Encapsulated mesenchymal stem cell-derived exosomes promote optic nerve regeneration and functional recovery in a mouse model of optic nerve crush injury.

AIMS: Optic nerve injury (ONI) is a major cause of irreversible blindness, and current treatments have limited success. This study investigated the therapeutic potential of encapsulated exosomes derived from mesenchymal stem cells (MSC-exosomes) in a mouse model of optic nerve crush (ONC) injury, with the hypothesis that encapsulation would enhance exosome stability and efficacy, promoting optic nerve regeneration and functional recovery.

MATERIALS AND

METHODS

Exosomes derived from human umbilical cord MSCs were isolated and characterized, then encapsulated within a biocompatible hydrogel. Mice subjected to ONC injury received one of the following treatments: hydrogel alone (ONC + HG), exosomes alone (ONC + EXO), or encapsulated exosomes (ONC+ enEXO). Visual evoked potentials (VEPs) were assessed at 21 days post-injury (dpi). Gene expression of regeneration-associated markers (Sox2, Pax6, Brn3, NG2, NF200), retinal ganglion cell (RGC) survival, and axonal regeneration were evaluated using real-time PCR, immunofluorescence, retrograde tracing, and histological analysis.

KEY FINDINGS: Encapsulated exosomes significantly improved VEP parameters, increased the expression of key regeneration-associated genes, and promoted RGC survival and axonal regeneration compared to ONC, ONC + HG, and ONC + EXO groups.

SIGNIFICANCE: These findings provide strong evidence for the therapeutic potential of hydrogel-encapsulated MSC-derived exosomes as a promising treatment for ONC.

CHEMICAL COMPOUNDS: Hydrogel, Exosome, NF200, Sox2, Pax6, Brn3, NG2, MSC secretome, RGC trophic factors.