Polydatin's neuroprotective mechanism in optic nerve injury: targeting mitochondrial function and glial cell activation

Optic nerve injury (ONI) frequently causes irreversible visual impairment, making it a significant clinical challenge. This study evaluated the neuroprotective effects of polydatin (PD), focusing on its ability to preserve mitochondrial function and inhibit glial cell activation. We utilized an in vitro retina-ON explant culture model and a mouse ON crush (ONC) model. PD was administered to assess its impact on mitochondrial protection, apoptosis of retinal ganglion cells (RGCs), glial cell activation, and glial inflammatory responses. Western blot and immunofluorescence analysis were employed to examine the p38 MAPK signaling pathway. A primary retinal progenitor cells (RPCs) oxygen-glucose deprivation/reoxygenation (OGD/R) model was established to evaluate the direct protective effect of PD on retinal neuronal mitochondria. PD treatment significantly preserved mitochondrial numbers, reduced glial cell activation and inflammation, and decreased apoptosis of RGCs in the explant culture model. Western blot and immunofluorescence analysis confirmed the inhibition of the p38 MAPK signaling pathway, which is essential for glial cell activation. In the primary RPCs OGD/R model, PD enhanced cell viability, decreased apoptosis, and preserved mitochondrial integrity, demonstrating its direct protective effect on retinal neuronal mitochondria. These findings were further validated in the mouse ONC model, where PD reduced RGC loss, inflammation, and apoptosis. PD exhibits neuroprotective properties in models of retinal and ONI, likely through its dual mechanism of preserving mitochondrial function and inhibiting glial cell activation. These results support the potential therapeutic use of PD in treating conditions that lead to ON damage and RGC degeneration.