Establishment of a novel experimental model of retinal pericyte deletion for accelerating the development of therapeutic agents for diabetic retinopathy

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06604
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47040:Pharmacology-related
• Research Institution: Kitasato University
• Principal Investigator: Nakahara Tsutomu 北里大学, 薬学部, 教授 (10296519)
• Co-Investigator(Kenkyū-buntansha): 森田 茜 北里大学, 薬学部, 助教 (00828072)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 網膜血管 / 網膜症 / 内皮細胞 / ペリサイト

Outline of Final Research Achievements

Imatinib, a drug for the treatment of chronic myelogenous leukemia, has inhibitory activity on PDGF receptor β. The present study showed that in neonatal rats treated with imatinib, degeneration of retinal capillary pericytes occurred rapidly, and neovascular tufts formed at the site within a week. VEGF receptor 2 was expressed in neovascular tufts and surrounding neovascular vessels and neurons, and VEGF was expressed in retinal ganglion cells. Inhibition of VEGF receptors regressed the neovascular tufts. Thus, VEGF signaling pathway plays an important role in the formation of neovascular tufts following imatinib-induced deletion of retinal capillary pericytes, showing similarities with the vascular abnormalities that occur in human diabetic retinopathy.

Free Research Field

薬理学

Academic Significance and Societal Importance of the Research Achievements

糖尿病網膜症は失明の危険性が極めて高く、Quality of lifeを著しく低下させる疾患として、その病態の解明と予防法・治療法の確立が待ち望まれている。一方で基礎研究に汎用されるマウス・ラットでは、糖尿病を発症させて長期間飼育しても、網膜において血管内皮細胞及びペリサイトの脱落などのヒトの糖尿病網膜症と類似した網膜血管病変が生じにくいという問題点がある。薬物を使用する簡便な方法によりヒトの糖尿病時に生じる網膜血管病変を再現することができれば糖尿病網膜症の病態解明とそれに対する予防／治療薬スクリーニングの飛躍的な効率化に繋がり得る。