Molecular basis of glutamate toxicity in retinal ganglion cells
Molecular basis of glutamate toxicity in retinal ganglion cells
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DOI：
10.1016/s0042-6989(97)00047-3
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发表时间：
1997-12-01
期刊：
影响因子：
1.8
通讯作者：
Dreyer, EB
中科院分区：
文献类型：
--
作者：
Sucher, NJ;Lipton, SA;Dreyer, EB
视网膜神经节细胞（RGCs）的丧失是许多眼科疾病的标志，包括青光眼、中央动脉闭塞引起的视网膜缺血、前缺血性视神经病变，在视神经炎、视神经创伤和艾滋病中可能很重要。最近的研究表明，神经毒性是由过度刺激兴奋性氨基酸受体引起的。特别是，氨基酸谷氨酸已被证明是一种神经毒素，主要通过谷氨酸受体的n -甲基- d -天冬氨酸（NMDA）亚型对RGCs发挥毒性作用，NMDA受体介导的RGCs毒性依赖于细胞外Ca2+的流入。[Ca2+](i)的增加作为第二个信使，启动导致最终细胞死亡的级联反应。谷氨酸通过与非nmda受体亚型的相互作用刺激其自身释放在一个正反馈回路中，Ca2+诱导的Ca2+释放和谷氨酸诱导的去极化后通过电压门控Ca2+通道进一步流入Df Ca2+有助于谷氨酸毒性。体外和体内研究表明，使用选择性NMDA受体拮抗剂或Ca2+通道阻滞剂应该有助于预防或至少减轻视网膜的正常损失。对于NMDA受体拮抗剂在急性血管损伤治疗中未来临床应用的特别重要的发现是，一些药物可以预防谷氨酸诱导的(C) 1997出版由Elsevier Science Ltd.。
Loss of retinal ganglion cells (RGCs) is a hallmark of many ophthalmic diseases including glaucoma, retinal ischemia due to central artery occlusion, anterior ischemic optic neuropathy and may be significant in optic neuritis, optic nerve trauma, and AIDS. Recent research indicates that neurotoxicity is caused by excessive stimulation of receptors for excitatory amino acids (EAAs). In particular, the amino acid glutamate has been shown to act as a neurotoxin which exerts its toxic effect an RGCs predominantly through the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor, NMDA-receptor-mediated toxicity in RGCs is dependent on the influx of extracellular Ca2+. The increase in [Ca2+](i) acts as a second messenger that sets in motion the cascade leading to eventual cell death. Glutamate stimulates its own release in a positive feedback loop by its interaction with the non-NMDA receptor subtypes, Ca2+-induced Ca2+ release and further influx Df Ca2+ through voltage gated Ca2+ channels after glutamate-induced depolarization contribute to glutamate toxicity. In vitro and in vivo studies suggest that the use of selective NMDA receptor antagonists or Ca2+ channel blockers should be useful in preventing or at least abating normal loss in the retina. Of particular importance for future clinical use of NMDA receptor antagonists in the treatment of acute vascular insults is the finding that some drugs can prevent glutamate-induced (C) 1997 Published by Elsevier Science Ltd.