Ginseng-derived exosomes loaded in fibrin gel promote retinal ganglion cell survival in glaucoma by exerting anti-inflammatory effects through modulating microglial polarization.

Glaucoma is the leading cause of irreversible blindness globally. Chronic neuroinflammation drives progressive retinal ganglion cell (RGC) loss independent of intraocular pressure, yet safe, sustained and precise neuroprotective modulation of the retinal inflammatory microenvironment remains a significant challenge. We developed an injectable fibrin gel delivery system loaded with ginseng-derived exosomes (GE-fibrin gel, GE-gel) to modulate microglial polarization, reduce retinal inflammation and promote RGC survival. In vitro, GE showed strong antioxidant and anti-apoptotic effects by getting rid of reactive oxygen species caused by oxidative stress and lowering apoptosis in R28 cells. Both GE and GE-gel stopped lipopolysaccharide from causing pro-inflammatory M1 polarization of microglia and increased anti-inflammatory M2 phenotypic change. Intravitreal injection of GE-gel suppressed pro-inflammatory microglial activation, diminished neuroinflammation and improved the survival of RGCs in a chronic ocular hypertension rat model. These results show that GE-gel could promote microglial polarization, change the immune environment in the retina and protect RGCs functionally over the long term. This approach may hopefully provide promising solutions for rapid and effective glaucoma therapy.