GABA and Glutamate Uptake and Metabolism in Retinal Glial (Müller) Cells

Abstract

Müller cells, the principal glial cells of the retina, support the synaptic activity by the uptake and metabolization of extracellular neurotransmitters. Müller cells express uptake and exchange systems for various neurotransmitters including glutamate and γ-aminobutyric acid (GABA). Müller cells remove the bulk of extracellular glutamate in the inner retina and contribute to the glutamate clearance around photoreceptor terminals. By the uptake of glutamate, Müller cells are involved in the shaping and termination of the synaptic activity, particularly in the inner retina. Reactive Müller cells are neuroprotective, e.g., by the clearance of excess extracellular glutamate, but may also contribute to neuronal degeneration by a malfunctioning or even reversal of glial glutamate transporters, or by a downregulation of the key enzyme, glutamine synthetase. This review summarizes the present knowledge about the role of Müller cells in the clearance and metabolization of extracellular glutamate and GABA. Some major pathways of GABA and glutamate metabolism in Müller cells are described; these pathways are involved in the glutamate-glutamine cycle of the retina, in the defense against oxidative stress via the production of glutathione, and in the production of substrates for the neuronal energy metabolism.

Long-distance mechanism of neurotransmitter recycling mediated by glial network facilitates visual function in Drosophila

“…I n both vertebrates and insects, glial cells clear neurotransmitters from synaptic clefts (1,2), thereby increasing the signalto-noise ratio, enhancing temporal resolution of synaptic transmission, and preventing cross-talk between neighboring neuronal signaling pathways. Once taken into glia, transmitters can be converted into inactive metabolites and sent back to neurons for reuse (3). This glial process of recycling is crucial for neurons to maintain the necessary level of neurotransmitters, such as glutamate and histamine (4,5), for sustained signal transmission.…”

“…Metabolic enzymes in the recycling process of transmitters, such as glutamate, GABA, and histamine, are also identified (3,8,9). However, our knowledge of the trafficking route of inactive transmitter metabolites to neuronal terminals is still lacking.…”

Characterization of a Spontaneously Immortalized Murine Müller Glial Cell Line QMMuC-1

“…5,21 Current responses at À80 mV were measured by subtracting the baseline current from the maximum recorded current response during drug application. The bathing solution comprised 140 mM NaCl, 3 mM KCl, 1.8 mM CaCl 2 , 0.8 mM MgCl 2 , 3 mM BaCl 2 , 10 mM Na-HEPES, and 5 mM glucose at pH 7.4.…”

“…5 They express electrogenic glutamate transporters, such as GLAST, to uptake and transport glutamate into the cytosol and then use GS to metabolize it into glutamine. Both GLAST and GS were detected in QMMuC-1 cells (Figs.…”

“…2,3 They play a critical role in regulating retinal cell metabolism and ion (mainly K þ ) and water homeostasis in the extracellular space. 4 Müller glia continuously uptake and metabolize neurotransmitters, such as glutamate, 5 and thus are important in supporting synaptic activity and preventing excitotoxicity. Müller glia release various neurotrophic factors and contribute to cell survival and axonal growth.…”