A Perspective on the Müller Cell-Neuron Metabolic Partnership in the Inner Retina

Toft‐Kehler, Anne Katrine; Skytt, Dorte M.; Kolko, Miriam

doi:10.1007/s12035-017-0760-7

Cited by 33 publications

(27 citation statements)

References 83 publications

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“…The exact mechanism of how platelets in the bloodstream influence retinal VEGFA expression is unclear. However, Müller glia cells (where most hypoxia-induced VEGFA is expressed in OIR) have close interactions with both vessels and neurons, and they play an important role in the homeostasis of the retina (19). It is therefore possible that an antiangiogenic stimulus released from platelets is communicated through endothelial cells to Müller cells, resulting in downregulation of Vegfa mRNA and VEGFA protein expression.…”

Section: Discussionmentioning

confidence: 99%

Thrombocytopenia is associated with severe retinopathy of prematurity

Cakir¹,

Liegl²,

Hellgren³

et al. 2018

JCI Insight

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Section: Discussionmentioning

confidence: 99%

Thrombocytopenia is associated with severe retinopathy of prematurity

Cakir¹,

Liegl²,

Hellgren³

et al. 2018

JCI Insight

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“…Given that in astrocytes, insulin signaling is required for efficient glucose uptake into the brain [32], it is likely that intracellular glucose availability is reduced in Akimba macroglia. Sustained glucose deprivation has been described to induce a metabolic shift in Müller cells from glycolysis to OXPHOS [33].…”

Section: Maladaptive Metabolic Changes In Akimba Retinamentioning

confidence: 99%

Single-cell transcriptome analysis of the Akimba mouse retina reveals cell-type-specific insights into the pathobiology of diabetic retinopathy

et al. 2020

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Single-cell RNA sequencing characterizes molecular pathways underlying inflammatory, metabolic, oxidative stress-mediated changes in Akimba model of diabetic retinopathy and identifies distinct functional subtypes of inflammatory & macroglial cells @Oxurion @LambrechtsDlab 2 ABSTRACT AIM: Diabetic retinopathy is a common complication of diabetes and a leading cause of visual impairment and blindness. Despite recent advances, our understanding of its pathophysiology remains incomplete. The aim of this study was to provide deeper insight into the complex network of molecular and cellular changes that underlie diabetic retinopathy by systematically mapping the transcriptional changes that occur in the different cellular compartments of the degenerating diabetic mouse retina. METHODS: Single-cell RNA sequencing was performed on retinal tissue from 12-week-old wild-type and Akimba (Ins2 Akita xVEGF +/-) mice, which are known to replicate features of clinical diabetic retinopathy. This resulted into transcriptome data for 9474 retinal cells, which could be annotated to 8 distinct retinal cell types. Using STRING analysis, we studied differentially expressed gene networks in neuronal, glial and immune cell compartments to create a comprehensive view on the pathological changes that occur in the Akimba retina. Using subclustering analysis, we further characterized macroglial and inflammatory cell subpopulations. Prominent findings were confirmed on protein level using immunohistochemistry, Western blotting and ELISA. RESULTS: At 12 weeks, the Akimba retina was found to display degeneration of rod photoreceptors and presence of inflammatory cells, identified by subclustering analysis as monocyte, macrophage and microglial populations. Analysis of differential expressed genes in the rod, cone, bipolar cell and macroglial compartments indicated changes in cell metabolism and ribosomal gene expression, gliosis, activation of immune system pathways and redox and metal ion dyshomeostasis. Experiments on protein level supported a metabolic shift from glycolysis to oxidative phosphorylation (GAPDH), activation of microglia/macrophages (Isolectin-B4), metal ion and oxidative stress response (metallothionein and heme oxygenase-1) and reactive macroglia (GFAP and S100) in the Akimba retina, as compared to wild-type mice. Our single-cell approach also indicates macroglial subpopulations with distinct fibrotic, inflammatory and gliotic profiles. CONCLUSION: Our study identifies molecular pathways underlying inflammatory, metabolic and oxidative stress-mediated changes in the Akimba mouse model of diabetic retinopathy and distinguishes distinct functional subtypes of inflammatory and macroglial cells.

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“…In the rabbit eye, the amount of glycogen, mainly stored in the inner part of the Müller cells [36], changes with the blood supply of the choroid [37]. A recent review highlighted the metabolic partnership of retinal ganglion cells and Müller cells in the vascularized retina [38]. Müller cells do not only provide glucose for the neurons but also establish a lactate shuttle [39].…”

Section: Concentration Difference Of Nutrientsmentioning

confidence: 99%

Species Differences in the Nutrition of Retinal Ganglion Cells among Mammals Frequently Used as Animal Models

May

2019

Cells

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The diffusion rate for proper nutrition of the inner retina depends mainly on four factors which are discussed in this review: 1. The diffusion distance between blood and retinal ganglion cells shows morphological variants in different mammalian species, namely a choroidal nutrition type, a retinal nutrition type, and a mixture of both types. 2. Low oxygen concentration levels in the inner retina force the diffusion of oxygen especially in the choroidal nutrition type. Other nutrients might be supplied by surrounding cells, mainly Müller cells. 3. Diffusion in the eye is influenced by the intraocular pressure, which is vital for the retinal ganglion cells but might also influence their proper function. Again, the nutrition types established might explain the differences in normal intraocular pressure levels among different species. 4. Temperature is a critical feature in the eye which has to be buffered to avoid neuronal damage. The most effective buffer system is the increased blood turnover in the choroid which has to be established in all species.

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A Perspective on the Müller Cell-Neuron Metabolic Partnership in the Inner Retina

Cited by 33 publications

References 83 publications

Thrombocytopenia is associated with severe retinopathy of prematurity

Thrombocytopenia is associated with severe retinopathy of prematurity

Single-cell transcriptome analysis of the Akimba mouse retina reveals cell-type-specific insights into the pathobiology of diabetic retinopathy

Species Differences in the Nutrition of Retinal Ganglion Cells among Mammals Frequently Used as Animal Models

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