Abstract
neural retina is a highly complex tissue composed of excitatory and inhibitory neurons and glial cells. Glutamate, the main excitatory neurotransmitter, mediates information transfer from photoreceptors, bipolar cells, and ganglion cells, whereas interneurons, mainly amacrine and horizontal cells, use γ-aminobutyric acid (GABA), the main inhibitory neurotransmitter. In this review we place an emphasis on glutamate and GABA transporters as highly regulated molecules that play fundamental roles in neurotransmitter clearance, neurotransmitter release, and oxidative stress. We pharmacologically characterized glutamate transporters in chicken retina cells and identified two glutamate transporters: one Na + -dependent transporter and one Na + - independent transporter. The Na + -dependent uptake system presented characteristics related to the high-affinity x AG - system (EAAT1), and the Na + -independent uptake system presented characteristics related to the x CG - system, which highly contributes to glutamate transport in the retina. Glutamate shares the x CG - system with another amino acid, L-cysteine, suggesting the possible involvement of glutathione. Both transporter proteins are present mainly in Muller glial cells. GABA transporters (GATs) mediate high-affinity GABA uptake from the extracellular space and terminate the synaptic action of GABA in the central nervous system. GABA transporters can be modulated by molecules that act on specific sites to promote transporter phosphorylation and dephosphorylation. In addition to a role in the clearance of GABA, GATs may also release GABA through a reverse transport mechanism. In the chicken retina, a GAT-1 blocker, but not GAT2/3 blocker, was shown to inhibit GABA uptake, suggesting that GABA release from retina cells is mainly mediated by a GAT-1-like transporter. Keywords: neuroretina cells, culture, glutamate transporter, GABA transporter.
Highlights
The neural retina is a highly complex tissue composed of excitatory and inhibitory neurons and glial cells
Glutamate transport deficiencies often appear to be associated with neuropathologies that depend on different centers in the central nervous system (CNS) (Doble, 1999; Obrenovitch, Urenjak, Zilkha, & Jay, 2000)
EAAT5, a carrier expressed on photoreceptors and bipolar cell terminals, has glutamategated Cl- conductance but transports substrates poorly, limiting its potential contribution to glutamate clearance in the retina
Summary
The neural retina is a highly complex tissue composed of excitatory and inhibitory neurons and glial cells. Glutamate and γ-aminobutyric acid (GABA) are generally regarded as excitatory and inhibitory neurotransmitters, respectively. The outer retina is one place where glutamate plays an inhibitory role in a subpopulation of bipolar cells, ON bipolar cells. Glutamate is the main excitatory neurotransmitter in the outer and inner plexiform layers, mediating direct information transfer from photoreceptors, bipolar cells, and ganglion cells, whereas interneurons, mainly amacrine and horizontal cells, use GABA. In this review we emphasize studies of glutamate and GABA transporters as highly regulated molecules that play fundamental roles as sensors of both GABA and glutamate uptake and important roles in neurotransmitter clearance, neurotransmitter release, and oxidative stress
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