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

Excessive glutamate receptor activation is thought to be involved in the re tinal ganglion cell (RGC) death after ischemic injury. In this study, we ex amined the effect of 2-PMPA (2-(phosphonomethyl)pentanedioic acid) on RGC s urvival in an ischemia-reperfusion model using C57BL/6 mouse eyes. 2-PMPA i s a NAALADase (N-acetylated-alpha-linked-acidic dipeptidase) inhibitor, an enzyme responsible for the hydrolysis of the neuropeptide NAAG (N-acetyl-as partyl-glutamate) to N-acetyl-aspartate and glutamate. 100 mg/kg 2-PMPA wer e 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, neuroprote ction afforded by 2-PMPA was greater than that of N-methyl-D-aspartate rece ptor blocker. These data indicate that NAALADase inhibition may be useful i n retinal disorders in which excessive amino acid transmission is pathogeni c. (C) 2000 Elsevier Science ireland Ltd. All rights reserved.