Therapeutic effects of mesenchymal stem cell-derived exosomes on retinal detachment
Therapeutic effects of mesenchymal stem cell-derived exosomes on retinal detachment
复制标题
间充质干细胞来源的外泌体对视网膜脱离的治疗作用
DOI：
10.1016/j.exer.2019.107899
复制
发表时间：
2020-02-01
影响因子：
3.4
通讯作者：
Zhang, Xiaomin
中科院分区：
文献类型：
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作者：
Ma, Mingming;Li, Bing;Zhang, Xiaomin
视网膜脱离导致视网膜缺血和缺氧，导致多种病理事件，光感受器细胞变性和死亡是导致视力下降的最终原因。在这项研究中，我们研究了间充质干细胞衍生的外切体(MSC-Exos)对大鼠视网膜脱离(RD)模型的治疗作用。采用雄性SD大鼠视网膜下注射1%透明质酸的方法建立模型。在视网膜分离时视网膜下注射MSC-Exos以研究其治疗作用。RT-PCR检测视网膜炎性细胞因子TNF-α、IL-1β和MCP-1的表达水平，Western印迹法检测视网膜自噬相关蛋白5(ATG5)和微管相关蛋白1轻链3β(LC3)的表达，TUNEL法检测视网膜细胞凋亡。视网膜脱离后7d观察到视网膜结构。采用iTRAQ技术结合一维纳米LC-Nano-ESI-MS/MS对MSC-Exos携带的蛋白质进行蛋白质组学分析，发现经MSC-Exo处理后，肿瘤坏死因子-α和IL-1β的表达显著减少，Lc3-II/Lc3-I比值增加，ATG5的裂解减少。与对照组相比，MSC-Exos治疗还抑制了光感受器细胞的凋亡，并维持了正常的视网膜结构。蛋白质组学分析表明，MSC-Exos含有抗炎、神经保护和抗细胞凋亡的蛋白质。这些结果表明，MSC-Exos对RD诱导的视网膜损伤有治疗作用，可用于减轻视网膜脱离对患者感光细胞变性的影响。
Retinal detachment (RD) induces ischemia and oxygen deficiency in the retina and results in multiple pathological events; photoreceptor cell degeneration and death is the eventual cause of vision decline. In this study, we investigated the therapeutic effects of mesenchymal stem cell-derived exosomes (MSC-Exos) in a rat retinal detachment (RD) model. The model was developed using a subretinal injection of 1% hyaluronic acid in male Sprague-Dawley rats. MSC-Exos were sub-retinally injected at the time of retinal separation to study their therapeutic function. The retinal expression levels of inflammatory cytokines TNF-alpha, IL-1 beta, and MCP-1 were detected by RT-PCR, the autophagy-related protein 5 (Atg5) and microtubule-associated protein 1 light chain 3 beta (LC3) were detected by Western blot, and apoptosis was examined using TUNEL assays at 3 days following RD. Retinal structure was observed at 7 days post-RD. Proteomic analysis was also performed to detect proteins carried by MSC-Exos using iTRAQ-based technology combined with one-dimensional nano LC-nano-ESI-MS/MS. We found that expression of TNF-alpha and IL-1 beta were significantly reduced, the LC3-II to LC3-I ratio was enhanced and cleavage of Atg5 was decreased after MSC-Exo treatment. Treatment with MSC-Exos also suppressed photoreceptor cell apoptosis and maintained normal retinal structure when compared to control groups. Proteomic analysis revealed that MSC-Exos contained proteins with anti-inflammatory, neuroprotective and anti-apoptotic effects. These results suggest that MSC-Exos have therapeutic effects on RD-induced retinal injury and can be used to reduce effects of retinal detachment on photoreceptor cell degeneration in patients.