Neuroprotection by rat Müller glia against high glucose-induced neurodegeneration through a mechanism involving ERK1/2 activation

Matteucci, Andrea; Gaddini, Lucia; Villa, Marika; Varano, Monica; Parravano, Mariacristina; Monteleone, Valentina; Cavallo, Francesca; Leo, Lanfranco; Mallozzi, Cinzia; Malchiodi-Albedi, Fiorella; Pricci, Flavia

doi:10.1016/j.exer.2014.05.011

Cited by 45 publications

(45 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…At least nine types of astrocytes with different morphological characteristics have been described in the normal brain. Moreover, morphologically undistinguishable astrocytes can exhibit different physiological behaviour (Matyash and Kettenmann, 2010). The existence of different astrocyte populations is reinforced by the finding that astrocyte reactivity takes place in selected areas of the glaucomatous retina, these "microdomains" possibly serving as biomarkers and predictors of RGC health (Formichella et al, 2014).…”

Section: Astrocyte Heterogeneitymentioning

confidence: 94%

“…It has also been proposed that in early phases of diabetic retinopathy, Müller glial activation does not contribute to neurodegeneration but that it may provoke neuroprotection 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 against high glucose induced neurotoxicity through a mechanism involving phosphorylation of extracellular signal-regulated kinase 1/2, pERK1/2: (Matteucci et al, 2014). Since in vitro high glucose stimulation of Müller cells increases VEGF secretion, the specific ERK1/2 inhibitor, U0126, blocked ERK1/2 phosphorylation and thus, impaired the Müller cells secretion of VEGF that is implicated in the development of diabetic retinopathy (Ye et al, 2010).…”

Section: Glia and Retinal Pathologiesmentioning

confidence: 98%

“…Circulating low-density lipoproteins (LDL) enter the retina via LDL receptors on RPE and Müller cells (Tserentsoodol et al, 2006). There is a lipid shuttle from Müller cells to neurons to meet the need of neurons for lipids, especially to maintain the long RGC axons and the photoreceptor outer segments, as well as for synapse formation (Mauch et al, 2001). Müller cells and astrocytes synthesize ApoE and ApoJ which are assembled into cholesterolrich lipoprotein particles that are thought to be secreted into the vitreous humour.…”

Section: Lipid Metabolismmentioning

confidence: 99%

See 2 more Smart Citations

Glia–neuron interactions in the mammalian retina

Vecino

Rodríguez

Ruzafa

et al. 2016

Progress in Retinal and Eye Research

638

533

View full text Add to dashboard Cite

The mammalian retina provides an excellent opportunity to study glia-neuron interactions and the interactions of glia with blood vessels. Three main types of glial cells are found in the mammalian retina that serve to maintain retinal homeostasis: astrocytes, Müller cells and resident microglia. Müller cells, astrocytes and microglia not only provide structural support but they are also involved in metabolism, the phagocytosis of neuronal debris, the release of certain transmitters and trophic factors and K(+) uptake. Astrocytes are mostly located in the nerve fibre layer and they accompany the blood vessels in the inner nuclear layer. Indeed, like Müller cells, astrocytic processes cover the blood vessels forming the retinal blood barrier and they fulfil a significant role in ion homeostasis. Among other activities, microglia can be stimulated to fulfil a macrophage function, as well as to interact with other glial cells and neurons by secreting growth factors. This review summarizes the main functional relationships between retinal glial cells and neurons, presenting a general picture of the retina recently modified based on experimental observations. The preferential involvement of the distinct glia cells in terms of the activity in the retina is discussed, for example, while Müller cells may serve as progenitors of retinal neurons, astrocytes and microglia are responsible for synaptic pruning. Since different types of glia participate together in certain activities in the retina, it is imperative to explore the order of redundancy and to explore the heterogeneity among these cells. Recent studies revealed the association of glia cell heterogeneity with specific functions. Finally, the neuroprotective effects of glia on photoreceptors and ganglion cells under normal and adverse conditions will also be explored.

show abstract

Section: Astrocyte Heterogeneitymentioning

confidence: 94%

Section: Glia and Retinal Pathologiesmentioning

confidence: 98%

Section: Lipid Metabolismmentioning

confidence: 99%

See 1 more Smart Citation

Glia–neuron interactions in the mammalian retina

Vecino

Rodríguez

Ruzafa

et al. 2016

Progress in Retinal and Eye Research

638

533

View full text Add to dashboard Cite

show abstract

“…Finally, recent studies also stress the importance of neural and glial dysfunction in the pathophysiologic progress of hyperglycemiainduced retinopathy and neurodegeneration as well as glial modifications also occur in the STZ diabetic rodent model [67,68]. Fibrosis is an important pathological feature of early-stage (capillary basement membrane thickening) and late-stage (fibrosis-induced contraction and retinal detachment) DR.…”

Section: Diabetic Modelsmentioning

confidence: 99%

“…Depending on the injection dosage, the onset of diabetes can be achieved within a few days after injection for rats and mice become hyperglycemic in 1 to 4 weeks after STZ injection. Compared to mice, rats are more susceptible to the toxicity of STZ; therefore, usually a much lower dosage of STZ is used [ [64][65][66], neural dysfunction [67,68] and vascular dysfunction [51, [69][70][71][72][73][74][75][76][77] can be studied in this chemically-induced diabetes animal model.…”

Section: Diabetic Modelsmentioning

confidence: 99%

Selection Strategy of In Vivo Models for Ophthalmic Drug Development in Diabetic Retinopathy

Geert¹,

Tjing-Tjing²

2016

J Mol Genet Med

View full text Add to dashboard Cite

Diabetic Retinopathy (DR) is the most common microvascular complication of diabetes and is one of the leading causes of visual impairment worldwide. DR is a chronic eye disease that eventually can result in legal blindness due to the evolution towards the major vision-threatening disorders diabetic macular edema (DME) and/or proliferative diabetic retinopathy (PDR). Current treatments with steroids, anti-VEGF compounds or retinal laser photocoagulation have shown a significant improvement in visual acuity in the advanced stage of the disease. However, main concerns are possible side effects and/or the relatively large number of clinical non-responders. A better understanding of the biological and molecular pathways not only in DR patients but also in the preclinical in vivo models would aid the development of novel and more efficient (personalized) therapeutic approaches for DR. This review aims to describe the pathways in a selection of diabetic, non-diabetic and surrogate rodent models of pathogenic neovascularization, vascular permeability, inflammation and neurodegeneration. None of these models can mimic the entire human pathophysiological progression but they all exhibit joint pathophysiological features with human DR pathogenesis. These combined features make these models very relevant in gaining a better understanding of the disease etiology and eventually improved strategies for drug screening. Through highlighting the most important biochemical and molecular pathways that these animal models have in common with DR patients, selection of the most suitable model for mechanistic studies and drug screening can be facilitated.

show abstract