Localization and expression of the glutamate transporter, excitatory amino acid transporter 4, within astrocytes of the rat retina

Ward, Matthew S.; Jobling, Andrew I; Puthussery, Theresa; Foster, Lisa; Fletcher, Erica L.

doi:10.1007/s00441-003-0849-3

Cited by 54 publications

(48 citation statements)

References 24 publications

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“…We have recently shown that EAAT4 is expressed by astrocytes in the retina [14]. Figure 1c and d shows EAAT4 labelling in whole-mounted control and diabetic rat retinae 12 weeks post-diabetogenesis.…”

Section: Glutamate Transporter Expression In Müller Cells and Astrocymentioning

confidence: 87%

“…Astrocytes are intricately linked with the vasculature and have processes within the nerve fibre and ganglion cell layers [12]. The function of astrocytes within the retina is not clearly defined, although they do express glutamate transporters such as GLAST and EAAT4 [13,14]. Highlighting the potential importance of these glutamate transporters in retinal pathology, studies have reported increased glutamate concentrations within the vitreous of patients with diabetes and in diabetic retinae [15,16].…”

Section: Introductionmentioning

confidence: 99%

“…In order to maintain normal retinal function, glutamate must be removed rapidly from the synaptic cleft. At the molecular level, five glutamate transporters have been cloned: excitatory amino acid transporters (EAAT) 1-5, all of which have been identified in the retina [13,14,[18][19][20][21][22]. Although the function of specific transporter types is contentious, it is clear that GLAST (EAAT1) is the predominant transporter for removal of glutamate within the retina and defects in its function lead to major deleterious effects on vision [20,23,24].…”

Section: Introductionmentioning

confidence: 99%

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Glutamate uptake in retinal glial cells during diabetes

et al. 2005

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Aims: Glutamate recycling is a major function of retinal Müller cells. The aim of this study was to evaluate the expression and function of glutamate transporters during diabetes. Methods: Sprague-Dawley rats were rendered diabetic by a single dose of streptozotocin (50 mg/kg). Following 12 weeks of diabetes, immunolocalisation and mRNA expression of the two glial cell transporters, GLAST and EAAT4 were evaluated using indirect immunofluorescence and real-time PCR. The function of glutamate transport was investigated at 1, 4 and 12 weeks following induction of diabetes by measuring the level of uptake of the non-metabolisable glutamate analogue, D-aspartate, into Müller cells. Results: There was no difference in the localisation of either GLAST or EAAT4 during diabetes. Although there was a small apparent increase in expression of both GLAST and EAAT4 in diabetic retinae compared with controls this was not statistically significant. At 1, 4 and 12 weeks following diabetes, D-aspartate immunoreactivity was significantly increased in Müller cells of diabetic rats compared to controls (p<0.001). The EC 50 was found to increase by 0.304 log units in diabetic Müller cells compared with controls, suggesting that glutamate uptake is twice as efficient. Conclusions: These data suggest that there are alterations in glutamate transport during diabetes. However, these changes are unlikely to play a significant role in glutamate-induced neuronal excitoxicity during diabetes. These results suggest that although Müller cells undergo gliosis at an early stage of diabetes, one of the most important functions for maintaining normal retinal function is preserved within the retina.

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Section: Glutamate Transporter Expression In Müller Cells and Astrocymentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Glutamate uptake in retinal glial cells during diabetes

et al. 2005

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“…The mammalian retina expresses all the excitatory amino acid transporters, GLAST, GLT-1, EAAC1, EAAT4, and EAAT 5 (Seal and Amara, 1998;Pow, 2001a;Ward et al, 2004). Although it is known the transporters are expressed by different retinal cell types (Pow, 2001a), the relative contribution of the The primer design and PCR conditions were as described by Matsuo et al (2002).…”

Section: Discussionmentioning

confidence: 99%

“…EAAC1 (EAAT3) is present in neurons in the inner retina (Rauen et al, 1996;Schultz and Stell, 1996). EAAT4 has been reported in retinal astrocytes (Ward et al, 2004), while EAAT5 is localized to photoreceptors, bipolar cells, and possibly some Mü ller cells (Arriza et al, 1997;Eliasof et al, 1998a;Barnett and Pow, 2000).…”

Section: Introductionmentioning

confidence: 99%

Glutamate transport by retinal Müller cells in glutamate/aspartate transporter‐knockout mice

Sarthy

Pignataro

Pannicke

et al. 2004

Glia

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Glutamate transporters are involved in maintaining extracellular glutamate at a low level to ensure a high signal-to-noise ratio for glutamatergic neurotransmission and to protect neurons from excitotoxic damage. The mammalian retina is known to express the excitatory amino acid transporters, EAAT1-5; however, their specific role in glutamate homeostasis is poorly understood. To examine the role of the glial glutamate/ aspartate transporter (GLAST) in the retina, we have studied glutamate transport by Mü ller cells in GLAST Ϫ/Ϫ mice, using biochemical, electrophysiological, and immunocytochemical techniques. Glutamate uptake assays indicated that the K m value for glutamate uptake was similar in wild-type and GLAST Ϫ/Ϫ mouse retinas, but the V max was ϳ50% lower in the mutant. In Na ϩ -free medium, the V max was further reduced by 40%. In patch-clamp recordings of dissociated Mü ller cells from GLAST Ϫ/Ϫ mice, application of 0.1 mM glutamate evoked no current showing that the cells lacked functional electrogenic glutamate transporters. The result also indicated that there was no compensatory upregulation of EAATs in Mü ller cells. [ 3 H]D-Aspartate uptake autoradiography, however, showed that Na ϩ -dependent, high-affinity transporters account for most of the glutamate uptake by Mü ller cells, and that Na ϩ -independent glutamate transport is negligible. Additional experiments showed that the residual glutamate uptake in Mü ller cells in the GLAST Ϫ/Ϫ mouse retina is not due to known glutamate transporters-cystine-glutamate exchanger, ASCT-1, AGT-1, or other heteroexchangers. The present study shows that while several known glutamate transporters are expressed by mammalian Mü ller cells, new Na ϩ -dependent, high-affinity glutamate transporters remain to be identified.

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High‐affinity Na⁺/K⁺‐dependent glutamate transporter EAAT4 is expressed throughout the rat fore‐ and midbrain

Massie

Cnops

Smolders

et al. 2008

J of Comparative Neurology

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Excitatory amino acid transporter 4 (EAAT4), a member of the high-affinity Na+/K+-dependent glutamate transporter family, is highly enriched in Purkinje cells of the cerebellum, although it is not restricted to these cells. The detailed expression of EAAT4 protein in different adult rat fore- and midbrain regions was examined. Despite moderate expression levels compared with the cerebellum, EAAT4 protein was omnipresent throughout the fore- and midbrain. With antibodies raised against the N-terminal mouse EAAT4 sequence, the highest protein expression levels were observed in the substantia nigra pars compacta, ventral tegmental area, paranigral nucleus, habenulo-interpeduncular system, supraoptic nucleus, lateral posterior thalamic nucleus, subiculum, and superficial layers of the superior colliculus. Relatively high levels of EAAT4 protein were also detected in the hippocampal principal cells, in the glutamatergic, gamma-aminobutyric acid (GABA)ergic, dopaminergic and most likely cholinergic cells of all nuclei of the basal ganglia, and in neurons of layers II/III and V of the cerebral cortex. The expression of EAAT4 was confirmed at the mRNA level in some important fore- and midbrain structures by in situ hybridization and reverse transcriptase-polymerase chain reaction (RT-PCR) and estimated to range from 6.7 to 1.6% of the amount in the cerebellum as measured by real-time PCR.

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Localization and expression of the glutamate transporter, excitatory amino acid transporter 4, within astrocytes of the rat retina

Cited by 54 publications

References 24 publications

Glutamate uptake in retinal glial cells during diabetes

Glutamate uptake in retinal glial cells during diabetes

Glutamate transport by retinal Müller cells in glutamate/aspartate transporter‐knockout mice

High‐affinity Na⁺/K⁺‐dependent glutamate transporter EAAT4 is expressed throughout the rat fore‐ and midbrain

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Localization and expression of the glutamate transporter, excitatory amino acid transporter 4, within astrocytes of the rat retina

Cited by 54 publications

References 24 publications

Glutamate uptake in retinal glial cells during diabetes

Glutamate uptake in retinal glial cells during diabetes

Glutamate transport by retinal Müller cells in glutamate/aspartate transporter‐knockout mice

High‐affinity Na+/K+‐dependent glutamate transporter EAAT4 is expressed throughout the rat fore‐ and midbrain

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High‐affinity Na⁺/K⁺‐dependent glutamate transporter EAAT4 is expressed throughout the rat fore‐ and midbrain