Mesenchymal stem cells-derived small extracellular vesicles alleviate diabetic retinopathy by delivering NEDD4

作者：Fengtian Sun, Yuntong Sun, Junyan Zhu, Xiaoling Wang, Cheng Ji, Jiahui Zhang, Shenyuan Chen, Yifan Yu, Wenrong Xu, Hui Qian · 发表于：Stem Cell Research & Therapy · 年份：2022 · DOI：10.1186/s13287-022-02983-0 · 被引用次数：65 · 研究领域：Retinal Diseases and Treatments、Extracellular vesicles in disease、Retinopathy of Prematurity Studies

BACKGROUND: As a leading cause of vision decline and severe blindness in adults, diabetic retinopathy (DR) is characterized by the aggravation of retinal oxidative stress and apoptosis in the early stage. Emerging studies reveal that mesenchymal stem cells-derived small extracellular vesicles (MSC-sEV) treatment represents a promising cell-free approach to alleviate ocular disorders. However, the repairing effects of MSC-sEV in DR remain largely unclear. This study aimed at exploring the role and the underlying mechanism of MSC-sEV in hyperglycemia-induced retinal degeneration. METHODS: In vivo, we used streptozotocin (STZ) to establish diabetic rat model, followed by the intravitreal injection of MSC-sEV to determine the curative effect. The cell viability and antioxidant capacity of retinal pigment epithelium (RPE) cells stimulated with high-glucose (HG) medium after MSC-sEV treatment were analyzed in vitro. By detecting the response of cell signaling pathways in MSC-sEV-treated RPE cells, we explored the functional mechanism of MSC-sEV. Mass spectrometry was performed to reveal the bioactive protein which mediated the role of MSC-sEV. RESULTS: The intravitreal injection of MSC-sEV elicited antioxidant effects and counteracted retinal apoptosis in STZ-induced DR rat model. MSC-sEV treatment also reduced the oxidative level and enhanced the proliferation ability of RPE cells cultured in HG conditions in vitro. Further studies showed that the increased level of phosphatase an...