Glutamate metabolic pathways and retinal function
Article first published online: 22 AUG 2009
© 2009 The Authors. Journal Compilation © 2009 International Society for Neurochemistry
Journal of Neurochemistry
Volume 111, Issue 2, pages 589–599, October 2009
How to Cite
Bui, B. V., Hu, R. G., Acosta, M. L., Donaldson, P., Vingrys, A. J. and Kalloniatis, M. (2009), Glutamate metabolic pathways and retinal function. Journal of Neurochemistry, 111: 589–599. doi: 10.1111/j.1471-4159.2009.06354.x
- Issue published online: 23 SEP 2009
- Article first published online: 22 AUG 2009
- Received June 3, 2009; revised manuscript received August 14, 2009; accepted August 14, 2009.
- amino acid;
Glutamate is a major neurotransmitter in the CNS but is also a key metabolite intimately coupled to amino acid production/degradation. We consider the effect of inhibition of two key glutamate metabolic enzymes: glutamine synthetase (GS) and aspartate aminotransferase on retinal function assessed using the electroretinogram to consider photoreceptoral (a-wave) and post-receptoral (b-wave) amplitudes. Quantitative immunocytochemistry was used to assess amino acid levels within photoreceptors, ganglion and Müller cells secondary to GS inhibition. Intravitreal injections of methionine sulfoximine reduced GS immunoreactivity in the rat retina. Additionally, glutamate and its precursor aspartate was reduced in photoreceptors and ganglion cells, but elevated in Müller cells. This reduction in neuronal glutamate was consistent with a deficit in neurotransmission (−75% b-wave reduction). Exogenous glutamine supply completely restored the b-wave, whereas other amino acid substrates (lactate, pyruvate, α-ketoglutarate, and succinate) only partially restored the b-wave (16–20%). Inhibition of the aminotranferases using aminooxyacetic acid had no effect on retinal function. However, aminooxyacetic acid application after methionine sulfoximine further reduced the b-wave (from −75% to −92%). The above data suggest that de novo glutamate synthesis involving aspartate aminotransferase can partially sustain neurotransmission when glutamate recycling is impaired. We also show that altered glutamate homeostasis results in a greater change in amino acid distribution in ganglion cells compared with photoreceptors.