Diabetes Reduces Glutamate Oxidation and Glutamine Synthesis in the Retina

Lieth, Erich; LaNoue, Kathryn F.; Antonetti, David A.; Ratz, Michael

doi:10.1006/exer.2000.0840

Cited by 156 publications

(117 citation statements)

References 28 publications

(32 reference statements)

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“…Furthermore, the level of glutamate within the vitreous of patients with diabetes and in diabetic rat retinae is elevated [15,16]. However, the major enzyme involved in glutamate degradation within Müller cells, glutamine synthetase, is only moderately affected [25,26]. These studies suggest that glutamate transport within the retina during diabetes might be abnormal.…”

Section: Introductionmentioning

confidence: 89%

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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: Introductionmentioning

confidence: 89%

“…Previous studies have suggested that glutamate turnover is likely to be abnormal in diabetes [15,16,25,27]. D-Aspartate is a non-metabolisable substrate for GLAST.…”

Section: Diabetic Müller Cells Have Enhanced D-aspartate Uptakementioning

confidence: 99%

Glutamate uptake in retinal glial cells during diabetes

et al. 2005

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“…Peroxynitrite plays a key role in mediating different aspects of DR. In response to hyperglycemia-induced oxidative stress, both microglial and macroglial cells are activated, and the function of macroglia in transporting glutamate by glutamate transporters and in metabolizing glutamate by GS may be impaired (Li and Puro, 2002;Lieth et al, 1998Lieth et al, , 2000. This may lead to glutamate accumulation, such as that reported in the vitreous humor of diabetic patients (Ambati et al, 1997) To protect the rights of the author(s) and publisher we inform you that this PDF is an uncorrected proof for internal business use only by the author(s), editor(s), reviewer(s), Elsevier and typesetter SPi.…”

Section: P0705mentioning

confidence: 99%

“…Müller glial cells in diabetes showed reduced glutamate aspartate transporter (GLAST) function (Li and Puro, 2002) and impaired glutamine synthesis. The adverse effects of diabetes on the function of Müller cells in transporting glutamate by GLAST or in metabolizing glutamate by glutamine synthase (GS) have been widely studied (Kowluru et al, 2001;Li and Puro, 2002;Lieth et al, 2000). Although alterations in GLAST activity during diabetes remain controversial, impairment of GS activity is convincingly evident (Mysona et al, 2009;Ward et al, 2005;Zeng et al, 2009).…”

mentioning

confidence: 99%

Neuropeptides, Trophic Factors, and Other Substances Providing Morphofunctional and Metabolic Protection in Experimental Models of Diabetic Retinopathy

Szabadfi

Pintér

Reglődi

et al. 2014

International Review of Cell and Molecular Biology

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Any queries or remarks that have arisen during the processing of your manuscript are listed below and are highlighted by flags in the proof. (AU indicates author queries; ED indicates editor queries; and TS/TY indicates typesetter queries.) Please check your proof carefully and answer all AU queries. Mark all corrections and query answers at the appropriate place in the proof (e.g., by using on-screen annotation in the PDF file http:// www.elsevier.com/book-authors/science-and-technology-book-publishing/overviewof-the-publishing-process) or compile them in a separate list, and tick off below to indicate that you have answered the query. Please return your input as instructed by the project manager. Location in ChapterQuery / remark AU:1, page 47 Please check the change made in the table title. AU:2, page 57 Citation " Frank et al. (1997)" has not been found in the reference list. Please supply full details for this reference. AU:3, page 58Citation "Wang et al. (2004)" has not been found in the reference list. Please supply full details for this reference. AU:4, page 63The citation "Wang et al. (2010)" has been changed to " Wang et al. (2010)" to match the author name/date in the reference list. Please check here and in subsequent occurrences, and correct if necessary. AU:5, page 3The abbreviations IBA-1 and ZFDM are used only once in the text and they have been deleted in the text. Please consider deleting them from the abbreviation list. B978-0-12-800179-0.00001-5, 00001 IRCMB, 978-0-12-800179-0To protect the rights of the author(s) and publisher we inform you that this PDF is an uncorrected proof for internal business use only by the author(s), editor(s), reviewer(s), Elsevier and typesetter SPi. It is not allowed to publish this proof online or in print. This proof copy is the copyright property of the publisher and is confidential until formal publication. AU:6, page 3Please check if all occurrences of "interstitial cell adhesion molecule 1" should be changed to "intercellular adhesion molecule 1." AU:7, page 3Please check the change from "neural" to "neuronal" to match with the text.AU:8, page 3The abbreviation "PKCa" is not used in the text. Please check and delete from the abbreviation list. AU:9, page 9Please check if "retinal ganglion cells (RGCs)" is okay as edited.AU:10, page 13 Please check the change from "retinal circuity" to "retinal circuitry."AU:11, page 17 Please check if "polyamine catabolism" is okay as edited. AU:20, page 46 Please check if edit to sentence starting "The STZ-induced diabetic. . ." is okay. B978-0-12-800179-0.00001-5, 00001 IRCMB, 978-0-12-800179-0To protect the rights of the author(s) and publisher we inform you that this PDF is an uncorrected proof for internal business use only by the author(s), editor(s), reviewer(s), Elsevier and typesetter SPi. It is not allowed to publish this proof online or in print. This proof copy is the copyright property of the publisher and is confidential until formal publication. AU:21, page 72Please check if "SST" is okay as edited.AU:2...

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“…Whether diabetes affects vascular or neural retina first, both microglial and macroglial cells are activated [15]. The function of activated macroglia in transporting [16] and metabolizing glutamate may be impaired [16,17]. This leads to glutamate accumulation [18][19][20][21].…”

Section: Diabetic Retinopathymentioning

confidence: 99%

Role of adenosine in diabetic retinopathy

Liou

Ahmad

Naime

et al. 2011

j ocul biol dis inform

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In diabetic retinopathy (DR), abnormalities in vascular and neuronal function are closely related to the local production of inflammatory mediators whose potential source is microglia. Adenosine and its receptors have been shown to possess anti-inflammatory properties that have only recently been studied in DR. Here, we review recent studies that determined the roles of adenosine and its associated proteins, including equilibrative nucleoside transporters, adenosine receptors, and underlying signaling pathways in retinal complications associated with diabetes.

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Diabetes Reduces Glutamate Oxidation and Glutamine Synthesis in the Retina

Cited by 156 publications

References 28 publications

Glutamate uptake in retinal glial cells during diabetes

Glutamate uptake in retinal glial cells during diabetes

Neuropeptides, Trophic Factors, and Other Substances Providing Morphofunctional and Metabolic Protection in Experimental Models of Diabetic Retinopathy

Role of adenosine in diabetic retinopathy

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