Roles of Mrp4 in the development of diabetic retinopathy

• Project/Area Number: 15K10865
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Ophthalmology
• Research Institution: Kobe University
• Principal Investigator: KUSUHARA SENTARO 神戸大学, 医学研究科, 講師 (40437463)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 糖尿病 / 網膜 / Mrp4 / トランスポーター / 糖尿病網膜症 / 神経変性 / イメージング / MRP4 / ABCトランスポーター

Outline of Final Research Achievements

Multidrug resistance protein 4 (Mrp4) knockout mice showed a significantly lower retinal vascular density compered with wildtype mice under streptozotocin-induced hyperglycemia. InsCreTg; Pdk1flox/flox mice exhibited thinning of laminin and decrease in the number of retinal nerve fibers prior to obvious manifestations of retinal microvascular abnormality. To evaluate the abnormality of retinal cells in an early stage of diabetes, in vivo mouse retinal imaging system with two-photon microscopy was established. These results seem to be helpful for elucidating the pathogenesis of diabetic retinopathy.

Research Products

• [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
• [Presentation] Structural changes in the inner retina assessed by slab en face optical coherence tomography in diabetic eyes (2018)
  • Author(s): Atsuko Katsuyama, Sentaro Kusuhara, Wataru Matsumiya, Shigeru Honda, Makoto Nakamura
  • Organizer: ARVO 2018 annual meeting
  • Int'l Joint Research
• [Presentation] 遺伝子改変マウスで糖尿病網膜症を再現できるか？ (2016)
  • Author(s): 楠原仙太郎
  • Organizer: 第22回日本日本糖尿病眼学会総会
  • Place of Presentation: 仙台市
  • Year and Date: 2016-10-07
  • Invited
• [Presentation] Mrp4 deficiency has no apparent effect on age-related changes of the mouse retina (2016)
  • Author(s): Sentaro Kusuhara, Sho Nobuyoshi, Keiko Kojima, Wataru Matsumiya, Makoto Nakamura
  • Organizer: ARVO 2016 Annual meeting
  • Place of Presentation: シアトル
  • Year and Date: 2016-05-01
  • Int'l Joint Research
• [Presentation] Mrp4 deficiency has no apparent effect on age-related changes of the mouse retina (2016)
  • Author(s): Sentaro Kusuhara, Sho Nobuyoshi, Keiko Kojima, Wataru Matsumiya, Makoto Nakamura
  • Organizer: the ARVO 2016 Annual Meeting
  • Place of Presentation: シアトル、米国
  • Year and Date: 2016-05-01
  • Int'l Joint Research
• [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: 第120回日本眼科学会総会
  • Place of Presentation: 仙台市
  • Year and Date: 2016-04-07
• [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: 第120会日本眼科学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2016-04-07