Traumatic optic neuropathy results in the loss of retinal ganglion cells (RGCs), leading to unavoidable visual impairment. However, there is no effective therapy by far. Accumulated studies support the perception that mesenchymal stem cells (MSCs) secrete exosomes that serve as a protective paracrine factor. The study aimed to explore and evaluate the potential therapeutic effects of intravitreal transplantation of MSC-derived exosomes (MSC-exos) in an experimental model of optic nerve crush (ONC). Exosomes were isolated from rat MSCs and characterized by transmission electron microscope and western blotting. At the onset of ONC, a single intravitreal injection of exosomes or PBS was administered to the rats. At day 30, hematoxylin and eosin staining, immunohistochemistry, and βIII-tubulin staining were performed to evaluate the survival of RGCs. Moreover, TUNEL assay was used to examine the apoptosis of RGCs. Inflammation-relevant factors were identified via quantitative polymerase chain reaction. The expression levels of cell apoptosis-related molecules and key members of the PI3K/AKT signaling pathway were determined via western blot analysis. We found that MSC-exos exhibited typical characteristic morphologies (cup-shaped) and sizes (peak size of 93 nm). Furthermore, they exhibited substantial expression of the exosome markers CD63 and TSG101, but lacked the expression of the cellular marker GM130. Treatment with intravitreal MSC-exos notably promoted the survival of RGCs in ONC rats. The level of pro-inflammatory cytokines, including TNF-α, IL-1β, IL-6, IL-8, and MCP-1, were reduced, whereas those of the anti-inflammatory factor IL-10 were increased. Moreover, the apoptosis induced by ONC was decreased by the administration of MSC-exos via upregulation of the Bcl-2/Bax ratio and downregulation of caspase-3 activity. Furthermore, MSC-exos significantly stimulated AKT phosphorylation, whereas LY294002 restored the apoptosis-preventing effects of MSC-exos. The results of our results demonstrated that intravitreal administration of MSC-exos ameliorates ONC-induced injury in a rat model. These findings might aid in the development of effective exosome-based therapeutic strategies for the treatment of optic nerve degeneration.

创伤性视神经病变会导致视网膜神经节细胞 (RGC) 的丧失，从而导致不可避免的视力障碍。但是，目前还没有有效的治疗方法。累积的研究支持间充质干细胞 (MSC) 分泌外泌体作为保护性旁分泌因子的看法。该研究旨在探索和评估玻璃体内移植 MSC 衍生的外泌体 (MSC-exos) 在视神经挤压 (ONC) 实验模型中的潜在治疗效果。从大鼠 MSC 中分离出外泌体，并通过透射电子显微镜和蛋白质印迹进行表征。在 ONC 开始时，给大鼠单次玻璃体内注射外泌体或 PBS。在第 30 天，进行苏木精和伊红染色、免疫组织化学和 βIII-微管蛋白染色以评估 RGC 的存活率。此外，TUNEL 测定用于检查 RGCs 的凋亡。通过定量聚合酶链反应确定炎症相关因素。通过蛋白质印迹分析确定细胞凋亡相关分子和 PI3K/AKT 信号通路关键成员的表达水平。我们发现 MSC-exos 表现出典型的特征形态（杯形）和大小（峰值大小为 93 nm）。此外，它们表现出外泌体标志物 CD63 和 TSG101 的大量表达，但缺乏细胞标志物 GM130 的表达。玻璃体内 MSC-exos 治疗显着促进了 ONC 大鼠中 RGC 的存活。促炎细胞因子，包括 TNF-α、IL-1β、IL-6、IL-8 和 MCP-1 的水平降低，而抗炎因子 IL-10 的水平增加。而且，通过上调 Bcl-2/Bax 比率和下调 caspase-3 活性，MSC-exos 的施用减少了 ONC 诱导的细胞凋亡。此外，MSC-exos 显着刺激 AKT 磷酸化，而 LY294002 恢复了 MSC-exos 的凋亡预防作用。我们的结果表明，玻璃体内施用 MSC-exos 可改善大鼠模型中 ONC 诱导的损伤。这些发现可能有助于开发基于外泌体的治疗视神经变性的有效治疗策略。我们的结果表明，玻璃体内施用 MSC-exos 可改善大鼠模型中 ONC 诱导的损伤。这些发现可能有助于开发基于外泌体的治疗视神经变性的有效治疗策略。我们的结果表明，玻璃体内施用 MSC-exos 可改善大鼠模型中 ONC 诱导的损伤。这些发现可能有助于开发基于外泌体的治疗视神经变性的有效治疗策略。