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Since irreversible neurodegeneration occurs before diagnosable, early diagnosis and effective neuroprotection are critical for glaucoma management. Small extracellular vesicles (sEVs) are demonstrated to be potential novel biomarkers and therapeutics for a variety of diseases. In this study, it is found that intravitreal injection of circulating plasma\u2010derived sEVs (PDEV) from glaucoma patients ameliorated retinal degeneration in chronic ocular hypertension (COH) mice. Moreover, it is found that PDEV\u2010miR\u201029s are significantly upregulated in glaucoma patients and are associated with visual field defects in progressed glaucoma. Subsequently, in vivo and in vitro experiments are conducted to investigate the possible function of miR\u201029s in RGC pathophysiology. It is showed that the overexpression of miR\u201029b\u20103p effectively prevents RGC degeneration in COH mice and promotes the neuronal differentiation of human induced pluripotent stem cells (hiPSCs). Interestingly, engineered sEVs with sufficient miR\u201029b\u20103p delivery exhibit more effective RGC protection and neuronal differentiation efficiency. Thus, elevated PDEV\u2010miR\u201029s may imply systemic regulation to prevent RGC degeneration in glaucoma patients. This study provides new insights into PDEV\u2010based glaucoma diagnosis and therapeutic strategies for neurodegenerative diseases.<\/jats:p>","DOI":"10.1002\/advs.202309307","type":"journal-article","created":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T15:54:01Z","timestamp":1719330841000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Circulating Small Extracellular Vesicles Involved in Systemic Regulation Respond to RGC Degeneration in Glaucoma"],"prefix":"10.1002","volume":"11","author":[{"given":"Tong","family":"Li","sequence":"first","affiliation":[{"name":"State Key Laboratory of Ophthalmology Optometry and Visual Science Eye Hospital of Wenzhou Medical University  Wenzhou 325027 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen\u2010Meng","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Ophthalmology Optometry and Visual Science Eye 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