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Effective Treatment of Optic Neuropathies by Intraocular Delivery of MSC-sEVs through Augmenting the G-CSF-Macrophage Pathway
February 12, 2024

Effective Treatment of Optic Neuropathies by Intraocular Delivery of MSC-sEVs through Augmenting the G-CSF-Macrophage Pathway

Optic neuropathies, characterized by injury of retinal ganglion cell (RGC) axons of the optic nerve, cause incurable blindness worldwide. Mesenchymal stem cell–derived small extracellular vesicles (MSC-sEVs) represent a promising “cell-free” 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 Ly6Clow monocytes/monocyte-derived macrophages (Mo/MΦ). Intravitreal administration of G-CSF, a clinically proven agent for treating neutropenia, or donor Ly6Clow Mo/MΦ markedly improved neurological outcomes in vivo. Together, our data define a unique mechanism of MSC-sEV-induced G-CSF-to-Ly6Clow Mo/MΦ signaling in repairing optic nerve injury and highlight local delivery of MSC-sEVs, G-CSF, and Ly6Clow Mo/MΦ as therapeutic paradigms for the treatment of optic neuropathies.

Author(s): Wei Yia, Ying Xuea, Wenjie Qinga , Yingxue Caoa , Lingli Zhoua, Mingming Xua , Zehui Suna , Yuying Lia , Xiaomei Maia , Le Shia , Chang Hea , Feng Zhanga , Elia J. Duhb , Yihai Caoc, and Xialin Liua.

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Experimental Paper of the Month manager:** Anthony Khawaja

Editorial Board: Humma Shahid, Karl Mercieca, Francisco Goni

Editors in Chief: Francesco Oddone, Manuele Michelessi