Molecular mechanisms of ocular tissue in photodynamic therapy for age-related macular degeneration

• Project/Area Number: 23592587
• 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: MISA Suzuki 慶應義塾大学, 医学部, 特任助教 (30404966)
• Co-Investigator(Kenkyū-buntansha): YOKO Ozawa 慶應義塾大学, 医学部, 講師 (90265885)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 加齢黄斑変性 / 光線力学療法 / 抗血管新生療法 / VEGF / 脈絡膜新生血管 / AMD / PDT / 神経保護 / PDT併用抗VEGF療法 / 網膜 / 抗VEGF療法 / アポトーシス / 国際情報交流

Research Abstract

Anti-vascular endothelial growth factor (VEGF) drugs and/or photodynamic therapy (PDT) constitute current treatments targeting pathological vascular tissues in age-related macular degeneration. Concern that PDT might induce VEGF and exacerbate the disease has led us to current practice of using anti-VEGF drugs with PDT simultaneously. However, the underlying molecular mechanisms of these therapies are not well understood.
We performed PDT on normal, intact mouse retina, using a laser level below the damage threshold for normal tissue, and analyzed VEGF expression. We also studied the histological consequences of suppressing VEGF function after PDT, and examined the activation of a downstream component of the VEGF signal. The immediate and transient induction of VEGF in response to PDT is neuroprotective and is required for photoreceptor cell survival.
Combined therapy may promote photoreceptor cell death and visual function impairment, based on our results.

Research Products

• [Journal Article] Neuroprotective response after photodynamic therapy : Role of vascular endothelial growth factor (2011)
  • Author(s): Suzuki M, Ozawa Y, Kubota S, Hirasawa M, Miyake S, Noda K, Tsubota K, Kadonosono K, Ishida S
  • Journal Title: J Neuroinflammation Volume: 8 Issue: 1 Pages: 176-176
  • DOI: 10.1186/1742-2094-8-176
  • NAID: 120005372300
  • Peer Reviewed
• [Journal Article] Cyclooxygenase inhibitor improved an exudative lesion of choroidal neovascularization in age-related macular degeneration (2011)
  • Author(s): Misa Suzuki, Takayoshi Suzuki, Aoi Nagano, Manabu Hirasawa, Kenichi Sakuyama, Nobuhisa Mizuki
  • Journal Title: European journal of ophthalmology Volume: 22(3) Pages: 495-8
  • Peer Reviewed
• [Presentation] Histological changes after photodynamic therapy (PDT) combined with anti-vascular endothelial growth factor (VEGF) therapy in the mouse retina (2012)
  • Organizer: Association for Research in Vision and Ophthalmology (ARVO) 2012 Annual Meeting
  • Place of Presentation: Fort Lauderdale, Florida, USA
• [Presentation] 光線力学的療法に伴う血管内皮増殖因子の発現亢進の生物学的意義 (2012)
  • Author(s): 鈴木美砂、久保田俊介、平沢学、三宅誠二、野田航介、石田晋、小沢洋子、坪田一男
  • Organizer: 日本眼科学会
  • Place of Presentation: 東京, 日本
• [Presentation] 光線力学的療法に伴う血管内皮増殖因子の発現亢進の生物学的意義 (2012)
  • Author(s): 鈴木美砂
  • Organizer: 日本眼科学会
  • Place of Presentation: 東京
• [Presentation] Histological Changes After Photodynamic Therapy (PDT) Combined With Anti-vascular Endothelial Growth Factor (VEGF) Therapy In The Mouse Retina. (2012)
  • Author(s): Misa Suzuki, Shunsuke Kubota2,, Manabu Hirasawa, Seiji Miyake, Kousuke Noda, Kazuo Tsubota, Kazuaki Kadonosono, Susumu Ishida, Yoko Ozawa
  • Organizer: The Association for Research in Vision and Ophthalmology Annual Meeting
  • Place of Presentation: FORT LAUDERDALE, FLORIDA
• [Presentation] Neuroprotective response after photodynamic therapy : Role of vascular endothelial growth factor (2011)
  • Author(s): M. Suzuki, Y. Ozawa, S. Kubota, M. Hirasawa, S. Miyake, T. Narimatsu. K. Noda, K. Tsubota, K. Kadonosono, S. Ishida
  • Organizer: Association for Research in Vision and Ophthalmology (ARVO) 2011 Annual Meeting
  • Place of Presentation: Fort Lauderdale, Florida, USA
• [Presentation] Role of Vascular Endothelial Growth Factor Induced by Photodynamic Therapy (2011)
  • Author(s): Misa Suzuki1,2, Yoko Ozawa2, Shunsuke Kubota3, Manabu Hirasawa4, Seiji Miyake2, Toshio Narimatsu2, Kazuo Tsubota2, Kazuaki Kadonosono5, Kousuke Noda6, Susumu Ishida6
  • Organizer: ARVO Annual Meeting
  • Place of Presentation: Fort Lauderdale, Fla. USA