N-acetylated-α-linked-acidic dipeptidase inhibitor has a neuroprotective effect on mouse retinal ganglion cells after pressure-induced ischemia

Abstract Excessive glutamate receptor activation is thought to be involved in the retinal ganglion cell (RGC) death after ischemic injury. In this study, we examined the effect of 2-PMPA (2-(phosphonomethyl)pentanedioic acid) on RGC survival in an ischemia-reperfusion model using C57BL/6 mouse eyes. 2-PMPA is a NAALADase ( N -acetylated-α-linked-acidic dipeptidase) inhibitor, an enzyme responsible for the hydrolysis of the neuropeptide NAAG ( N -acetyl-aspartyl-glutamate) to N -acetyl-aspartate and glutamate. 100 mg/kg 2-PMPA were given with intraperitoneal injections 30 min before ischemia followed per hour injection for 3 h. 2-PMPA increased surviving RGCs as well as retinal thickness after pressure-induced retinal ischemia. In addition, neuroprotection afforded by 2-PMPA was greater than that of N -methyl- d -aspartate receptor blocker. These data indicate that NAALADase inhibition may be useful in retinal disorders in which excessive amino acid transmission is pathogenic.