Department of Ophthalmology & Visual Science, Eye Institute, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai 200031, China.
Department of Ophthalmology, Jin Shan Hospital, Fudan University, Shanghai 200540, China.
Exp Eye Res. 2021 Jan;202:108353. doi: 10.1016/j.exer.2020.108353. Epub 2020 Nov 7.
Mouse Müller cells, considered as dormant retinal progenitors, often respond to retinal injury by undergoing reactive gliosis rather than displaying neural regenerative responses. Tumor necrosis factor alpha (TNFα) is a key cytokines induced after injury and implicated in mediating inflammatory and neural regenerative responses in zebrafish. To investigate the involvement of TNFα in mouse retinal injury, adult C57BL/6J mice were subjected to light damage for 14 consecutive days. TNFα was elevated in the retina of mice exposed to light damage, which induced Müller cell proliferation in vitro. Affymetrix microarray showed that, in Müller cells, TNFα induces up-regulation of inflammatory and proliferation-related genes, including NFKB2, leukemia inhibitory factor, interleukin-6, janus kinase (Jak) 1, Jak2, signal transducer and activator of transcription (Stat) 1, Stat2, mitogen-activated protein kinase (MAPK) 7, and MAP4K4 but down-regulation of neuroprogenitor genes, including Sox9, Ascl1, Wnt2 and Hes1. Blocking the Jak/Stat and MAPK pathways attenuated TNFα-induced Müller cell proliferation. These results suggest that TNFα may drive the proliferation and inflammatory response, rather than the neural regenerative potential, of mouse Müller cells.
鼠 Müller 细胞被认为是休眠的视网膜祖细胞，通常在受到视网膜损伤时通过发生反应性胶质增生来响应，而不是表现出神经再生反应。肿瘤坏死因子-α（TNFα）是损伤后诱导的关键细胞因子之一，涉及在斑马鱼中介导炎症和神经再生反应。为了研究 TNFα 在小鼠视网膜损伤中的作用，将成年 C57BL/6J 小鼠连续 14 天暴露于光损伤下。在光损伤小鼠的视网膜中 TNFα 水平升高，体外诱导 Müller 细胞增殖。Affymetrix 微阵列显示，在 Müller 细胞中，TNFα 诱导炎症和增殖相关基因的上调，包括 NFKB2、白血病抑制因子、白细胞介素 6、Janus 激酶 1、Jak2、信号转导和转录激活因子 1、Stat2、丝裂原活化蛋白激酶 7 和 MAP4K4，但下调神经祖细胞基因，包括 Sox9、Ascl1、Wnt2 和 Hes1。阻断 Jak/Stat 和 MAPK 途径可减弱 TNFα 诱导的 Müller 细胞增殖。这些结果表明，TNFα 可能驱动小鼠 Müller 细胞的增殖和炎症反应，而不是神经再生潜能。
