Increased Müller cell density during diabetes is ameliorated by aminoguanidine and ramipril

Lo, Tim; Klunder, Luke; Fletcher, Erica L.

doi:10.1111/j.1444-0938.2001.tb05038.x

Cited by 10 publications

(9 citation statements)

References 26 publications

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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%

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%

Glutamate uptake in retinal glial cells during diabetes

et al. 2005

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“…The major changes exhibited by glial cells include hypertrophy, enlargement of the soma and proliferation, although the nature of the glial response depends on the type of injury or disease. Müller cells in both animal models of diabetes and patients display an increase in expression of the intermediate filament, glial fibrillary acidic protein (GFAP) [85][86][87][88][89][90]. In animal models of diabetes, an increase in GFAP labelling within Müller cells and an increase in Müller cell density have been reported from 12 weeks of diabetes [85,[87][88][89][90].…”

Section: Glial Cell Changes During Diabetes: Gliosismentioning

confidence: 99%

Neuronal and Glial Cell Abnormality as Predictors of Progression of Diabetic Retinopathy

Fletcher¹,

Phipps²,

Ward³

et al. 2007

CPD

179

138

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Diabetes is known to cause significant alterations in the retinal vasculature. Indeed, diabetic retinopathy is the leading cause of blindness in those of working age. Considerable evidence is emerging that indicates that retinal neurons are also altered during diabetes. Moreover, many types of neuronal deficits have been observed in animal models and patients prior to the onset of vascular compromise. Such clinical tools as the flash ERG, multifocal ERG, colour vision, contrast sensitivity and short-wavelength automated perimetry, all provide novel means whereby neuronal dysfunction can be detected at early stages of diabetes. The underlying mechanisms that lead to neuronal deficits are likely to be broad. Retinal glial cells play an essential role in maintaining the normal function of the retina. There is accumulating evidence that Müller cells are abnormal during diabetes. They are known to become gliotic, display altered potassium siphoning, glutamate and GABA uptake and are also known to express several modulators of angiogenesis. This review will examine the evidence that neurons and glia are altered during diabetes and the relationship these changes have with vascular compromise.

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“…Downregulation of the glutamine synthetase results in a depletion of neuronal glutamate (Gionfriddo et al, 2009). No alterations, or even a slight enhancement, in the glutamine synthetase expression in Müller cells was observed in diabetic retinopathy and after optic nerve crush (Mizutani et al, 1998; Lo et al, 2001; Chen and Weber, 2002; Gerhardinger et al, 2005; but, see Yu et al, 2009). An increase in the glutamine synthetase expression was also observed under conditions of increased ammonia (Germer et al, 1997; see below).…”

Section: Glutamate Uptake and Metabolismmentioning

confidence: 99%

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

Bringmann¹,

Grosche²,

Pannicke³

et al. 2013

Front. Endocrinol.

144

123

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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.

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Increased Müller cell density during diabetes is ameliorated by aminoguanidine and ramipril

Cited by 10 publications

References 26 publications

Glutamate uptake in retinal glial cells during diabetes

Glutamate uptake in retinal glial cells during diabetes

Neuronal and Glial Cell Abnormality as Predictors of Progression of Diabetic Retinopathy

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

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