Dhingra Anuradha, Vardi Noga
University of Pennsylvania, Dept. of Neuroscience.
Wiley Interdiscip Rev Membr Transp Signal. 2012 Sep;1(5):641-653. doi: 10.1002/wmts.43.
Glutamate, a key neurotransmitter in the vertebrate retina, acts via ionotropic and metabotropic receptors. Retina expresses mRNA for all metabotropic glutamate receptors and proteins for all but mGluR3. Every retinal cell class expresses one or more of these receptors. In general, these receptors are present presynaptically and serve to modulate synaptic transmission. While mGluRs on the photoreceptor terminal act as autoreceptors to titer glutamate levels, those on horizontal cell processes seem to shape the light response. Similarly, autoreceptors on bipolar axon terminals modulate glutamate release and the receptors on amacrine and ganglion cells modulate feedforward signals by modulating K or Ca current to fine tune light responses. Since most of the mGluR sub-types are present in amacrine and ganglion cells that belong to many cell types, the pathways downstream of mGluRs are highly diverse with primarily modulatory effects. An exception to most mGluRs which have modulatory function is mGluR6 because it plays a key role in the feedforward transmission from photoreceptors to ON bipolar cells and is also required for the correct localization of the synaptic proteins in the dendritic tips. In humans, mutations in the gene encoding mGluR6 cause autosomal recessive night blindness. In addition, mGluRs appear to play a trophic role in development and after retinal damage, suggesting potential future therapeutic implications.
谷氨酸是脊椎动物视网膜中的一种关键神经递质，通过离子型和代谢型受体发挥作用。视网膜表达所有代谢型谷氨酸受体的信使核糖核酸，除了代谢型谷氨酸受体3外，还表达所有代谢型谷氨酸受体的蛋白质。每种视网膜细胞类型都表达一种或多种这些受体。一般来说，这些受体存在于突触前，用于调节突触传递。光感受器末端的代谢型谷氨酸受体作为自身受体来调节谷氨酸水平，而水平细胞突起上的代谢型谷氨酸受体似乎塑造了光反应。同样，双极轴突末端的自身受体调节谷氨酸释放，无长突细胞和神经节细胞上的受体通过调节钾离子或钙离子电流来调节前馈信号，从而微调光反应。由于大多数代谢型谷氨酸受体亚型存在于属于多种细胞类型的无长突细胞和神经节细胞中，代谢型谷氨酸受体下游的信号通路高度多样，主要起调节作用。大多数具有调节功能的代谢型谷氨酸受体的一个例外是代谢型谷氨酸受体6，因为它在从光感受器到ON双极细胞的前馈传递中起关键作用，并且也是突触蛋白在树突尖端正确定位所必需的。在人类中，编码代谢型谷氨酸受体6的基因突变会导致常染色体隐性夜盲症。此外，代谢型谷氨酸受体似乎在发育过程中和视网膜损伤后发挥营养作用，这表明其具有潜在的未来治疗意义。
