブロットによりタンパクレベルの発現がマクロファージ上で抑制されることを発見した。

Research Products

• [Journal Article] Promotion of graft survival by vascular endothelial growth factor a neutralization after high-risk corneal transplantation (2008)
  • Author(s): Bachmann BO, Bock F, Wiegand SJ, Maruyama K, Dana MR, Kruse FE, Luetjen-Drecoll E, Cursiefen C
  • Journal Title: Arch Ophthalmol 126 Pages: 71-77
• [Journal Article] Promotion of graft survival by vascular endothelial growth factor a neutralization after high-risk corneal transplantation (2008)
  • Author(s): Bachmaiin, BO, Bock F, Wiegand SJ, Maruyama K, Dana MR, Kruse FE, Luetjen-Drecoll E, Cursiefen C
  • Journal Title: Arch Ophthalmol. 126 Pages: 71-77
  • Peer Reviewed
• [Journal Article] Decreased macrophage number and activation lead to reduced lymphatic vessel formation and contribute to impaired diabetic wound healing (2007)
  • Author(s): Maruyama K, Asai J, Ii M, Thorne T, Losordo DW, D'Amore PA
  • Journal Title: American Journal of Pathology 170(4) Pages: 1178-1191
• [Journal Article] Monocyte chemoattractant protein 1 mediates retinal detachment-induced photoreceptor apoptosis (2007)
  • Author(s): Nakazawa T, Hisatomi T, Nakazawa C, Noda K, Maruyama K, She H, Matsubara A, Miyahara S, Nakao S, Yin Y, Benowitz L, Hafezi-Moghadam A, Miller JW
  • Journal Title: Proc Natl Acad Sci USA 104(7) Pages: 2425-2430
• [Journal Article] Role of thrombospondin-1 in T cell response to ocular pigment epithelial cells (2007)
  • Author(s): Futagami Y, Sugita S, Vega J, Ishida K, Takase H, Maruyama K, Aburatani H, Mochizuki M
  • Journal Title: Journal of Immunology 178(11) Pages: 6994-7005
• [Journal Article] Decreased macrophage number and activation lead to reduced lymphatic vessel formation and contribute to impaired diabetic wound healing. (2007)
  • Author(s): Maruyama K, Asai J, Ii M, Thorne T, Losordo DW, D'Amore PA.
  • Journal Title: American Journal of Pathology 170(4) Pages: 1178-91
  • Peer Reviewed
• [Journal Article] Monocyte chemoattractant protein 1 mediates retinal detachment-induced photoreceptor apoptosis. (2007)
  • Author(s): Nakazawa T, Hisatomi T, Nakazawa C, Noda K, Maruyama K, She H, Matsubara A, Miyahara s. Nakao S, Yin Y, Benowitz L, Hafezi-Moghadam A, Miller JW.
  • Journal Title: Proc Natl Acad Sci U S A 104(7) Pages: 2425-30
  • Peer Reviewed
• [Journal Article] Role of thrombospondin-1 in T cell response to ocular pigment epithelial cells. (2007)
  • Author(s): Futagami Y, Sugita S, Vaga J, Ishid a K, Takase H, Maruyama K. Abur atani H, Mochizuki M.
  • Journal Title: Journal of Immunology 178(11) Pages: 6994-7005
  • Peer Reviewed
• [Presentation] The Effect of SEMA3F on Lymphangiogenesis in the Cornea Association Research of Vision and Ophthalmology 2008 (2008)
  • Author(s): Maruyama K, Bielenberg D, Shimizu A, Fukumoto A, Ohishi A, Klagsbrun M, D'Amore P, Kinoshita S
  • Place of Presentation: アメリカ合衆国
  • Year and Date: 2008-04-28
• [Presentation] The Effect of SEMA3F on Lymphangiogenesis in the Cornea (2008)
  • Author(s): Maruyama K, Bielenberg D, Shimizu A, Fukumoto A, Ohishi A, Klagsbrun M, D' Amore P, Kinoshita S
  • Organizer: Association Research of Vision and Ophthalmology
  • Place of Presentation: フォートローダーデール、アメリカ合衆国
  • Year and Date: 2008-04-28
• [Presentation] The Effect of SEMA3F on Lymphangiogenesis in the Cornea (2008)
  • Author(s): Maruyama K, Bielenberg D, Shimizu A, Fukumoto A, Oishi A, Klagsbrun M, D'Amore P, Kinoshita S.
  • Organizer: Association Research of Vision and Ophthalmology
  • Place of Presentation: アメリカ合衆国
  • Year and Date: 2008-04-28