The prostanoid EP2 receptor agonist ONO-AE1-259-01 protects against glutamate-induced neurotoxicity in rat retina

Prostaglandin E2 (PGE2) plays an important role in promoting inflammation and neurological disorders. The actions of PGE2 are mediated by four different G-protein-coupled receptors (EP1, EP2, EP3, and EP4). The purpose of this study was to determine whether stimulation of prostanoid EP2 receptors has the potential to prevent the excitotoxic injuries in the retina. For this purpose, we examined the effect of 11,15-O-dimethyl prostaglandin E2 (ONO-AE1-259-01), a selective prostanoid EP2 receptor agonist, on N-methyl-D-aspartate (NMDA)-induced neurotoxicity in the rat retina. ONO-AE1-259-01 (2 or 20 nmol) together with NMDA (200 nmol) was given intravitreally, and histological evaluation was performed at 1 week after the injection. ONO-AE1-259-01 concentration-dependently prevented NMDA-induced cell loss in ganglion cell layer and reduction in thickness of inner plexiform layer. These results indicate that ONO-AE1-259-01 protects the excitotoxic injuries in the rat retina, and that the prostanoid EP2 receptor may be a target for neuroprotective intervention in the retinal diseases associated with glutamate-induced excitotoxicity, such as glaucoma and diabetic retinopathy.