Systemic Mesenchymal Stem Cell Treatment Mitigates Structural and Functional Retinal Ganglion Cell Degeneration in a Mouse Model of Multiple Sclerosis.

摘要: Purpose The purpose of this study was to determine mesenchymal stem cell (MSC) therapy efficacy on rescuing the visual system in experimental autoimmune encephalomyelitis (EAE) model multiple sclerosis (MS) and provide new mechanistic insights. Methods EAE induced female C57BL6 mice by immunization with myelin oligodendrocyte glycoprotein (MOG)35-55, complete Freund's adjuvant, pertussis toxin. findings were compared sham-immunized mice. Half received intraperitoneally delivered cells (EAE + MSC). Clinical progression monitored according a five-point scoring scheme. Pattern electroretinogram (PERG) retinal nerve fiber layer (RNFL) thickness measured 32 days after induction. Retinas harvested ganglion (RGC) density prepared for RNA-sequencing. Results animals that MSC treatment seven induction showed significantly lower motor-sensory impairment, improvement PERG amplitude, preserved RNFL. Analysis RNA-sequencing data demonstrated statistically significant differences gene expression retina MSC-treated Differentially expressed genes enriched pathways involved endoplasmic reticulum stress, endothelial differentiation, HIF-1 signaling, cholesterol transport group. Conclusions Systemic positively affects RGC function survival Better handling increased Abca1, efflux regulatory protein, paired resolution signaling activation might explain improvements seen treatment. Translational relevance Using mouse MS, we discovered previously unappreciated biochemical associated neuroprotection, which have potential be pharmacologically targeted as regimen.