{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T12:54:10Z","timestamp":1789736050980,"version":"4.0.1"},"reference-count":57,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T00:00:00Z","timestamp":1750896000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Diabetes Invest"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Mesenchymal stromal\/stem cells have neuroprotective effects that limit damage to the retina, which is predominantly mediated by the released extracellular vesicles (EVs). This study aims to investigate the protective effect of adipose\u2010derived mesenchymal stem cell\u2010derived EVs (ADSC\u2010EVs) against pyroptosis of retinal ganglion cells (RGCs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>ADSC\u2010EVs were isolated and then characterized. Mouse primary RGCs exposed to high glucose (HG) were applied for <jats:italic>in vitro<\/jats:italic> experiments. miR\u201026a\u20105p expression in RGCs after ADSC\u2010EV treatment was determined by RT\u2010qPCR. Target relation between miR\u201026a\u20105p and histone deacetylase 4 (HDAC4) was identified by luciferase reporter assay. miR\u201026a\u20105p blockad and HDAC4 ectopic expression experiments were conducted to clarify their functions in the pyroptosis of RGCs. The pyroptosis\u2010associated protein GSDMD\u2010N, inflammatory factors, and cell death were further evaluated by western blot, ELISA, and LDH assays, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Exposure to HG reduced RGC viability and increased cell death, GSDMD\u2010N protein level, and IL\u20101\u03b2 and IL\u201018 levels, indicating pyroptosis induction. However, these HG\u2010caused alterations could be reversed by ADSC\u2010EVs. ADSC\u2010EVs transferred miR\u201026a\u20105p into RGCs where miR\u201026a\u20105p targeted HDAC4 to limit its expression and enhance histone H3 lysine 27 acetylation (H3K27ac) modification at the nuclear factor erythroid 2\u2010related factor 2 (Nrf2) promoter region. This effect contributed to increases in Nrf2 protein level and nuclear translocation. Importantly, decreased H3K27ac modification at the Nrf2 promoter region could partially abrogate the inhibiting effect of ADSC\u2010EVs on HG\u2010induced RGC pyroptosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Overall, our findings reveal the beneficial effects of ADSC\u2010EVs shuttling miR\u201026a\u20105p on HG\u2010induced RGCs and determine a potential mechanism responsible for pyroptosis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jdi.70100","type":"journal-article","created":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T12:39:53Z","timestamp":1750941593000},"page":"1597-1609","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Extracellular vesicles from adipose\u2010derived mesenchymal stem cells prevent high glucose\u2010induced retinal ganglion cell pyroptosis through a <scp>microRNA<\/scp>\u201026a\u20105p\u2010dependent mechanism"],"prefix":"10.1111","volume":"16","author":[{"given":"Lei","family":"Tang","sequence":"first","affiliation":[{"name":"Department of Ophthalmology The First People's Hospital of Changde City (Changde Hospital, Xiangya School of Medicine, Central South University)  Changde Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology The First People's Hospital of Changde City (Changde Hospital, Xiangya School of Medicine, Central South University)  Changde Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9366-5998","authenticated-orcid":false,"given":"Jianping","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology The First People's Hospital of Changde City (Changde Hospital, Xiangya School of Medicine, Central South University)  Changde Hunan 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