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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2024,2,6]]},"abstract":"<jats:p>\n                    Optic neuropathies, characterized by injury of retinal ganglion cell (RGC) axons of the optic nerve, cause incurable blindness worldwide. Mesenchymal stem cell\u2013derived small extracellular vesicles (MSC-sEVs) represent a promising \u201ccell-free\u201d therapy for regenerative medicine; however, the therapeutic effect on neural restoration fluctuates, and the underlying mechanism is poorly understood. Here, we illustrated that intraocular administration of MSC-sEVs promoted both RGC survival and axon regeneration in an optic nerve crush mouse model. Mechanistically, MSC-sEVs primarily targeted retinal mural cells to release high levels of colony-stimulating factor 3 (G-CSF) that recruited a neural restorative population of Ly6C\n                    <jats:sup>low<\/jats:sup>\n                    monocytes\/monocyte-derived macrophages (Mo\/M\u03a6). Intravitreal administration of G-CSF, a clinically proven agent for treating neutropenia, or donor Ly6C\n                    <jats:sup>low<\/jats:sup>\n                    Mo\/M\u03a6 markedly improved neurological outcomes in vivo. Together, our data define a unique mechanism of MSC-sEV-induced G-CSF-to-Ly6C\n                    <jats:sup>low<\/jats:sup>\n                    Mo\/M\u03a6 signaling in repairing optic nerve injury and highlight local delivery of MSC-sEVs, G-CSF, and Ly6C\n                    <jats:sup>low<\/jats:sup>\n                    Mo\/M\u03a6 as therapeutic paradigms for the treatment of optic neuropathies.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2305947121","type":"journal-article","created":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T13:30:15Z","timestamp":1706621415000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":14,"title":["Effective treatment of optic neuropathies by intraocular delivery of MSC-sEVs through augmenting the G-CSF-macrophage 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