Harada C, Harada T, Slusher B S, Yoshida K, Matsuda H, Wada K
Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502, Japan.
Neurosci Lett. 2000 Oct 6;292(2):134-6. doi: 10.1016/s0304-3940(00)01444-0.
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.
过量的谷氨酸受体激活被认为与缺血性损伤后视网膜神经节细胞（RGC）的死亡有关。在本研究中，我们使用C57BL/6小鼠眼睛的缺血再灌注模型，研究了2-磷酸甲基戊二酸（2-PMPA）对RGC存活的影响。2-PMPA是一种N-乙酰化-α-连接酸性二肽酶（NAALADase）抑制剂，该酶负责将神经肽N-乙酰天门冬氨酰谷氨酸（NAAG）水解为N-乙酰天门冬氨酸和谷氨酸。在缺血前30分钟腹腔注射100mg/kg的2-PMPA，随后每小时注射一次，共注射3小时。在压力诱导的视网膜缺血后，2-PMPA增加了存活的RGC数量以及视网膜厚度。此外，2-PMPA提供的神经保护作用大于N-甲基-D-天冬氨酸受体阻滞剂。这些数据表明，抑制NAALADase可能对氨基酸过度传递具有致病性的视网膜疾病有用。
