Development of New Drug Delivery Systems to Target Vascular Endothelial Growth Factor in Age -Related Macular Degeneration

• Project/Area Number: 18390471
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Nagoya City University
• Principal Investigator: OGURA Yuichiro Nagoya City University, 大学院・医学研究科, 教授 (70191963)
• Co-Investigator(Kenkyū-buntansha): YOSHIDA Munenori 名古屋市立大学, 大学院・医学研究科, 准教授 (60273447) ; SAKURAI Eiji 名古屋市立大学, 大学院・医学研究科, 講師 (30305528) ; YASUKAWA Tsutomu 名古屋市立大学, 大学院・医学研究科, 准教授 (00324632)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,080,000 (Direct Cost: ¥15,200,000、Indirect Cost: ¥2,880,000); Fiscal Year 2008: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000); Fiscal Year 2007: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000); Fiscal Year 2006: ¥5,600,000 (Direct Cost: ¥5,600,000)
• Keywords: 眼細胞生物学 / 加齢黄斑変性 / ドラッグデリバリーシステム / ドルーゼン / 脈絡膜新生血管 / 家兔 / 動物モデル / 網膜色素上皮 / 脈略膜新生血管 / 家兎 / siRNA / ドラッグターゲティング

Research Abstract

加齢黄斑変性は成人失明の主要原因である。これまで光線力学的療法が標準的な治療法であったが最近、抗血管内皮増殖因子(VEGF)療法の有効性が欧米で示され、国内でも治療の選択肢となってくるが、4~6週間ごとの硝子体内注射を必要とするため合併症が懸念される。注射回数を減らして有効濃度を保てるようなドラッグデリバリーシステムの開発のため、ゼラチンハイドロゲルシートを作製したところ、ポリイオンコンプレックスを形成して抗体を結合できることがわかった。またsiRNAを産生するプラスミドをマウスの静脈内に大量投与すると網膜内に導入可能であることがわかった。VEGF発現に関与しているICAM-1の発現を抑えるsiRNA導入で培養細胞におけるICAM-1の発現を抑制することができた。今後、大型動物における抗VEGF抗体の徐放試験、siRNA導入試験を進めていく。

Research Products

• [Journal Article] Early-onset macular holes following ruptured retinal arterial macroaneurysms (2008)
  • Author(s): Sato R, Yasukawa T, Hirano Y, Ogura Y
  • Journal Title: Graefes Arch Clin Exp Ophthalmol 246 Pages: 1779-1782
  • Peer Reviewed
• [Journal Article] Suppressive effect of short-interfering RNA on hyperglycemia-induced expression of intercellular adhesion molecule-1 on cultured vascular endothelial cells (2008)
  • Author(s): Takase A, Yasukawa T, Kato A, Ogura Y
  • Journal Title: Graefes Arch Clin Exp Ophthalmol 246 Pages: 989-992
  • Peer Reviewed
• [Journal Article] Suppressive effect of short-interfering RNA on hyperglycemia-induced expression of intercellular adhesion molecule-1 on cultured vascular endothelial cells. (2008)
  • Author(s): Takase A
  • Journal Title: Graefes Arch Clin Exp Ophthalmol 246 Pages: 989-992
  • Peer Reviewed
• [Journal Article] Suppressive effect of short-interfering RNA on hyperglycemia-induced expression of intercellular adhesion molecule-1 on cultured vascular endothelial cells. (2008)
  • Author(s): Takase A
  • Journal Title: Graefes Arch Clin Exp Ophthalmol
  • Peer Reviewed
• [Journal Article] Glycoxidized particles mimic lipofuscin accumulation in aging eyes : a new age-related macular degeneration model in rabbits (2007)
  • Author(s): Yasukawa T, Wiedemann P, Hoffmann S, Kacza J, Eichler W, Wang YS, Nishiwaki A, Seeger J, Ogura Y
  • Journal Title: Graefes Arch Clin Exp Ophthalmol 245 Pages: 1475-1485
  • Peer Reviewed
• [Journal Article] Copper foreign body in the lens without damage of iris and lens capsule (2007)
  • Author(s): Tokoro M, Yasukawa T, Okada M, Ogura Y, Uchida S
  • Journal Title: Int Ophthalmol 27 Pages: 329-331
  • Peer Reviewed
• [Journal Article] Development of drug-delivery systems to the posterior segments of the eye (2007)
  • Author(s): Yasukawa T, Tabata Y, Kimura H, Kunou N, Ogura Y
  • Journal Title: Expert Rev Ophthalmol 2 Pages: 197-211
  • Peer Reviewed
• [Journal Article] Drug delivery from ocular implants (2006)
  • Author(s): Yasukawa T, Ogura Y, Kimura H, Sakurai E, Tabata Y
  • Journal Title: Expert Opin Drug Deliv 3 Pages: 261-273
  • Peer Reviewed
• [Journal Article] Drug delivery from ocular implants. (2006)
  • Author(s): Yasukawa T
  • Journal Title: Expert Opin Drug Deliv 3・2 Pages: 261-273
• [Presentation] Fundus autofluorescence in a rabbit age-related maoular degeneration model induced by simulation of lipofuscin accumulation. (2008)
  • Author(s): Yasukawa T
  • Organizer: 26^<th> meeting of the Club Jules Gonin
  • Place of Presentation: St. Moritz, Switzerland
  • Year and Date: 2008-09-12
• [Presentation] Suppression of ICAM-1 in Murine retina by plasmid interfering RNAs (2008)
  • Author(s): Hirano Y, Sakurai E, Matsubara A, Ogura Y
  • Organizer: 2008 Annual Meeting of the Association for Research in Vision and Ophthalmology
  • Place of Presentation: Fort Lauderdale, USA
  • Year and Date: 2008-05-01
• [Presentation] Three-dimensional spheroid culture system redifferentiates retinal pigment epithelial cells independent of number of passages (2008)
  • Author(s): Yasukawa T, Nishiwaki A, Wiedemann P, Takase A, Yafai Y, Eichler W, Bringmann A, Ogura Y
  • Organizer: 2008 Annual Meeting of the Association for Research in Vision and Ophthalmology
  • Place of Presentation: Fort Lauderdale, USA
  • Year and Date: 2008-05-01
• [Presentation] Suppression of ICAM-1 in Murine retina by plasmid small interfering RNAs. (2008)
  • Author(s): Hirano Y
  • Organizer: 2008 Annual Meeting of the Association for Research in Vision and Ophthalmology
  • Place of Presentation: Fort Lauderdale, USA
  • Year and Date: 2008-05-01
• [Presentation] Three-dimensional spheroid culture system redifferentiates retinal pigment epithelial cells independent of number of passages. (2008)
  • Author(s): Yasukawa T
  • Organizer: 2008 Annual Meeting of the Association for Research in Vision and Ophthalmology
  • Place of Presentation: Fort Lauderdale, USA
  • Year and Date: 2008-05-01
• [Presentation] Fundus autofluorescence in a rabbit age-related macular degeneration model induced by simulation of lipofuscin accumulation (2008)
  • Author(s): Yasukawa T, Wiedemann P, Hirata M, Takase A, Ogura Y
  • Organizer: 26^<th> meeting of the Club Jules Gonin
  • Place of Presentation: St. Moritz, Switzerland
• [Presentation] Long-term outcome of radiation therapy for exudative age-related macular degeneration in Japanese patients (2008)
  • Author(s): Yasukawa T, Tokoro M, Sakurai E, Yoshida M, Ogura Y
  • Organizer: Would Ophthalmology Congress(WOC)2008
  • Place of Presentation: Hong Kong, China
• [Presentation] Fundus autofluorescence in a rabbit model of age-related macular degenration induced by advanced glycation end product microspheres as imitation lipofuscin (2007)
  • Author(s): Hirata M
  • Organizer: 2007 Annual Meeting of the Association for Research in Vision and Ophthalmology
  • Place of Presentation: Fort Lauderdale, USA
  • Year and Date: 2007-05-09
• [Presentation] Drusen formation in a three-dimensional culture system of retinal pigment epithelial cells (2007)
  • Author(s): Yasukawa T, Wiedemann P, Takase A, Nishiwaki A, Hirata M, Kacza J, Yafai Y, Eichler W, Seeger J, Ogura Y
  • Organizer: 2007 Annual Meeting of the Association for Research in Vision and Ophthalmology
  • Place of Presentation: Fort Lauderdale, USA
  • Year and Date: 2007-05-07
• [Presentation] Fundus autofluorescence in a rabbit model of age-related macular degeneration induced by subretinal implantation of imitation lipofuscin (2007)
  • Author(s): Yasukawa T, Wiedemann P, Hirata M, Takase A, Kunou N, Kimura E, Eichler W, Ogura Y
  • Organizer: SOE The 16^<th> congress of the European Society of Ophthalmology
  • Place of Presentation: Wien, Austria
• [Presentation] Fundus autofluorescence in a rabbit model of age-related macular degenration induced by subretinal implantation of imitation lipofuscin (2007)
  • Author(s): Yasukawa T
  • Organizer: 2007 Annual Meeting of the European Society of Ophthalmology
  • Place of Presentation: Vienna, Austria
• [Presentation] In vitro observasion system for basal functions of retinal pigment epithelium (2006)
  • Author(s): Yasukawa T, Wiedemann P, Kacza J, Takase A, Seeger J, Ogura Y
  • Organizer: 2006 Annual Meeting of the Association for Research in Vision and Ophthalmology
  • Place of Presentation: Fort Lauderdale, USA
  • Year and Date: 2006-05-01
• [Presentation] Drusen in aging eyes : a masterpiece of retinal pigment epithelium (2006)
  • Author(s): Yasukawa T, Wiedemann P, Kacza J, Yafai Y, Eichler W, Hoffmann S, Seeger J, Ogura Y
  • Organizer: 25^<th> meeting of the Club Jules Gonin
  • Place of Presentation: Cape Town, South Africa