Glutamate excitotoxicity is one of the important pathophysiological culprits in retinal ganglion cells (RGCs) damage after acute optic nerve injury such as traumatic optic neuropathies and glaucoma. It is necessary to elucidate the mechanism of glutamate injury to RGCs in order to find the relevant neuroprotector. In this study, it was observed that the expression of Parkin increased and peaked at 24h after glutamate injury to RGCs. Moreover, upregulating Parkin attenuated glutamate induced apoptosis, mitochondrial dysfunction and oxidative stress. And, it was found that Parkin could exert neuroprotective effects on RGCs by inhibiting nucleotide-binding domain leucine-rich repeat containing family pyrin domain containing 3 (NLRP3) inflammasome. Moreover, the genetic and pharmacological downregulation of NLRP3 improved survival of RGCs against glutamate excitotoxicity. In the end, knockdown of Parkin exacerbated glutamate induced RGCs damage via triggering NLRP3 inflammasome activation. Taken together, these results shed light on the promising molecular targets for the prevention and treatment of acute optic nerve injury.
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