scholarly journals Effects of inhibiting glutamine synthetase and blocking glutamate uptake on b-wave generation in the isolated rat retina

1999 ◽  
Vol 16 (2) ◽  
pp. 345-353 ◽  
Author(s):  
BARRY S. WINKLER ◽  
NATALIA KAPOUSTA-BRUNEAU ◽  
MATTHEW J. ARNOLD ◽  
DANIEL G. GREEN
Keyword(s):  
Amino Acids ◽  
Glutamine Synthetase ◽  
Glutamate Uptake ◽  
Müller Cells ◽  
Glutamate Transporters ◽  
Methionine Sulfoximine ◽  
Muller Cells ◽  
Rat Retina ◽  
Subsequent Conversion ◽  
Isolated Rat

The purpose of the present experiments was to evaluate the contribution of the glutamate-glutamine cycle in retinal glial (Müller) cells to photoreceptor cell synaptic transmission. Dark-adapted isolated rat retinas were superfused with oxygenated bicarbonate-buffered media. Recordings were made of the b-wave of the electroretinogram as a measure of light-induced photoreceptor to ON-bipolar neuron transmission. L-methionine sulfoximine (1–10 mM) was added to superfusion media to inhibit glutamine synthetase, a Müller cell specific enzyme, by more than 99% within 5–10 min, thereby disrupting the conversion of glutamate to glutamine in the Müller cells. Threo-hydroxyaspartic acid and D-aspartate were used to block glutamate transporters. The amplitude of the b-wave was well maintained for 1–2 h provided 0.25 mM glutamate or 0.25 mM glutamine was included in the media. Without exogenous glutamate or glutamine the amplitude of the b-wave declined by about 70% within 1 h. Inhibition of glutamate transporters led to a rapid (2–5 min) reversible loss of the b-wave in the presence and absence of the amino acids. In contrast, inhibition of glutamine synthetase did not alter significantly either the amplitude of the b-wave in the presence of glutamate or glutamine or the rate of decline of the b-wave found in the absence of these amino acids. Excellent recovery of the b-wave was found when 0.25 mM glutamate was resupplied to L-methionine sulfoximine–treated retinas. The results suggest that in the isolated rat retina uptake of released glutamate into photoreceptors plays a more important role in transmitter recycling than does uptake of glutamate into Müller cells and its subsequent conversion to glutamine.

Reduced glutamate uptake by retinal glial cells under ischemic/hypoxic conditions

1999 ◽  
Vol 16 (1) ◽  
pp. 149-158 ◽  
Author(s):  
GENEVIEVE A. NAPPER ◽  
MICHAEL J. PIANTA ◽  
MICHAEL KALLONIATIS
Keyword(s):  
Glial Cells ◽  
Extracellular Space ◽  
Glutamate Uptake ◽  
Müller Cells ◽  
Uptake System ◽  
Muller Cells ◽  
Rat Retina ◽  
Glutamate Neurotoxicity ◽  
High K ◽  
Isolated Rat

The high-affinity uptake of glutamate by glial cells and neurons of the central nervous system, including the retina, serves to inactivate synaptically released glutamate and maintains glutamate at low concentrations in the extracellular space. This uptake prevents accumulation of glutamate extracellularly and thus minimizes the possibility of glutamate neurotoxicity secondary to ischemic insult. One mechanism whereby glutamate neurotoxicity may occur in ischemic/hypoxic insult is through increased extracellular K+ reversing the electrogenic glutamate uptake into retinal glial (Müller) cells. We investigated glial uptake of the amino acids glutamate, GABA, and D-aspartate in the intact isolated rat retina under high extracellular K+ conditions and under conditions simulating ischemia. Immunocytochemical findings showed that uptake of glutamate and GABA by Müller cells in the intact isolated rat retina continues under conditions simulating ischemia and high extracellular K+ conditions, and uptake of D-aspartate also continues under high K+ conditions. However, under high K+ conditions, the glutamate uptake system saturates at a lower concentration of exogenous glutamate than in the normal K+ condition. These findings provide evidence that disruption of glutamate uptake by Müller cells is likely to be a significant contributing factor to excess glutamate accumulation in the extracellular space which can lead to neurotoxicity.

Neurochemical changes following postmortem ischemia in the rat retina

1999 ◽  
Vol 16 (6) ◽  
pp. 1169-1180 ◽  
Author(s):  
GENEVIEVE A. NAPPER ◽  
MICHAEL KALLONIATIS
Keyword(s):  
Amino Acids ◽  
Müller Cells ◽  
Müller Cell ◽  
Degradation Pathways ◽  
Muller Cells ◽  
Cell Loading ◽  
Rat Retina ◽  
Glutamate Production ◽  
Muller Cell

Glutamate and γ-aminobutyric acid (GABA) are the dominant amino acids in the retina and brain. The manufacturing and degradation pathways of both of these amino acids are intricately linked with the tricarboxylic acid cycle leading to rapid redistribution of these amino acids after metabolic insult. Postmortem ischemia in mammalian retina predominantly results in a loss of glutamate and GABA from neurons and accumulation of these amino acids within Müller cells. This accumulation of glutamate and GABA in Müller cells may occur as a result of increased release of these neurotransmitters from neurons, and decreased degradation. Quantification of the semisaturation value (half-maximal response) for glutamate and GABA Müller cell loading during postmortem ischemia indicated a shorter semisaturation value for GABA than glutamate. Such changes are consistent with a single aerobically dependent GABA-degradation pathway, and the existence of multiple glutamate-degradation pathways. Comparison with the in vitro ischemic model showed similar qualitative characteristics, but a markedly increased semisaturation time for glutamate and GABA Müller cell loading (a factor of 5–10) in the postmortem ischemia model. We interpret these differences to indicate that the in vitro condition provides a more immediate and/or severe ischemic insult. In the postmortem ischemia model, the delayed glial cell loading implies the availability of internal stores of both glucose and/or oxygen. Increased glial and neuronal immunoreactivity for the amino acids involved in transamination reactions, aspartate, alanine, leucine, and ornithine was observed, indicating a potential shift in the equilibrium of transamination reactions associated with glutamate production. These findings provide evidence that, in the rat retina, there are multiple pathways subserving glutamate production/degradation that include a multitude of transamination reactions. Further evidence is therefore provided to support a role for all four amino acids in glutamate metabolism within a variety of retinal neurons and glia.

Developmental expression of dysbindin in Muller cells of rat retina

2013 ◽  
Vol 116 ◽  
pp. 1-8 ◽  
Author(s):  
Andrea Matteucci ◽  
Lucia Gaddini ◽  
Gianfranco Macchia ◽  
Monica Varano ◽  
Tamara C. Petrucci ◽  
...  
Keyword(s):  
Müller Cells ◽  
Developmental Expression ◽  
Muller Cells ◽  
Rat Retina

Expression of brain/kidney protein in Müller cells of rat retina following transient ischemia

2000 ◽  
Vol 293 (1) ◽  
pp. 53-56 ◽  
Author(s):  
Won-Kyu Ju ◽  
Sung-Ho Choi ◽  
Jae-Sung Kwon ◽  
Oh-Joo Kwon ◽  
Mun-Yong Lee ◽  
...  
Keyword(s):  
Müller Cells ◽  
Muller Cells ◽  
Transient Ischemia ◽  
Rat Retina

scholarly journals Abnormalities in Glutamate Metabolism and Excitotoxicity in the Retinal Diseases

Scientifica ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Makoto Ishikawa
Keyword(s):  
Glutamine Synthetase ◽  
Physiological Condition ◽  
Glutamate Uptake ◽  
Glutamate Transporters ◽  
Retinal Diseases ◽  
Glutamate Metabolism ◽  
Retinal Neurons ◽  
Major Pathway ◽  
Excitatory Neurotransmitter ◽  
Pathological Conditions

In the physiological condition, glutamate acts as an excitatory neurotransmitter in the retina. However, excessive glutamate can be toxic to retinal neurons by overstimulation of the glutamate receptors. Glutamate excess is primarily attributed to perturbation in the homeostasis of the glutamate metabolism. Major pathway of glutamate metabolism consists of glutamate uptake by glutamate transporters followed by enzymatic conversion of glutamate to nontoxic glutamine by glutamine synthetase. Glutamate metabolism requires energy supply, and the energy loss inhibits the functions of both glutamate transporters and glutamine synthetase. In this review, we describe the present knowledge concerning the retinal glutamate metabolism under the physiological and pathological conditions.

Effects of taurine on glutamate uptake and degradation in Müller cells under diabetic conditions via antioxidant mechanism

2010 ◽  
Vol 45 (2) ◽  
pp. 192-199 ◽  
Author(s):  
Kaihong Zeng ◽  
Hongxia Xu ◽  
Ka Chen ◽  
Jundong Zhu ◽  
Yong Zhou ◽  
...  
Keyword(s):  
Glutamate Uptake ◽  
Müller Cells ◽  
Muller Cells ◽  
Antioxidant Mechanism
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