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Journal ArticleDOI

New functions of Müller cells.

01 May 2013-Glia (Glia)-Vol. 61, Iss: 5, pp 651-678
TL;DR: This review gives a survey of recently discoved new functions of Müller cells, living optical fibers that guide light through the inner retinal tissue that enhance the signal/noise ratio by minimizing intraretinal light scattering and conserve the spatial distribution of light patterns in the propagating image.
Abstract: Muller cells, the major type of glial cells in the retina, are responsible for the homeostatic and metabolic support of retinal neurons. By mediating transcellular ion, water, and bicarbonate transport, Muller cells control the composition of the extracellular space fluid. Muller cells provide trophic and anti-oxidative support of photoreceptors and neurons and regulate the tightness of the blood-retinal barrier. By the uptake of glutamate, Muller cells are more directly involved in the regulation of the synaptic activity in the inner retina. This review gives a survey of recently discoved new functions of Muller cells. Muller cells are living optical fibers that guide light through the inner retinal tissue. Thereby they enhance the signal/noise ratio by minimizing intraretinal light scattering and conserve the spatial distribution of light patterns in the propagating image. Muller cells act as soft, compliant embedding for neurons, protecting them in case of mechanical trauma, and also as soft substrate required for neurite growth and neuronal plasticity. Muller cells release neuroactive signaling molecules which modulate neuronal activity, are implicated in the mediation of neurovascular coupling, and mediate the homeostasis of the extracellular space volume under hypoosmotic conditions which are a characteristic of intense neuronal activity. Under pathological conditions, a subset of Muller cells may differentiate to neural progenitor/stem cells which regenerate lost photoreceptors and neurons. Increasing knowledge of Muller cell function and responses in the normal and diseased retina will have great impact for the development of new therapeutic approaches for retinal diseases.
Citations
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Journal ArticleDOI
TL;DR: 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.

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Abstract: Muller glia in the fish retina respond to injury by reprogramming to a stem-cell-like state that enables them to regenerate all of the major retinal cell types. Goldman reviews our current understanding of the mechanisms that regulate this regenerative response and considers how this knowledge might be applied to improve repair in the mammalian retina.

468 citations

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TL;DR: An overview of the common and distinctive features of retinal neurodegenerative diseases, including the molecular, anatomical and functional changes caused by the cellular response to damage, are provided in order to establish appropriate treatments for these pathologies.

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Cites background from "New functions of Müller cells."

  • ...For more detailed review of these concepts see (Reichenbach and Bringmann, 2013)....

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  • ...The capacity of Müller cells to dedifferentiate to cells with a neuronal phenotype, if it would be confirmed, will represent a promising mechanism for therapeutic interventions since transdifferentiatedMüller cells can be obtained frommany sources, such as immortalized human cell lines or epiretinal membranes surgically removed from the eyes of patients with proliferative retinopathies (Reichenbach and Bringmann, 2013)....

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  • ...For more detailed explanations see (Bringmann et al., 2006; Reichenbach and Bringmann, 2013)....

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  • ...…a promising mechanism for therapeutic interventions since transdifferentiatedMüller cells can be obtained frommany sources, such as immortalized human cell lines or epiretinal membranes surgically removed from the eyes of patients with proliferative retinopathies (Reichenbach and Bringmann, 2013)....

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References
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Book
10 Mar 2010
TL;DR: A proper understanding of the gliotic responses of Müller cells in the diseased retina, and of their protective vs. detrimental effects, is essential for the development of efficient therapeutic strategies that use and stimulate the neuron-supportive/protective-and prevent the destructive-mechanisms of gliosis.
Abstract: Muller glial cells span the entire thickness of the tissue, and ensheath all retinal neurons, in vertebrate retinae of all species. This morphological relationship is reflected by a multitude of functional interactions between neurons and Muller cells, including a 'metabolic symbiosis' and the processing of visual information. Muller cells are also responsible for the maintenance of the homeostasis of the retinal extracellular milieu (ions, water, neurotransmitter molecules, and pH). In vascularized retinae, Muller cells may also be involved in the control of angiogenesis, and the regulation of retinal blood flow. Virtually every disease of the retina is associated with a reactive Muller cell gliosis which, on the one hand, supports the survival of retinal neurons but, on the other hand, may accelerate the progress of neuronal degeneration: Muller cells protect neurons via a release of neurotrophic factors, the uptake and degradation of the excitotoxin, glutamate, and the secretion of the antioxidant, glutathione. However, gliotic Muller cells display a dysregulation of various neuron-supportive functions. This contributes to a disturbance of retinal glutamate metabolism and ion homeostasis, and causes the development of retinal edema and neuronal cell death. Moreover, there are diseases evoking a primary Muller cell insufficiency, such as hepatic retinopathy and certain forms of glaucoma. Any impairment of supportive functions of Muller cells, primary or secondary, must cause and/or aggravate a dysfunction and loss of neurons, by increasing the susceptibility of neurons to stressful stimuli in the diseased retina. On the contrary, Muller cells may be used in the future for novel therapeutic strategies to protect neurons against apoptosis (somatic gene therapy), or to differentiate retinal neurons from Muller/stem cells. Meanwhile, a proper understanding of the gliotic responses of Muller cells in the diseased retina, and of their protective vs. detrimental effects, is essential for the development of efficient therapeutic strategies that use and stimulate the neuron-supportive/protective-and prevent the destructive-mechanisms of gliosis.

1,507 citations


"New functions of Müller cells." refers background in this paper

  • ...1 (Bringmann et al., 2006; Kofuji et al., 2000; Kofuji and Newman, 2004)....

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  • ...A major functional role of Müller cells is the control of osmotic and ionic homeostasis, mediated by transglial ion and water transport (Bringmann et al., 2004, 2006; Kofuji and Newman, 2004; Nagelhus et al., 2004)....

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  • ...Müller cells interact with the neurons of their columns in a kind of symbiotic relationship (Bringmann et al., 2006; Reichenbach and Bringmann, 2010)....

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  • ...Müller cells support the functioning and metabolism of retinal neurons and are active players in normal retinal function as well as in virtually all types of retinal degeneration (Bringmann et al., 2006; Newman and Reichenbach, 1996)....

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  • ...Müller cells interact with the neurons of their columns in a kind of symbiotic relationship (Bringmann et al., 2006; Reichenbach and Bringmann, 2010)....

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Journal ArticleDOI
TL;DR: The aim of this review was to establish a chronology of events leading to and following the publication of the LNDC-REVIEW in 1996.
Abstract: Keywords: Cell Communication Reference LNDC-REVIEW-1996-002View record in PubMed Record created on 2010-01-08, modified on 2017-05-12

1,022 citations


"New functions of Müller cells." refers background in this paper

  • ...They provide trophic substances to neurons, and remove metabolic waste (Tsacopoulos and Magistretti, 1996)....

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Journal ArticleDOI
12 Oct 2006-Nature
TL;DR: It is shown that pericytes can control capillary diameter in whole retina and cerebellar slices and is probably modulators of blood flow in response to changes in neural activity, which may contribute to functional imaging signals and to CNS vascular disease.
Abstract: Neural activity increases local blood flow in the central nervous system (CNS), which is the basis of BOLD (blood oxygen level dependent) and PET (positron emission tomography) functional imaging techniques1, 2, 3. Blood flow is assumed to be regulated by precapillary arterioles, because capillaries lack smooth muscle. However, most (65%) noradrenergic innervation of CNS blood vessels terminates near capillaries rather than arterioles4, and in muscle and brain a dilatory signal propagates from vessels near metabolically active cells to precapillary arterioles5, 6, suggesting that blood flow control is initiated in capillaries. Pericytes, which are apposed to CNS capillaries and contain contractile proteins7, could initiate such signalling. Here we show that pericytes can control capillary diameter in whole retina and cerebellar slices. Electrical stimulation of retinal pericytes evoked a localized capillary constriction, which propagated at approx2 microm s-1 to constrict distant pericytes. Superfused ATP in retina or noradrenaline in cerebellum resulted in constriction of capillaries by pericytes, and glutamate reversed the constriction produced by noradrenaline. Electrical stimulation or puffing GABA (gamma-amino butyric acid) receptor blockers in the inner retina also evoked pericyte constriction. In simulated ischaemia, some pericytes constricted capillaries. Pericytes are probably modulators of blood flow in response to changes in neural activity, which may contribute to functional imaging signals and to CNS vascular disease. Top

1,016 citations


"New functions of Müller cells." refers background in this paper

  • ..., 2009), evoke constriction and relaxation, respectively, of pericytes (Li and Puro, 2001; Peppiatt et al., 2006)....

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  • ...ATP and adenosine, which are released from both neurons and glial cells (Housley et al., 2009), evoke constriction and relaxation, respectively, of pericytes (Li and Puro, 2001; Peppiatt et al., 2006)....

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Journal ArticleDOI
TL;DR: The magnitude of the deforming forces in the optical stretcher bridges the gap between optical tweezers and atomic force microscopy for the study of biologic materials.

959 citations

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TL;DR: The effect of various drugs affecting the integrity of different components of the cytoskeleton on the elasticity of two fibroblast cell lines was investigated by elasticity measurements with an atomic force microscope (AFM).

912 citations