Interleukin-6 plays a crucial role in the development of subretinal fibrosis in a mouse model
Interleukin-6 plays a crucial role in the development of subretinal fibrosis in a mouse model
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DOI：
10.1080/09114300.2018.1451609
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发表时间：
2018-01
影响因子：
4.4
通讯作者：
Kota Sato;A. Takeda;Eiichi Hasegawa;Y. Jo;Mitsuru Arima;Y. Oshima;Yanai Ryoji;T. Nakazawa;M. Yuzawa;H. Nakashizuka;H. Shimada;K. Kimura;T. Ishibashi;K. Sonoda
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作者：
Kota Sato;A. Takeda;Eiichi Hasegawa;Y. Jo;Mitsuru Arima;Y. Oshima;Yanai Ryoji;T. Nakazawa;M. Yuzawa;H. Nakashizuka;H. Shimada;K. Kimura;T. Ishibashi;K. Sonoda
摘要视网膜下纤维化是渗出性年龄相关性黄斑变性（AMD）晚期的一个特征，可导致不可逆的视力丧失。本研究旨在阐明白细胞介素-6（IL-6）在视网膜下纤维化发生发展中的作用。用抗人IL-6抗体对渗出性AMD患者手术切除的脉络膜新生血管组织进行免疫组织化学（IHC）。在小鼠视网膜下纤维化模型中测量视网膜下纤维化的面积，其中在腹膜渗出细胞（佩奇）注射到玻璃体腔中之后注射对照小干扰RNA（siRNA）或IL-6 siRNA，或同种型对照抗体或抗IL-6受体抗体。将源自IL-6+/+或IL-6− scin −小鼠的佩奇置于IL-6+/+小鼠的视网膜下腔中。IL-6在脉络膜新生血管组织的基质层和视网膜色素上皮（RPE）层表达。IL-6敲低或阻断IL-6受体可抑制视网膜下成纤维细胞瘢痕的形成。来自IL-6− scin −小鼠的佩奇诱导的视网膜下纤维化面积小于来自IL-6+/+小鼠的佩奇诱导的视网膜下纤维化面积。结果表明，由活化的巨噬细胞表达的IL-6是促进视网膜下纤维化的关键介质。靶向IL-6和相应的信号通路将是一种有吸引力的治疗方法，不仅在脉络膜新生血管，而且在视网膜下纤维化。
Abstract Subretinal fibrosis has been recognized as a feature of an advanced stage of exudative age-related macular degeneration (AMD) that leads to irreversible loss of vision. This study was aimed at elucidating roles of interlukin-6 (IL-6) in the development of subretinal fibrosis. Immunohistochemistry (IHC) was performed with anti-human IL-6 antibody in surgically excised choroidal neovascular tissues from patients with exudative AMD. The area of subretinal fibrosis was measured in a mouse subretinal fibrosis model with injection of control small interfering RNA(siRNA) or IL-6 siRNA, or isotype control antibody or anti-IL-6 receptor antibody after peritoneal exudative cells (PECs) injection into the vitreous cavity. PECs derived from IL-6+/+ or IL-6−∕− mice were placed into the subretinal space of IL-6+/+ mice. IL-6 was expressed in the stroma and retinal pigment epithelial (RPE) layer in the choroidal neovascular tissues. IL-6 knockdown or blocking of the IL-6 receptor suppressed the formation of subretinal fibroblastic scars. The area of subretinal fibrosis induced by PECs derived from IL-6−∕− mice was less than that induced by PECs from IL-6+/+ mice. The results suggested that IL-6, expressed by activated macrophages, is a crucial mediator that promotes subretinal fibrosis. Targeting IL-6 and the corresponding signaling pathway would be an attractive therapeutic approach not only in choroidal neovascularization, but also in subretinal fibrosis.