巨噬细胞 Tie2 信号介导的自噬在激光诱导脉络膜新生血管中的重要作用。

Essential contribution of macrophage Tie2 signal mediated autophagy in laser-induced choroidal neovascularization.

机构信息

Department of Ophthalmology, The First Affiliated Hospital of Soochow University, Shizi Street 188, Suzhou, 215006, Jiangsu Province, PR China.

出版信息

Exp Eye Res. 2020 Apr;193:107972. doi: 10.1016/j.exer.2020.107972. Epub 2020 Feb 12.

DOI:10.1016/j.exer.2020.107972

PMID:32059975

Abstract

Autophagy plays critical roles in various ocular diseases, including age-related macular degeneration (AMD). Tie2-expressing macrophages (TEMs) play crucial roles in angiogenesis. To investigate the role of TEMs and autophagy in the development of AMD, we employed macrophage-specific Tie2 knockout mice and used a laser-induced choroidal neovascularization (CNV). The results showed that TEMs can promote CNV formation by up-regulating the level of autophagy. These results were further verified by in vitro cell experiments that peritoneal macrophages from Tie2 knockout mice can inhibit the expression of autophagy-related factors and inhibit the expression of angiogenic factor of VEGF by activating AMPK signaling pathway. Our results suggest that TEMs and macrophage Tie2 signal mediated-autophagy play critical role in experimental CNV, and they may be novel preventive targets for AMD treatment.

摘要

自噬在各种眼部疾病中起着关键作用，包括年龄相关性黄斑变性（AMD）。表达 Tie2 的巨噬细胞（TEMs）在血管生成中起着至关重要的作用。为了研究 TEMs 和自噬在 AMD 发展中的作用，我们使用了巨噬细胞特异性 Tie2 敲除小鼠，并采用激光诱导脉络膜新生血管（CNV）。结果表明，TEMs 通过上调自噬水平促进 CNV 形成。这些结果通过体外细胞实验进一步得到验证，即从 Tie2 敲除小鼠中分离的腹腔巨噬细胞可以通过激活 AMPK 信号通路抑制自噬相关因子的表达，并抑制血管内皮生长因子（VEGF）等血管生成因子的表达。我们的结果表明，TEMs 和巨噬细胞 Tie2 信号介导的自噬在实验性 CNV 中起着关键作用，它们可能是 AMD 治疗的新的预防靶点。