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However, the effects of MSC-sEVs on endothelial dysfunction of DR and the mechanism is still unclear. In this study, MSC-sEVs mitigated retinal blood-retina barrier (BRB) impairment in rats with streptozotocin (STZ)-induced DR by reducing ferroptosis in vivo and in vitro. MSC-sEVs miRNA sequencing analysis revealed that miR-125b-5p may mediate human retina microvascular endothelial cells (HRMECs) ferroptosis and P53 as a downstream target based on dual-luciferase reporter assays. Silencing miR-125b-5p in MSC-sEVs reversed the therapeutic effects of MSC-sEVs on rats with DR and advanced glycation end products (AGEs)-treated HRMECs. Additionally, overexpression of miR-125b-5p could diminish ferroptosis in HRMECs, and this effect could be effectively reversed by overexpressing P53. This study indicated the potential therapeutic effect of MSC-sEVs on vascular endothelial function maintenance and that the delivery of sEVs carrying miR-125b-5p could prevent endothelial cell ferroptosis by inhibiting P53, thereby protecting the BRB.<\/jats:p>","DOI":"10.1093\/stmcls\/sxaf023","type":"journal-article","created":{"date-parts":[[2025,4,18]],"date-time":"2025-04-18T07:06:21Z","timestamp":1744959981000},"source":"Crossref","is-referenced-by-count":13,"title":["MSC-derived exosomal miR-125b-5p suppressed retinal microvascular endothelial cell ferroptosis in diabetic retinopathy"],"prefix":"10.1093","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8515-5375","authenticated-orcid":false,"given":"Jun","family":"Tong","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University , Nanjing, Jiangsu Province 210008 ,","place":["People\u2019s Republic of 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