Optimizing Extracellular Vesicle Therapy for Retinal Ganglion Cell Protection Following Optic Nerve Injury
Leila Satarian1 *
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
Abstract: Extracellular vesicles (EVs) derived from various mesenchymal stromal cells (MSCs) show significant potential for protecting retinal ganglion cells (RGCs). However, the effective source of MSC-derived EVs and EV subpopulation for nerve regeneration still need more study.
Methods: The EVs derived from various sources of MSCs including human clonal bone marrow (cBM), dental pulp (DP), and trabecular meshwork (TM). MSC-EVs were isolated through high-speed (20K) and ultracentrifugation (110K) methods. The functionality of the EVs were then assessed in mouse model with optic nerve crush (ONC) injury.
Results: All ultracentrifuged MSC-EVs improved the optomotor response. The TM-EVs exhibited a lower survival rate for Brn3a-positive RGCs. Due to the compliance with GMP standards of clonal MSC-EVs, we proceeded with these EVs. Retrograde tracing of RGCs and visual behavior indicated that both 20K and 110K subpopulations of cBM-EVs were effective. Anti-apoptotic indicators, the p-AKT/AKT and p-PI3K/PI3K ratios were upregulated after cBM-EV-20K in the retina and optic nerve. Furthermore, procaspase and caspase levels, the apoptotic markers were reduced in EV-treated animals.
Conclusion: Increased restoration of visual behavior and the levels of p-AKT/AKT and p-PI3K/PI3K ratios through cBM-EV-20K may be responsible for the degenerating RGCs protection afforded by multi-trophic factors within EVs. This could be a significant advancement towards potentially employing cBM-EVs in the healing of injured optic nerves.
