Nuclear GAPDH: changing the fate of Müller cells in diabetes

Jayaguru, Prathiba; Mohr, Susanne

doi:10.1007/s12177-012-9085-y

Cited by 13 publications

(9 citation statements)

References 71 publications

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“…In some studies, no cell death was observed after 72 h [ 30 ] or after 5 days in HG [ 90 ], while others detected Müller cell apoptosis after 72 h in the same conditions, possibly related to AKT inhibition [ 33 ]. In favor of an apoptotic mechanism is the observation that in rMC-1 and in cultured human primary Müller cells incubated in HG conditions, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) translocates to the nucleus [ 91 ]. A similar nuclear accumulation of GAPDH in Müller cells was observed in retinal sections from diabetic rats at 4 months of diabetes [ 91 ].…”

Section: Müller Glia Involvement In Drmentioning

confidence: 99%

“…In favor of an apoptotic mechanism is the observation that in rMC-1 and in cultured human primary Müller cells incubated in HG conditions, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) translocates to the nucleus [ 91 ]. A similar nuclear accumulation of GAPDH in Müller cells was observed in retinal sections from diabetic rats at 4 months of diabetes [ 91 ].…”

Section: Müller Glia Involvement In Drmentioning

confidence: 99%

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Primary Retinal Cultures as a Tool for Modeling Diabetic Retinopathy: An Overview

Matteucci

Varano

Mallozzi

et al. 2015

BioMed Research International

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Experimental models of diabetic retinopathy (DR) have had a crucial role in the comprehension of the pathophysiology of the disease and the identification of new therapeutic strategies. Most of these studies have been conducted in vivo, in animal models. However, a significant contribution has also been provided by studies on retinal cultures, especially regarding the effects of the potentially toxic components of the diabetic milieu on retinal cell homeostasis, the characterization of the mechanisms on the basis of retinal damage, and the identification of potentially protective molecules. In this review, we highlight the contribution given by primary retinal cultures to the study of DR, focusing on early neuroglial impairment. We also speculate on possible themes into which studies based on retinal cell cultures could provide deeper insight.

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Section: Müller Glia Involvement In Drmentioning

confidence: 99%

Section: Müller Glia Involvement In Drmentioning

confidence: 99%

Primary Retinal Cultures as a Tool for Modeling Diabetic Retinopathy: An Overview

Matteucci

Varano

Mallozzi

et al. 2015

BioMed Research International

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“…Therefore, it is considered that the microtubule encoding protein of human islet tissue TUBA1C might be related with the insulin secretion [25]. Another gene GAPDH , connected with a differentially methyalted gene, although the DNA methylation level of this gene was not aberrant, researches have shown that, this gene could change the etinal Müller cells fate in diabetes[26], and Müiler cells are the most important retinal glial cells of vertebrate[27]. It is shown that H3K4me3 was negatively correlated with DNA methylation.…”

Section: Resultsmentioning

confidence: 99%

Weighted Interaction SNP Hub (WISH) network method for building genetic networks for complex diseases and traits using whole genome genotype data

Kogelman

Kadarmideen

2014

BMC Syst Biol

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BackgroundHigh-throughput genotype (HTG) data has been used primarily in genome-wide association (GWA) studies; however, GWA results explain only a limited part of the complete genetic variation of traits. In systems genetics, network approaches have been shown to be able to identify pathways and their underlying causal genes to unravel the biological and genetic background of complex diseases and traits, e.g., the Weighted Gene Co-expression Network Analysis (WGCNA) method based on microarray gene expression data. The main objective of this study was to develop a scale-free weighted genetic interaction network method using whole genome HTG data in order to detect biologically relevant pathways and potential genetic biomarkers for complex diseases and traits.ResultsWe developed the Weighted Interaction SNP Hub (WISH) network method that uses HTG data to detect genome-wide interactions between single nucleotide polymorphism (SNPs) and its relationship with complex traits. Data dimensionality reduction was achieved by selecting SNPs based on its: 1) degree of genome-wide significance and 2) degree of genetic variation in a population. Network construction was based on pairwise Pearson's correlation between SNP genotypes or the epistatic interaction effect between SNP pairs. To identify modules the Topological Overlap Measure (TOM) was calculated, reflecting the degree of overlap in shared neighbours between SNP pairs. Modules, clusters of highly interconnected SNPs, were defined using a tree-cutting algorithm on the SNP dendrogram created from the dissimilarity TOM (1-TOM). Modules were selected for functional annotation based on their association with the trait of interest, defined by the Genome-wide Module Association Test (GMAT). We successfully tested the established WISH network method using simulated and real SNP interaction data and GWA study results for carcass weight in a pig resource population; this resulted in detecting modules and key functional and biological pathways related to carcass weight.ConclusionsWe developed the WISH network method which is a novel 'systems genetics' approach to study genetic networks underlying complex trait variation. The WISH network method reduces data dimensionality and statistical complexity in associating genotypes with phenotypes in GWA studies and enables researchers to identify biologically relevant pathways and potential genetic biomarkers for any complex trait of interest.

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“…Moreover, hyperglycemia stimulates GAPDH accumulation in the nucleus of retinal Müller cells, in association with the apoptosis of these cells. [ 47 , 50 ]. It is possible that Müller cell death could also affect RGCs, accentuating the deleterious effect of glucose on RGCs.…”

Section: Discussionmentioning

confidence: 99%

Dexamethasone protects retinal ganglion cells but not Müller glia against hyperglycemia in vitro

Pereiro¹,

Ruzafa²,

Acera³

et al. 2018

PLoS ONE

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Diabetic retinopathy (DR) is a common complication of diabetes, for which hyperglycemia is a major etiological factor. It is known that retinal glia (Müller cells) and retinal ganglion cells (RGCs) are affected by diabetes, and there is evidence that DR is associated with neural degeneration. Dexamethasone is a glucocorticoid used to treat many inflammatory and autoimmune conditions, including several eye diseases like DR. Thus, our goal was to study the effect of dexamethasone on the survival of RGCs and Müller glial cells isolated from rat retinas and maintained in vitro under hyperglycemic conditions. The behavior of primary RGC cell cultures, and of mixed RGC and Müller cell co-cultures, was studied in hyperglycemic conditions (30 mM glucose), both in the presence and absence of Dexamethasone (1 μM). RGC and Müller cell survival was evaluated, and the conditioned media of these cultures was collected to quantify the inflammatory cytokines secreted by these cells using a multiplex assay. The role of IL-1β, IL-6 and TNFα in RGC death was also evaluated by adding these cytokines to the co-cultures. RGC survival decreased significantly when these cells were grown in high glucose conditions, reaching 54% survival when they were grown alone and only 33% when co-cultured with Müller glia. The analysis of the cytokines in the conditioned media revealed an increase in IL-1β, IL-6 and TNFα under hyperglycemic conditions, which reverted to the basal concentration in co-cultures maintained in the presence of dexamethasone. Finally, when these cytokines were added to co-cultures they appeared to have a direct effect on RGC survival. Hence, these cytokines could be implicated in the death of RGCs when glucose concentrations increase and dexamethasone might protect RGCs from the cell death induced in these conditions.

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Nuclear GAPDH: changing the fate of Müller cells in diabetes

Cited by 13 publications

References 71 publications

Primary Retinal Cultures as a Tool for Modeling Diabetic Retinopathy: An Overview

Primary Retinal Cultures as a Tool for Modeling Diabetic Retinopathy: An Overview

Weighted Interaction SNP Hub (WISH) network method for building genetic networks for complex diseases and traits using whole genome genotype data

Dexamethasone protects retinal ganglion cells but not Müller glia against hyperglycemia in vitro

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