CD200Fc Attenuates Retinal Glial Responses and RGCs Apoptosis After Optic Nerve Crush by Modulating CD200/CD200R1 Interaction
CD200Fc Attenuates Retinal Glial Responses and RGCs Apoptosis After Optic Nerve Crush by Modulating CD200/CD200R1 Interaction
复制标题
CD200Fc 通过调节 CD200/CD200R1 相互作用来减弱视神经挤压后视网膜神经胶质反应和 RGC 凋亡
DOI：
10.1007/s12031-017-1020-z
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发表时间：
2018-02-01
影响因子：
3.1
通讯作者：
Xu, Fan
中科院分区：
文献类型：
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作者：
Huang, Rong;Lan, Qianqian;Xu, Fan
探讨具有抗炎作用的CD200R1激动剂CD200Fc对视神经损伤后视网膜胶质细胞过度活化和视网膜神经节细胞（RGCs）凋亡的抑制作用。视神经压迫（ONC）后立即给予CD200Fc一次玻璃体内注射。大鼠于ONC后5天实施安乐死。Brn3a视网膜平载免疫染色法计数RGCs密度。TUNEL法、离子钙结合适配分子1(iba1)（小胶质细胞标志物）和胶质原纤维酸性蛋白（GFAP）（星形胶质细胞和Muller细胞标志物）的免疫印迹分析、环氧化酶-2 （COX-2）、诱导型一氧化氮合酶（iNOS）、单核细胞趋化蛋白1（MCP-1）、肿瘤坏死因子- α (tnf - α)、白细胞介素(IL)-8和IL-10的RT-PCR分析、ELISA检测炎症因子蛋白水平，western blot检测CD200和CD200R1。CD200Fc处理通过抑制RGCs凋亡抑制onc诱导的RGCs丢失。此外，ONC后，CD200Fc处理动物的胶质细胞活化标志物GFAP和iba1的表达以及促炎细胞因子（COX-2、iNOS、MCP-1、tnf - α、IL-8）的产生均降低。同时，CD200Fc处理后，onc诱导大鼠视网膜的抗炎细胞因子IL-10升高。最后，我们发现CD200Fc显著抑制了ONC诱导的CD200表达的增加，并提高了ONC后大鼠视网膜中本已较高的CD200R1基础表达。我们的研究结果表明，CD200Fc在ONC大鼠模型中的抗炎作用是通过CD200和CD200R1的相互作用抑制视网膜胶质细胞的激活，CD200Fc对RGCs的神经保护作用可能抑制其凋亡。
To explore the hypothesis that CD200Fc, a CD200R1 agonist with anti-inflammatory properties, will inhibit retinal glial cells hyperactivation and retinal ganglion cells (RGCs) apoptosis after optic nerve injury. CD200Fc was immediately administered after optic nerve crush (ONC) once by intravitreal injection. Rats were euthanized at 5 days after ONC. The density of RGCs was counted by immunostaining of retina flat mounts for Brn3a. TUNEL assay, immunoblotting analysis of ionized calcium-binding adapter molecule 1(iba1) (microglia marker) and glial fibrillary acidic protein (GFAP) (astrocytes and Muller cells marker), RT-PCR analysis of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), monocyte chemotactic protein 1 (MCP-1), tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-8 and IL-10, ELISA measure protein levels of inflammatory cytokines and western blot analysis of CD200 and CD200R1 were evaluated. CD200Fc treatment suppressed ONC-induced RGCs loss through inhibition of RGCs apoptosis. Additionally, expression of glial cells activation markers GFAP and iba1 and production of pro-inflammatory cytokines (COX-2, iNOS, MCP-1, TNF-alpha, IL-8) were decreased in CD200Fc treated animals after ONC. Meanwhile, anti-inflammatory cytokine IL-10 was increased by CD200Fc treatment in ONC-induced rat retina. Finally, we found that CD200Fc significantly inhibited ONC-induced increased in expression of CD200 and raised the already high basal CD200R1 expression in the rat retina after ONC. Our results demonstrated that the anti-inflammatory effects of CD200Fc in ONC rats model through inhibited the activation of retinal glial cells via the interaction between CD200 and CD200R1, and the neuroprotective effects of CD200Fc on RGCs thought inhibited its apoptosis.