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

Chikako Harada, Takayuki Harada, Barbara S. Slusher, Kazuhiko Yoshida, Hidehiko Matsuda, Keiji Wada

Research output: Contribution to journalArticle

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. 100mg/kg 2-PMPA were given with intraperitoneal injections 30min 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. Copyright (C) 2000 Elsevier Science Ireland Ltd.

Original languageEnglish (US)
Pages (from-to)134-136
Number of pages3
JournalNeuroscience Letters
Volume292
Issue number2
DOIs
StatePublished - Oct 6 2000

Keywords

  • 2-(Phosphonomethyl)pentanedioic acid
  • Glutamate
  • N-acetylated-α-linked-acidic dipeptidase inhibitor
  • N-methyl-D-aspartate receptor
  • Retinal ganglion cells
  • Retinal ischemia

ASJC Scopus subject areas

  • Neuroscience(all)

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