N-METHYL-D-ASPARTATE-INDUCED NEUROTOXICITY IN THE ADULT-RAT RETINA
N-METHYL-D-ASPARTATE-INDUCED NEUROTOXICITY IN THE ADULT-RAT RETINA
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DOI：
10.1017/s0952523800005666
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发表时间：
1992-06-01
影响因子：
1.9
通讯作者：
VANTINI, G
中科院分区：
文献类型：
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作者：
SILIPRANDI, R;CANELLA, R;VANTINI, G
本研究提供的证据表明，成年哺乳动物视网膜对NMDA的兴奋毒性作用高度敏感。特别是，我们研究了单次玻璃体内注射不同剂量的n -甲基- d -天冬氨酸（NMDA） （2-200 nmol）对成年大鼠视网膜的影响。视网膜横切面的形态学评价显示神经节细胞层（GCL）细胞的剂量依赖性损失和内丛状层厚度的减少。远端视网膜层未见明显改变。nsll染色全视网膜的定量分析显示，20 NMDA导致70%的体细胞直径大于8 mu-m的细胞（假定是视网膜神经节细胞）丢失；胞体直径小于8 μ m的细胞损失20%（假定为移位的无毛细胞）。此外，NMDA使视网膜胆碱乙酰转移酶（ChAT）活性呈剂量依赖性降低，表明NMDA也影响胆碱能性无分泌细胞。MK-801是一种非竞争性NMDA拮抗剂，完全阻止了NMDA诱导的GCL细胞损失，并以剂量依赖的方式阻断了NMDA诱导的ChAT活性下降。因此，在这些实验中观察到的NMDA的兴奋毒性作用可能是通过NMDA受体亚型介导的。这种“体内”模型可用于识别拮抗或限制中枢神经系统中NMDA受体过度刺激所导致的有害影响的潜在药物。
The present study provides evidence that the adult mammalian retina is highly sensitive to the excitotoxic action of NMDA. In particular, we have investigated the effects of a single intravitreal injection of different doses of N-methyl-D-aspartate (NMDA) (2-200 nmoles) on the adult rat retina. Morphological evaluation of transverse sections of retinae demonstrated a dose-dependent loss of cells in the ganglion cell layer (GCL) and a reduction in the thickness of the inner plexiform layer. No obvious alterations were noted in the more distal retinal layers. Quantitative analyses of Nissl-stained whole-mounted retinae revealed that administration of 20 nmoles of NMDA resulted in a 70% loss of cells with a soma diameter greater than 8-mu-m (presumed retinal ganglion cells); a 20% loss of cells with a soma diameter smaller than 8-mu-m (presumed displaced amacrine cells) was also observed. In addition, NMDA produced a dose-dependent decrease of retinal choline acetyltransferase (ChAT) activity, suggesting that NMDA affects cholinergic amacrine cells as well. MK-801, a non-competitive NMDA antagonist, completely prevented the NMDA-induced loss of cells in the GCL and blocked, in a dose-dependent manner, the NMDA-induced decrease of ChAT activity. The excitotoxic action of NMDA observed in these experiments is thus likely mediated through the NMDA receptor subtype. This "in vivo" model may be utilized to identify potential drugs that antagonize or limit the deleterious effects consequent to NMDA receptor overstimulation in the central nervous system.