Investigation of roles in retinal angiogenesis and pathway of SIRT1 activation.

• Project/Area Number: 26861449
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Ophthalmology
• Research Institution: Kobe University
• Principal Investigator: Matsumiya Wataru 神戸大学, 医学研究科, 医学研究員 (30707120)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: 網膜血管新生 / SIRT1 / ｃAMP / MRP4 / 病的血管新生 / 加齢性変化 / ノックアウトマウス / 網膜血管形成 / cAMP

Outline of Final Research Achievements

This study aims to investigate pathway of SIRT1 activation and functions of SIRT1 and MRP4 as cAMP transporter in pathological retinal angiogenesis and in age-related alterations .In vitro, it was shown that elevation of cAMP by Forskolin could induce activation of SIRT1 expression. In OIR model, the severity of retinopathy in P17 was greater in Mrp4-/- mice as compared with WT mice.The primary cause of exacerbated retinopathy in Mrp4-/- mice may be due to enhanced retinal vascular obliteration. Mrp4 might have a suppressive role in pathological retinal angiogenesis. Moreover, recovery from retinopathy in P28 might be better in WT mice as compared with Mrp4-/-. On the other hands, Mrp4 deficiency does not exert any noticeable influence on age-related retinal changes. These results suggests that Mrp4 play an important role via cAMP and SIRT1 in pathological retinal angiogenesis .

Research Products

• [Journal Article] One-year outcome of combination therapy with intravitreal aflibercept and verteporfin photodynamic therapy for polypoidal choroidal vasculopathy (2017)
  • Author(s): Matsumiya, W., Honda, S., Otsuka, K., Miki, A., Nagai, T., Imai, H.、Kusuhara,S., Nakamura, M.
  • Journal Title: Graefes Arch Clin Exp Ophthalmol Volume: 255 Issue: 3 Pages: 541-548
  • DOI: 10.1007/s00417-016-3500-1
  • Peer Reviewed
• [Journal Article] Comparison of the 12-Month Outcomes of Intravitreal Ranibizumab between Two Angiographic Subtypes of Polypoidal Choroidal Vasculopathy. (2017)
  • Author(s): Nakai, S., Honda, S., Miki, A., Matsumiya, W., Nakamura, M.
  • Journal Title: 10.1159/000455273 Volume: 237 Issue: 3 Pages: 123-127
  • DOI: 10.1159/000455273
  • Peer Reviewed
• [Journal Article] Efficacy and visual prognostic factors of intravitreal bevacizumab as needed for macular edema secondary to central retinal vein occlusion. (2014)
  • Author(s): Hirose M, Matsumiya W, Honda S, Nakamura M.
  • Journal Title: Clin Ophthalmol. Volume: Nov 19;8 Pages: 2301-2305
  • DOI: 10.2147/opth.s74888
  • NAID: 120005627291
  • Peer Reviewed / Open Access
• [Presentation] 加齢性網膜変化におけるmultidrug resistance protein 4 (Mrp4)の役割 (2016)
  • Author(s): 楠原仙太郎、延吉 章、小島恵子、松宮 亘、中村 誠
  • Organizer: 日本眼科学会
  • Place of Presentation: 仙台国際センター
  • Year and Date: 2016-04-07
• [Presentation] ポリープ状脈絡膜血管症に対するアフリベルセプト併用光線力学療法の12ヶ月成績 (2015)
  • Author(s): 松宮 亘,本田 茂,大塚 慶子,三木 明子,長井 隆行,今井 尚徳,楠原 仙太郎,中村 誠
  • Organizer: 第119回日本眼科学会総会
  • Place of Presentation: ロイトン札幌
  • Year and Date: 2015-04-16 – 2015-04-19
• [Presentation] 病的網膜血管新生におけるMrp4の役割 (2015)
  • Author(s): 楠原 仙太郎,松宮 亘,中村 誠
  • Organizer: 第119回日本眼科学会総会
  • Place of Presentation: さっぽろ芸文館
  • Year and Date: 2015-04-16 – 2015-04-19
• [Presentation] ポリープ状脈絡膜血管症に対するアフリベルセプト併用光線力学療法の6ヶ月成績 (2014)
  • Author(s): 松宮亘、本田茂、大塚慶子、三木明子、長井隆行、今井尚徳、楠原仙太郎、中村誠
  • Organizer: 第53回日本網膜硝子体学会総会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2014-11-28 – 2014-11-30
• [Presentation] 無治療の加齢黄斑変性に対する必要時投与によるAflibercept硝子体注射の6か月成績 (2014)
  • Author(s): 大塚 慶子, 松宮 亘, 三木 明子, 長井 隆行, 本田 茂, 中村 誠:
  • Organizer: 第68回日本臨床眼科学会
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2014-11-13 – 2014-11-16