The Neuroprotective Effect of Salidroside on Murine Retinal Ganglion Cell Apoptosis Induced by N-Methyl-D-Aspartate

Abstract

Objective: To determine the neuroprotective effects of salidroside (Sal) on murine retinal ganglion cell (RGC) apoptosisinduced by N-methyl-D-aspartate (NMDA). Methods: Thirty-six C57BL6J mice were randomized into a blank normal control group, a model control group, and four experimental group (n=6 each). The right eyes of the experimental groups received a 1.5 µl intravitreal injection 0.1, 0.4, 2, or 8 mmol/L Sal (n=6 mice for each dose) 48 hours before NMDA was injected, and phosphate-buffered saline (PBS, 1.5 µl) were injected intravitreally in the model control group 48 hours before NMDA was injected. Intravitreal NMDA injections (1.5 µl at 0.1 mmol/L), were then performed in the model control group and in the experimental groups. PBS (1.5 µl) was injected intravitreally in the blank control group. Retinas derived from the mice were flatmounted and stained with hematoxylin and eosin to identify the RGCs. The number of RGCs was compared between NMDA and PBS-injected eyes for all groups. The levels of caspase-3 and caspase-8 were analyzed by Western Blot. Data were analyzed using ANOVA. Results: Compared with the blank model group, NMDA induced a significant increase of RGC apoptosis in the model control group and in the experimental groups. Compared with the model control group, Sal significantly inhibited RGC apoptosis in a dose-dependent manner (F=212.0, P<0.001), and the protein expression of caspase-3 and caspase-8 was significantly down regulated (F=168.3, P<0.001). Conclusions: Sal inhibited NMDA-induced RGC apoptosis and provided some neuroprotective effect for glutamate-mediated RGC excitotoxicity. Key words: salidroside; glutamate excitotoxicity; retinal ganglion cells; apoptosis; neuroprotection