Department of Biotechnology and Health Sciences, University of Turin, 10126 Turin, Italy.
Eye Clinic, Department of Surgical Sciences, University of Turin, AOU Città della Salute e della Scienza, Ophtalmic Clinic, 10126 Turin, Italy.
Int J Mol Sci. 2021 May 6;22(9):4930. doi: 10.3390/ijms22094930.
Corneal endothelial dystrophy is a relevant cause of vision loss and corneal transplantation worldwide. In the present study, we analyzed the effect of mesenchymal stem cell (MSC)-derived extracellular vesicles (MSC-EVs) in an in vitro model of corneal dystrophy, characterized by endoplasmic reticulum stress. The effects of MSC-EVs were compared with those of serum-derived EVs, reported to display a pro-angiogenic activity. MSC-EVs were able to induce a significant down-regulation of the large majority of endoplasmic reticulum stress-related genes in human corneal endothelial cells after exposure to serum deprivation and tunicamycin. In parallel, they upregulated the Akt pathway and limited caspase-3 activation and apoptosis. At variance, the effect of the serum EVs was mainly limited to Akt phosphorylation, with minimal or absent effects on endoplasmic reticulum stress modulation and apoptosis prevention. The effects of MSC-EVs were correlated to the transfer of numerous endoplasmic reticulum (ER)-stress targeting miRNAs to corneal endothelial cells. These data suggest a potential therapeutic effect of MSC-EVs for corneal endothelial endoplasmic reticulum stress, a major player in corneal endothelial dystrophy.
角膜内皮营养不良是全球范围内导致视力丧失和角膜移植的重要原因。在本研究中，我们分析了间充质干细胞（MSC）衍生的细胞外囊泡（MSC-EVs）在以内质网应激为特征的角膜营养不良体外模型中的作用。将 MSC-EVs 的作用与据报道具有促血管生成活性的血清衍生 EVs 的作用进行了比较。MSC-EVs 能够在人角膜内皮细胞暴露于血清剥夺和衣霉素后，显著下调大多数与内质网应激相关的基因。同时，它们还上调了 Akt 通路，并限制了 caspase-3 的激活和凋亡。相比之下，血清 EVs 的作用主要局限于 Akt 磷酸化，对内质网应激调节和预防凋亡的作用最小或不存在。MSC-EVs 的作用与向角膜内皮细胞转移大量内质网（ER）应激靶向 miRNA 相关。这些数据表明，MSC-EVs 对角膜内皮内质网应激具有潜在的治疗作用，内质网应激是角膜内皮营养不良的主要参与者。
