Macrophages are involved in choroidal neovascularization (CNV). The mechanistic target of rapamycin complex 1 (mTORC1) is a central cell regulator, but mTORC1 function in macrophages in CNV is not fully understood. We explored the effect of mTORC1 pathway regulation on macrophages in CNV. A laser-induced murine CNV model was performed. Expression of phospho-S6 and F4/80 in CNV lesions was analyzed by immunofluorescence. Macrophages in CNV lesions were found at 1 day after laser treatment, reached a peak at 5 days, and decreased at 7 and 14 days. mTORC1 activity of cells in CNV lesions was increased from 3 to 7 days, and deceased at 14 days. Most infiltrating macrophages in CNV lesions had strong mTORC1 activity at 3 and 5 days that subsequently decreased. In vitro, THP-1 macrophages were polarized to M1 or M2 with rapamycin or siRNA treatment. The human retinal pigment epithelium (RPE) cell line ARPE-19 was co-cultured with macrophages. Cytokine expression of macrophages and ARPE-19 cells was detected by quantitative PCR. Inhibiting mTORC1 activity of macrophages reduced M1 and strengthened M2, which was reversed by mTORC1 hyperactivation. Both M1 and M2 macrophages induced RPE cells to express less PEDF and more MMP9, IL-1β and MCP-1. Inhibiting or enhancing mTORC1 activity of macrophages changed cytokine expression of RPE cells. Together, we demonstrated that macrophage functions in CNV were regulated partly by the mTORC1 pathway, and mTORC1 activity of macrophages influenced the expression of cytokines that are associated with CNV development in RPE cells. This study provides more understanding about the regulatory mechanism of macrophages in CNV.

中文翻译：

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mTORC1信号通路调节脉络膜新生血管中的巨噬细胞。

巨噬细胞参与脉络膜新生血管形成（CNV）。雷帕霉素复合物1（mTORC1）的机械目标是中央细胞调节剂，但尚不完全了解CNV中巨噬细胞中的mTORC1功能。我们探讨了mTORC1通路调节对CNV中巨噬细胞的影响。进行了激光诱导的小鼠CNV模型。通过免疫荧光分析CNV病变中磷酸化S6和F4 / 80的表达。激光治疗后第1天发现CNV病变中的巨噬细胞，第5天达到峰值，第7天和14天下降。CNV病变中细胞的mTORC1活性从3天增加到7天，并在14天时死亡。CNV病变中大多数浸润性巨噬细胞在第3天和第5天具有很强的mTORC1活性，随后下降。在体外，雷帕霉素或siRNA处理可将THP-1巨噬细胞极化为M1或M2。将人类视网膜色素上皮（RPE）细胞系ARPE-19与巨噬细胞共培养。通过定量PCR检测巨噬细胞和ARPE-19细胞的细胞因子表达。抑制巨噬细胞的mTORC1活性可降低M1并增强M2，这可通过mTORC1过度活化来逆转。M1和M2巨噬细胞均诱导RPE细胞表达更少的PEDF和更多的MMP9，IL-1β和MCP-1。抑制或增强巨噬细胞的mTORC1活性改变了RPE细胞的细胞因子表达。在一起，我们证明了CNV中的巨噬细胞功能部分受mTORC1途径调节，而巨噬细胞的mTORC1活性影响与RPE细胞中CNV发育相关的细胞因子的表达。这项研究使人们对CNV中巨噬细胞的调控机制有了更多的了解。