Adachi K, Kashii S, Masai H, Ueda M, Morizane C, Kaneda K, Kume T, Akaike A, Honda Y
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan.
Graefes Arch Clin Exp Ophthalmol. 1998 Oct;236(10):766-74. doi: 10.1007/s004170050156.
This study was carried out to examine the involvement of glutamate and nitric oxide neurotoxicity in ischemia/reperfusion-induced retinal injury in vivo.
We monitored glutamate release from in vivo cat retina during and after pressure-induced ischemia using a microdialysis technique. Morphometric studies were performed to study the effects of MK-801 (dizocilpine), L-NAME (N omega-nitro-L-arginine methyl ester), and D-NAME (N omega-nitro-D-arginine methyl ester) on the histological changes in the rat retina induced by ischemia or intravitreal injection of NMDA (N-methyl-D-aspartate; 200 nmol).
A large release of glutamate occurred during ischemia, followed by a marked release after reperfusion. Histological changes occurred selectively in the inner part of the retina after ischemia as well as intravitreal injection of NMDA. Pretreatment with intravenous injection of MK-801 or L-NAME significantly inhibited the ischemic injury of the inner retina. Intravitreal injection of L-NAME inhibited NMDA-induced neurotoxicity in the retina.
These findings indicate that nitric oxide mediates neurotoxic actions of glutamate which are responsible for ischemic injury in the retina.
本研究旨在探讨谷氨酸和一氧化氮神经毒性在体内缺血/再灌注诱导的视网膜损伤中的作用。
我们使用微透析技术监测了压力诱导缺血期间及之后猫视网膜在体内的谷氨酸释放情况。进行形态计量学研究，以研究MK-801（地佐环平）、L-NAME（Nω-硝基-L-精氨酸甲酯）和D-NAME（Nω-硝基-D-精氨酸甲酯）对缺血或玻璃体内注射NMDA（N-甲基-D-天冬氨酸；200 nmol）诱导的大鼠视网膜组织学变化的影响。
缺血期间谷氨酸大量释放，再灌注后显著释放。缺血以及玻璃体内注射NMDA后，视网膜内层选择性地出现组织学变化。静脉注射MK-801或L-NAME预处理可显著抑制视网膜内层的缺血损伤。玻璃体内注射L-NAME可抑制NMDA诱导的视网膜神经毒性。
这些发现表明一氧化氮介导了谷氨酸的神经毒性作用，而谷氨酸的神经毒性作用是视网膜缺血损伤的原因。
