Exosomes derived from microRNA-22-3p-overexpressed mesenchymal stem cells protect retinal ganglion cells by regulating MAPK pathway

Abstract Glaucoma is the leading cause of irreversible blindness and is characterized by progressive retinal ganglion cell (RGC) loss and retinal nerve fiber layer thinning. Currently, no existing treatment is effective for the preservation of RGCs. MicroRNA-22-3p (miR22) and exosomes derived from mesenchymal stem cells (MSC-Exos) have neuroprotective effects. In this study, we applied miR22-overexpressing MSC-Exos in an N-methyl-D-aspartic acid (NMDA)-induced RGC injury model to assess their therapeutic effects and explore the underlying mechanisms. We found that mice in the miR22-Exos-treated group had thicker retinas, fewer apoptotic cells, more reserved RGCs, better retinal function, and lower expression levels of caspase-3. MiR22-Exos treatment promoted proliferation, and inhibited apoptosis and caspase-3 expression in RGC-5 cells. MiR22 targeted mitogen-activated protein kinase kinase kinase 12 to inhibit apoptosis by regulating the mitogen-activated protein kinase (MAPK) signaling pathway. Collectively, our results suggest that miR22-Exos ameliorate NMDA-induced RGC injury through the inhibition of MAPK signaling pathway-mediated apoptosis, providing a potential therapy for glaucoma and other diseases that involve RGC damage.