对NMDA或倍他洛尔应用后氨基酸神经化学的定量分析。

Sun Daniel, Kalloniatis Michael

Department of Optometry, University of Auckland, Auckland, New Zealand.

Clin Exp Ophthalmol. 2004 Oct;32(5):505-17. doi: 10.1111/j.1442-9071.2004.00885.x.

BACKGROUND

Alterations in retinal amino acid neurochemistry are an indicator of metabolic function. Glutamate is the primary excitatory amino acid neurotransmitter within the retina, and excessive levels of glutamate can potentially cause excitotoxicity, in particular, through the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor. Anomalies in NMDA receptor function have been implicated as causing many neurodegenerative disorders, and overactivation leads to neuronal death secondary to metabolic insult. Several pharmaceutical agents have been proposed as potential neuroprotective agents against excitotoxicity (e.g. betaxolol), yet any effects such drugs have on retinal neurochemistry have not been determined. Therefore, the aim of this study was to quantify the changes in retinal amino acid neurochemistry secondary to the application of NMDA with and without betaxolol.

METHODS

Functional NMDA channel activation was confirmed in both amacrine and ganglion cells by quantifying the entry into these neurones of a channel permeable probe (agmatine: 1-amino-4-guanidobutane [AGB]). By probing serial thin sections with immunoglobulins targeting AGB, glutamate, gamma-aminobutyric acid (GABA) and glycine, it was possible to simultaneously study the neurochemical characteristic as well as the NMDA-evoked AGB responses of different neurochemical populations of inner retinal neurones.

RESULTS

The authors have previously shown no accumulation of glutamate or GABA within Muller cells following NMDA application. Herein they report altered GABA and glycine immunoreactivity, but not glutamate immunoreactivity within neurones of the amacrine and ganglion cell layers following NMDA application. Finally, the addition of betaxolol did not significantly alter the normal neurochemistry of the retina.

CONCLUSION

The retina possesses intrinsic mechanisms that allow it to maintain metabolic integrity during short periods of high NMDA application.

背景

视网膜氨基酸神经化学变化是代谢功能的一个指标。谷氨酸是视网膜内主要的兴奋性氨基酸神经递质，过量的谷氨酸可能会导致兴奋性毒性，尤其是通过谷氨酸受体的N-甲基-D-天冬氨酸（NMDA）亚型。NMDA受体功能异常被认为会导致许多神经退行性疾病，过度激活会导致继发于代谢损伤的神经元死亡。几种药物已被提议作为对抗兴奋性毒性的潜在神经保护剂（如倍他洛尔），但此类药物对视网膜神经化学的任何影响尚未确定。因此，本研究的目的是量化在使用和不使用倍他洛尔的情况下，NMDA应用后视网膜氨基酸神经化学的变化。

方法

通过量化通道可渗透探针（胍丁胺：1-氨基-4-胍基丁烷[AGB]）进入无长突细胞和神经节细胞的量，证实了功能性NMDA通道在这两种细胞中的激活。通过用靶向AGB、谷氨酸、γ-氨基丁酸（GABA）和甘氨酸的免疫球蛋白探测连续的薄切片，可以同时研究视网膜内层不同神经化学群体的神经化学特征以及NMDA诱发的AGB反应。