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Glutamate metabolic pathways and retinal function
Author(s) -
Bui Bang V.,
Hu Rebecca G.,
Acosta Monica L.,
Donaldson Paul,
Vingrys Algis J.,
Kalloniatis Michael
Publication year - 2009
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2009.06354.x
Subject(s) - aminooxyacetic acid , glutamate receptor , biology , biochemistry , glutamine , glutamine synthetase , neurotransmission , glutamic acid , glutamate aspartate transporter , retina , neurotransmitter , amino acid , neuroscience , metabotropic glutamate receptor , enzyme , receptor
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.