Establishment of an evaluation system for anti-angiogenic drugs by visualization of pathological retinal neovascularization-specific proliferation and survival signaling molecules

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K16012
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 47040:Pharmacology-related
• Research Institution: Kitasato University
• Principal Investigator: Morita Akane 北里大学, 薬学部, 助教 (00828072)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: 血管内皮細胞 / 血管生物学

Outline of Final Research Achievements

This study aimed to visualize the status of the vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) system in proliferating endothelial cells. In 4-day-old mice, immunoreactivity for phosphorylated ERK (pERK) was detected in both vascular and non-vascular cells in the retina. The pERK immunoreactivity was markedly diminished in endothelial cells one hour after injection of the MEK inhibitor or the VEGFR tyrosine kinase inhibitor. Capillary regression occurred six hours after injection of the VEGFR inhibitor. These results suggest that reduction in pERK occurs in endothelial cells before the cell death after inhibition of VEGFR.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

本研究では、新生仔マウス網膜の新生血管において ERK が活性化している様子を in vivo において可視化し、各種阻害薬によりそのダイナミクスを解析することが可能となった。網膜の新生血管における ERK のリン酸化を可視化することは VEGF/VEGFR シグナル経路に作用する網膜血管新生抑制薬の効率的なスクリーニングに有用である。