The Neuroprotective Effect of the Adiponectin Receptor Agonist AdipoRon on Glutamate-Induced Cell Death in Rat Primary Retinal Ganglion Cells

Purpose: To determine whether the adiponectin receptor (AdipoR) agonist AdipoRon inhibits glutamate-induced neuronal cell death and to investigate the neuroprotective mechanism of AdipoRon in rat primary retinal ganglion cells (RGCs). Methods: The expression pattern of AdipoR1 and AdipoR2 in rat retina and primary RGCs was examined by immunostaining. The neuroprotective effect of AdipoRon on glutamate-induced cell death was evaluated in rat primary RGCs. Cellular levels of reactive oxygen species (ROS) were also measured. Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha), estrogen-related receptor-alpha (Esrra), mitochondrial transcription factor A (TFAM), peroxisome proliferator-activated receptor alpha (PPAR alpha), and catalase mRNA levels were examined. Results: The expression of AdipoR1 and AdipoR2 was confirmed in rat retina and primary RGCs. AdipoRon significantly increased the survival rate of glutamate-induced cell death and decreased ROS production. Additionally, the mRNA levels of PGC-1 alpha, Esrra, and TFAM were upregulated by AdipoRon. Conclusions: These results suggest that AdipoRon has a neuroprotective effect by inhibiting ROS production via upregulation of PGC-1 alpha, Esrra, and TFAM against glutamate-induced RGC death.