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 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-alpha-linked-acidic dipeptidase) inhibitor, an enzyme responsible for the hydrolysis of the neuropeptide NAAG (N-acetyl-aspartyl-glutamate) to N-acetyl-aspartate and glutamate. 100mg/kg 2-PMPA were given with intraperitoneal injections 30 min before ischemia followed per hour injection for 3h. 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.
Harada
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C
Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan. harada@ncnp.go.jp
Harada
T
T
Slusher
B S
BS
Yoshida
K
K
Matsuda
H
H
Wada
K
K
D000818:Animals; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D043425:Glutamate Carboxypeptidase II; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018917:Optic Neuropathy, Ischemic / Q000188:drug therapy* / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D011312:Pressure; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism; D012165:Retinal Ganglion Cells / Q000201:enzymology* / Q000473:pathology*
C402107:2-(phosphonomethyl)pentanedioic acid; D018696:Neuroprotective Agents; D009943:Organophosphorus Compounds; D002268:Carboxypeptidases; D043425:Glutamate Carboxypeptidase II