Kalloniatis M, Tomisich G
Department of Optometry and Vision Sciences, University of Melbourne, Parkville, Australia.
Prog Retin Eye Res. 1999 Nov;18(6):811-66. doi: 10.1016/s1350-9462(98)00036-6.
The dominant neurochemicals involved in encoding sensory information are the amino acid neurotransmitters, glutamate, gamma-aminobutyrate (GABA) and glycine, which mediate fast point-to-point synaptic transmission in the retina and other parts of the central nervous system. The relative abundance of these neurochemicals and the existence of neuronal and glial uptake mechanisms as well as a plethora of receptors support the key role these neurochemicals play in shaping neural information. However, in addition to subserving neurotransmitter roles, amino acids subserve normal metabolic,cellular functions, may be precursors for other amino acids, and may also be associated with protein synthesis. Post-embedding immunocytochemistry of small molecules has allowed the characterization of multiple amino acid profiles within subpopulations of neurons in the vertebrate retina. The general theme emerging from these studies is that the retinal through pathway uses glutamate as its neurotransmitter, and the lateral elements, GABA and/or glycine. Co-localization studies using quantitative immunocytochemistry have shown that virtually all neuronal space can be accounted for by the three dominant amino acids. In addition, co-localization studies have demonstrated that there are no purely aspartate, glutamine, alanine. leucine or ornithine immunoreactive neurons and thus these amino acids are likely to act as metabolites and may sustain glutamate production through a multitude of enzymatic pathways. The mapping of multiple cellular metabolic profiles during development or in degenerating retinas has shown that amino acid neurochemistry is a sensitive marker for metabolic activity. In the degenerating retina, (RCS retina), neurochemical anomalies were evident early in development (from birth), even before photoreceptors mature at PND6-8 implying a generalized metabolic dysfunction. Identification of metabolic anomalies within subpopulation of neurons is now possible and can be used to investigate a multitude of retinal functions including amino acid metabolic and neurochemical changes secondary to external insult as well as to expand our understanding of the intricate interrelationship between neurons and glia.
参与编码感觉信息的主要神经化学物质是氨基酸神经递质，即谷氨酸、γ-氨基丁酸（GABA）和甘氨酸，它们介导视网膜及中枢神经系统其他部位的快速点对点突触传递。这些神经化学物质的相对丰度、神经元和胶质细胞摄取机制的存在以及大量受体支持了这些神经化学物质在塑造神经信息方面所起的关键作用。然而，除了发挥神经递质作用外，氨基酸还具有正常的代谢和细胞功能，可能是其他氨基酸的前体，也可能与蛋白质合成有关。小分子的包埋后免疫细胞化学已能够对脊椎动物视网膜中神经元亚群内的多种氨基酸谱进行表征。这些研究得出的总体结论是，视网膜的直通通路以谷氨酸作为神经递质，而侧向成分则以GABA和/或甘氨酸作为神经递质。使用定量免疫细胞化学的共定位研究表明，实际上所有神经元空间都可由这三种主要氨基酸来解释。此外，共定位研究表明不存在纯粹的天冬氨酸、谷氨酰胺、丙氨酸。亮氨酸或鸟氨酸免疫反应性神经元，因此这些氨基酸可能作为代谢产物发挥作用，并可能通过多种酶促途径维持谷氨酸的产生。对发育过程中或退化视网膜中多种细胞代谢谱的绘制表明，氨基酸神经化学是代谢活动的敏感标志物。在退化的视网膜（RCS视网膜）中，神经化学异常在发育早期（从出生起）就很明显，甚至在出生后第6 - 8天光感受器成熟之前，这意味着存在普遍的代谢功能障碍。现在可以识别神经元亚群内的代谢异常，并可用于研究多种视网膜功能，包括外部损伤继发的氨基酸代谢和神经化学变化，以及扩展我们对神经元与胶质细胞之间复杂相互关系的理解。
