Development of a new mouse model of diabetic retinopathy and establishment of novel concepts for drug discovery

• Project/Area Number: 15H04997
• 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 名古屋市立大学, 大学院医学研究科, 教授 (70191963)
• Co-Investigator(Kenkyū-buntansha): 野崎 実穂 名古屋市立大学, 大学院医学研究科, 講師 (00295601) ; 安川 力 名古屋市立大学, 大学院医学研究科, 准教授 (00324632) ; 植村 明嘉 名古屋市立大学, 大学院医学研究科, 教授 (30373278) ; 平野 佳男 名古屋市立大学, 医学(系)研究科(研究院), 助教 (40405163) ; 吉田 宗徳 名古屋市立大学, 大学院医学研究科, 准教授 (60273447)
• Research Collaborator: Koh Gou Young ; Kim Pilhan
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000); Fiscal Year 2017: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2016: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2015: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
• Keywords: 糖尿病網膜症 / ペリサイト / 内皮細胞 / マクロファージ / VEGF-A / PlGF / Angiopoietin-2 / 炎症 / 線維化 / イメージング / VEGF

Outline of Final Research Achievements

In diabetic retinopathy (DR), dropout of pericytes from capillary walls is assumed to initiate various vascular dysfunctions, including blood-retina barrier breakdown. However, hyperglycemic mice fail to reproduce retinal pathology characteristic of DR. In this research project, we established a new mouse model of DR in adult mice, by transiently inhibiting pericyte recruitment to developing retinal vessels during neonatal periods following single intraperitoneal injections of an anti-PDGFRβ antibody. Furthermore, we uncovered that endothelial cells and macrophages formed a cycle of vessel damage via VEGF-A, PlGF, and angiopoietin-2 in pericyte-deficient retinal vessels.

Research Products

• [Int'l Joint Research] KAIST(韓国)
• [Journal Article] Sustained inflammation after pericyte depletion induces irreversible blood-retina barrier breakdown (2017)
  • Author(s): Ogura S, Kurata K, Hattori Y, Takase H, Ishiguro-Oonuma T, Hwang Y, Ahn S, Park I, Ikeda W, Kusuhara S, Fukushima Y, Nara H, Sakai H, Fujiwara T, Matsushita J, Ema M, Hirashima M, Minami T, Shibuya M, Takakura N, Kim P, Miyata T, Ogura Y, Uemura A
  • Journal Title: JCI Insight Volume: 2 Issue: 3
  • DOI: 10.1172/jci.insight.90905
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant