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-α, IL-1β, 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-α and IL-1β 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.

中文翻译：

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间充质干细胞来源的外泌体对视网膜脱离的治疗作用。

视网膜脱离（RD）会引起视网膜缺血和缺氧，并导致多种病理事件。感光细胞的变性和死亡是视力下降的最终原因。在这项研究中，我们调查了大鼠视网膜脱离（RD）模型中的间充质干细胞来源的外泌体（MSC-Exos）的治疗效果。该模型是通过在雄性Sprague-Dawley大鼠中视网膜下注射1％透明质酸而开发的。视网膜分离时在视网膜下注射MSC-Exos，以研究其治疗功能。通过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，检测自噬相关蛋白5（Atg5）和微管相关蛋白1轻链3 beta（LC3）通过蛋白质印迹，并且在RD后3天使用TUNEL测定法检查细胞凋亡。在RD后7天观察到视网膜结构。还使用基于iTRAQ的技术结合一维纳米LC-纳米ESI-MS / MS进行了蛋白质组学分析，以检测MSC-Exos携带的蛋白质。我们发现，MSC-Exo处理后，TNF-α和IL-1β的表达显着降低，LC3-II与LC3-I的比例增加，Atg5的切割减少。与对照组相比，用MSC-Exos进行的治疗还抑制了感光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含有具有抗炎，神经保护和抗凋亡作用的蛋白质。