N-acetylated-alpha-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-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.

• Authors: C Harada, T Harada, B S Slusher, K Yoshida, H Matsuda, K Wada
• Journal: Neuroscience letters (Neurosci Lett) Vol. 292 Issue 2 Pg. 134-6 (Oct 06 2000) ISSN: 0304-3940 [Print] Ireland
• PMID: 10998567 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 2-(phosphonomethyl)pentanedioic acid
• Neuroprotective Agents
• Organophosphorus Compounds
• Carboxypeptidases
• Glutamate Carboxypeptidase II

Topics

• Animals
• Carboxypeptidases (antagonists & inhibitors, metabolism)
• Glutamate Carboxypeptidase II
• Mice
• Mice, Inbred C57BL
• Neuroprotective Agents (pharmacology)
• Optic Neuropathy, Ischemic (drug therapy, metabolism)
• Organophosphorus Compounds (pharmacology)
• Pressure
• Reperfusion Injury (drug therapy, metabolism)
• Retinal Ganglion Cells (enzymology, pathology)