Myeloid lineage contributes to pathological choroidal neovascularization formation via SOCS3.
Myeloid lineage contributes to pathological choroidal neovascularization formation via SOCS3.
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DOI：
10.1016/j.ebiom.2021.103632
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发表时间：
2021-11
期刊：
影响因子：
11.1
通讯作者：
Sun Y
中科院分区：
文献类型：
--
作者：
Wang T;Zhou P;Xie X;Tomita Y;Cho S;Tsirukis D;Lam E;Luo HR;Sun Y
新生血管性年龄相关性黄斑变性（nAMD）中的病理性新生血管形成是老年人视力丧失的主要原因。越来越多的证据表明，骨髓谱系细胞在控制病理性内皮形成中发挥重要作用。细胞因子信号传导 3 (SOCS3) 通路抑制因子与新血管形成有关。我们利用激光诱导脉络膜新生血管 (CNV) 小鼠模型来研究人类 AMD 的新生血管方面。在几种细胞谱系报告小鼠、骨髓嵌合小鼠和 Socs3 功能丧失（敲除）和功能获得（过度表达）小鼠中，使用免疫组织化学、共聚焦和脉络膜外植体与骨髓源性巨噬细胞培养基共培养来研究通过骨髓 SOCS3 形成病理性 CNV 的机制。 SOCS3 在骨髓谱系细胞中被显着诱导，这些细胞被招募到 CNV 病变区域。骨髓 Socs3 过表达抑制激光诱导的 CNV，减少骨髓谱系来源的巨噬细胞/小胶质细胞的现场募集，并减弱促炎因子的表达。此外，骨髓中的 SOCS3 调节脉络膜外植体中的离体血管萌芽，而 SOCS3 激动剂可减少体内 CNV。这些发现表明骨髓谱系细胞参与了 SOCS3 调节的病理性 CNV 形成。该项目由 NIH/NEI (R01EY030140、R01EY029238)、BrightFocus 基金会、美国健康援助基金会 (AHAF) 和波士顿儿童医院眼科基金会 (YS) 以及美国国立卫生研究院/国家心肺和血液研究所 (U01HL098166) (U01HL098166) 资助。
Pathological neovascularization in neovascular age-related macular degeneration (nAMD) is the leading cause of vision loss in the elderly. Increasing evidence shows that cells of myeloid lineage play important roles in controlling pathological endothelium formation. Suppressor of cytokine signaling 3 (SOCS3) pathway has been linked to neovascularization. We utilised a laser-induced choroidal neovascularization (CNV) mouse model to investigate the neovascular aspect of human AMD. In several cell lineage reporter mice, bone marrow chimeric mice and Socs3 loss-of-function (knockout) and gain-of-function (overexpression) mice, immunohistochemistry, confocal, and choroidal explant co-culture with bone marrow-derived macrophage medium were used to study the mechanisms underlying pathological CNV formation via myeloid SOCS3. SOCS3 was significantly induced in myeloid lineage cells, which were recruited into the CNV lesion area. Myeloid Socs3 overexpression inhibited laser-induced CNV, reduced myeloid lineage-derived macrophage/microglia recruitment onsite, and attenuated pro-inflammatory factor expression. Moreover, SOCS3 in myeloid regulated vascular sprouting ex vivo in choroid explants and SOCS3 agonist reduced in vivo CNV. These findings suggest that myeloid lineage cells contributed to pathological CNV formation regulated by SOCS3. This project was funded by NIH/NEI (R01EY030140, R01EY029238), BrightFocus Foundation, American Health Assistance Foundation (AHAF), and Boston Children's Hospital Ophthalmology Foundation for YS and the National Institutes of Health/National Heart, Lung and Blood Institute (U01HL098166) for PZ.
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影响因子：
56.9
作者：
Asahara, T;Murohara, T;Isner, JM
通讯作者：
Isner, JM
影响因子：
20.3
作者：
Bhattacharya, V;McSweeney, PA;Wu, MHD
通讯作者：
Wu, MHD
DOI：
10.4049/jimmunol.0903563
发表时间：
2010-08-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Akhtar LN;Qin H;Muldowney MT;Yanagisawa LL;Kutsch O;Clements JE;Benveniste EN
通讯作者：
Benveniste EN
影响因子：
3
作者：
Clausen, BE;Burkhardt, C;Förster, I
通讯作者：
Förster, I
影响因子：
2
作者：
Hou, Hui-Yuan;Wang, Yu-Sheng;Liu, Jin-Ping
通讯作者：
Liu, Jin-Ping