Roles of neurovascular unit in diabetic retinal neurodegeneration

• Project/Area Number: 18K09409
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56060:Ophthalmology-related
• Research Institution: Kobe University
• Principal Investigator: Kusuhara Sentaro 神戸大学, 医学研究科, 講師 (40437463)
• Co-Investigator(Kenkyū-buntansha): 淺原 俊一郎 神戸大学, 医学部附属病院, 助教 (00570342) ; 橘 吉寿 神戸大学, 医学研究科, 准教授 (50373197)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 糖尿病網膜症 / アストロサイト / neurovascular unit / in vivoイメージング / 糖尿病 / 網膜変性 / イメージング

Outline of Final Research Achievements

We evaluated the damage to neurovascular unit and performed in vivo two-photon imaging of retinal glial cells in diabetic (InsCreTg; Pdk1flox/flox) mice. Immunohistochemistry disclosed that microglial activation as well as decrease in laminin thickness and ganglion cell axons proceed other cellular and extracellular matrix events in diabetic mouse retinas. Improvement of optical system including contact lens enabled high-resolution in vivo retinal imaging. Using this imaging system, we observed microglia migrating around retinal vessels and astrocytes with its processes extending towards them and detected leukocytes slowly moving in the retinal vessel lumen.

Academic Significance and Societal Importance of the Research Achievements

糖尿病網膜神経変性は検眼鏡的に明らかな糖尿病網膜症が出現する以前から網膜内層に生じている神経変性であり、細胞レベルではこの段階でneurovascular unitの障害が生じていると考えられている。本研究によって糖尿病早期における細胞レベルでの網膜機能評価を可能にするする技術が確立されれば、早期からのneurovascular unit障害の評価が可能となり、結果的に糖尿病網膜症による失明予防に大いに貢献できると考える。

Research Products

• [Journal Article] En face slab optical coherence tomography imaging successfully monitors progressive degenerative changes in the innermost layer of the diabetic retina (2020)
  • Author(s): Katsuyama Atsuko、Kusuhara Sentaro、Asahara Shun-Ichiro、Nakai Shun-Ichiro、Mori Sotaro、Matsumiya Wataru、Miki Akiko、Kurimoto Takuji、Imai Hisanori、Kido Yoshiaki、Ogawa Wataru、Nakamura Makoto
  • Journal Title: BMJ Open Diabetes Research & Care Volume: 8 Issue: 1 Pages: e001120-e001120
  • DOI: 10.1136/bmjdrc-2019-001120
  • NAID: 120006863549
  • Peer Reviewed / Open Access
• [Journal Article] Pathophysiology of Diabetic Retinopathy: The Old and the New (2018)
  • Author(s): Kusuhara Sentaro、Fukushima Yoko、Ogura Shuntaro、Inoue Naomi、Uemura Akiyoshi
  • Journal Title: Diabetes & Metabolism Journal Volume: 42 Issue: 5 Pages: 364-364
  • DOI: 10.4093/dmj.2018.0182
  • Peer Reviewed / Open Access
• [Presentation] 糖尿病網膜におけるin vivo functional imagingに向けて (2021)
  • Author(s): 楠原 仙太郎
  • Organizer: 第125回日本眼科学会総会 イブニングセミナー2
• [Presentation] 膵β細胞特異的Pdk1コンディショナルノックアウトマウスにおける糖尿病性網膜変化 (2020)
  • Author(s): 勝山敦子、楠原仙太郎、金景佑、西庄龍東、松宮亘、中村誠
  • Organizer: 第124回日本眼科学会総会
• [Presentation] 光干渉断層計slab en face像を用いた糖尿病網膜内層構造変化の評価 (2018)
  • Author(s): 勝山敦子、楠原仙太郎、松宮 亘、本田 茂、中村 誠
  • Organizer: 第122回日本眼科学会総会
• [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