Zhou Yedi, Yoshida Shigeo, Kubo Yuki, Yoshimura Takeru, Kobayashi Yoshiyuki, Nakama Takahito, Yamaguchi Muneo, Ishikawa Keijiro, Oshima Yuji, Ishibashi Tatsuro
Department of Ophthalmology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812‑8582, Japan.
Mol Med Rep. 2017 Jun;15(6):3949-3956. doi: 10.3892/mmr.2017.6491. Epub 2017 Apr 20.
Choroidal neovascularization (CNV) is a serious complication of age‑related macular degeneration. The aim of the present study was to investigate the expression and distribution of M1 and M2 macrophages in a laser‑induced CNV adult mouse model. The mRNA expression levels of M1, M2 and pan macrophage markers, and macrophage‑associated angiogenic cytokines, were determined by reverse transcription‑quantitative polymerase chain reaction. Immunofluorescence studies were performed to determine the location of the macrophages. The expression levels of M1 macrophage markers increased to a greater extent compared with M2 markers in the retinal pigment epithelium (RPE)‑choroid complexes following laser photocoagulation. By contrast, the expression levels of M2 macrophage markers increased primarily in the retinas. Immunofluorescence studies revealed that the increased number of cluster of differentiation (CD)206‑positive cells were located primarily in the retina, whereas the CD80‑positive cells were located around the site of CNVs in the RPE‑choroid. In addition, the M1‑associated cytokines increased to a greater extent in the RPE‑choroid complexes, whereas the M2‑associated cytokines were highly expressed in the retinas. These findings indicate that M1 and M2 macrophage numbers increased following CNV; however, the locations were different in this mouse model of laser‑induced CNV. The results of the present study suggest that M1 macrophages have a more direct role in inhibiting the development of CNV.
脉络膜新生血管(CNV)是年龄相关性黄斑变性的一种严重并发症。本研究的目的是在激光诱导的CNV成年小鼠模型中研究M1和M2巨噬细胞的表达及分布情况。通过逆转录-定量聚合酶链反应测定M1、M2和泛巨噬细胞标志物以及巨噬细胞相关血管生成细胞因子的mRNA表达水平。进行免疫荧光研究以确定巨噬细胞的位置。激光光凝后,视网膜色素上皮(RPE)-脉络膜复合体中M1巨噬细胞标志物的表达水平相比M2标志物有更大程度的升高。相比之下,M2巨噬细胞标志物的表达水平主要在视网膜中升高。免疫荧光研究显示,分化簇(CD)206阳性细胞数量增加主要位于视网膜,而CD80阳性细胞位于RPE-脉络膜中CNV部位周围。此外,RPE-脉络膜复合体中与M1相关的细胞因子升高幅度更大,而与M2相关的细胞因子在视网膜中高表达。这些发现表明CNV后M1和M2巨噬细胞数量增加;然而,在这个激光诱导的CNV小鼠模型中它们的位置不同。本研究结果提示M1巨噬细胞在抑制CNV发展中起更直接的作用。