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Journal of Anatomy Oct 2017Müller cells are the predominant glial cell type in the retina of vertebrates. They play a wide variety of roles in both the developing and the mature retina that have... (Review)
Review
Müller cells are the predominant glial cell type in the retina of vertebrates. They play a wide variety of roles in both the developing and the mature retina that have been widely reported in the literature. However, less attention has been paid to their role in phagocytosis of cell debris under physiological, pathological or experimental conditions. Müller glia have been shown to phagocytose apoptotic cell bodies originated during development of the visual system. They also engulf foreign molecules that are injected into the eye, cone outer segments and injured photoreceptors. Phagocytosis of photoreceptor cell debris in the light-damaged teleost retina is primarily carried out by Müller cells. Once the microglial cells become activated and migrate to the photoreceptor cell layer, the phagocytic activity of Müller cells progressively decreases, suggesting a possible mechanism of communication between Müller cells and neighbouring microglia and photoreceptors. Additionally, it has been shown that phagocytic Müller cells acquire proliferating activity in the damaged teleost retina, suggesting that engulfment of apoptotic photoreceptor debris might stimulate the Müller glia to proliferate during the regenerative response. These findings highlight Müller glia phagocytosis as an underlying mechanism contributing to degeneration and regeneration under pathological conditions.
Topics: Animals; Ependymoglial Cells; Humans; Phagocytosis
PubMed: 28695619
DOI: 10.1111/joa.12653 -
Reviews in Endocrine & Metabolic... Dec 2016The activity of the hypothalamus-pituitary-thyroid axis (HPT) is coordinated by hypophysiotropic thyrotropin releasing hormone (TRH) neurons present in the... (Review)
Review
The activity of the hypothalamus-pituitary-thyroid axis (HPT) is coordinated by hypophysiotropic thyrotropin releasing hormone (TRH) neurons present in the paraventricular nucleus of the hypothalamus. Hypophysiotropic TRH neurons act as energy sensors. TRH controls the synthesis and release of thyrotropin, which activates the synthesis and secretion of thyroid hormones; in target tissues, transporters and deiodinases control their local availability. Thyroid hormones regulate many functions, including energy homeostasis. This review discusses recent evidence that covers several aspects of TRH role in HPT axis regulation. Knowledge about the mechanisms of TRH signaling has steadily increased. New transcription factors engaged in TRH gene expression have been identified, and advances made on how they interact with signaling pathways and define the dynamics of TRH neurons response to acute and/or long-term influences. Albeit yet incomplete, the relationship of TRH neurons activity with positive energy balance has emerged. The importance of tanycytes as a central relay for the feedback control of the axis, as well as for HPT responses to alterations in energy balance, and other stimuli has been reinforced. Finally, some studies have started to shed light on the interference of prenatal and postnatal stress and nutrition on HPT axis programing, which have confirmed the axis susceptibility to early insults.
Topics: Animals; Ependymoglial Cells; Humans; Hypothalamus; Signal Transduction; Thyroid Gland; Thyrotropin-Releasing Hormone
PubMed: 27515033
DOI: 10.1007/s11154-016-9375-y -
Current Opinion in Genetics &... Oct 2020Retinal regeneration efficiency from Müller glia varies tremendously among vertebrate species, being extremely limited in mammals. Efforts towards the identification of... (Review)
Review
Retinal regeneration efficiency from Müller glia varies tremendously among vertebrate species, being extremely limited in mammals. Efforts towards the identification of molecular mechanisms underlying Müller cell proliferative and neurogenic potential should help finding strategies to awake them and ensure regeneration in mammals. We provide here an update on the most recent and original progresses made in the field. These include remarkable discoveries regarding (i) unprecedented cross-species comparison of Müller cell transcriptome using single-cell technologies, (ii) the identification of new strategies to promote both the proliferative and the neurogenic potential of mammalian Müller cells, (iii) the role of the epigenome in regulating Müller glia plasticity, (iv) miRNA-based regulatory mechanisms of Müller cell response to injury, and (v) the influence of inflammatory signals on the regenerative process.
Topics: Animals; Cell Proliferation; Cellular Reprogramming; Ependymoglial Cells; Mammals; Nerve Regeneration; Neuroglia; Retina; Wound Healing
PubMed: 32619816
DOI: 10.1016/j.gde.2020.05.025 -
Experimental Cell Research Jun 2024Diabetic retinopathy (DR) is a common microvascular complication that causes visual impairment or loss. Aquaporin 4 (AQP4) is a regulatory protein involved in water...
Diabetic retinopathy (DR) is a common microvascular complication that causes visual impairment or loss. Aquaporin 4 (AQP4) is a regulatory protein involved in water transport and metabolism. In previous studies, we found that AQP4 is related to hypoxia injury in Muller cells. Transient receptor potential cation channel subfamily V member 4 (TRPV4) is a non-selective cation channel protein involved in the regulation of a variety of ophthalmic diseases. However, the effects of AQP4 and TRPV4 on ferroptosis and oxidative stress in high glucose (HG)-treated Muller cells are unclear. In this study, we investigated the functions of AQP4 and TRPV4 in DR. HG was used to treat mouse Muller cells. Reverse transcription quantitative polymerase chain reaction was used to measure AQP4 mRNA expression. Western blotting was used to detect the protein levels of AQP4, PTGS2, GPX4, and TRPV4. Cell count kit-8, flow cytometry, 5,5',6,6'-tetrachloro-1,1,3,3'-tetraethylbenzimidazolyl carbocyanine iodide staining, and glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) kits were used to evaluate the function of the Muller cells. Streptozotocin was used to induce DR in rats. Haematoxylin and eosin staining was performed to stain the retina of rats. GSH, SOD, and MDA detection kits, immunofluorescence, and flow cytometry assays were performed to study the function of AQP4 and TRPV4 in DR rats. Results found that AQP4 and TRPV4 were overexpressed in HG-induced Muller cells and streptozotocin-induced DR rats. AQP4 inhibition promoted proliferation and cell cycle progression, repressed cell apoptosis, ferroptosis, and oxidative stress, and alleviated retinal injury in DR rats. Mechanistically, AQP4 positively regulated TRPV4 expression. Overexpression of TRPV4 enhanced ferroptosis and oxidative stress in HG-treated Muller cells, and inhibition of TRPV4 had a protective effect on DR-induced retinal injury in rats. In conclusion, inhibition of AQP4 inhibits the ferroptosis and oxidative stress in Muller cells by downregulating TRPV4, which may be a potential target for DR therapy.
Topics: Animals; Male; Mice; Rats; Aquaporin 4; Diabetes Mellitus, Experimental; Diabetic Retinopathy; Ependymoglial Cells; Ferroptosis; Glucose; Mice, Inbred C57BL; Oxidative Stress; Rats, Sprague-Dawley; TRPV Cation Channels
PubMed: 38735619
DOI: 10.1016/j.yexcr.2024.114087 -
Cells Apr 2021The ability to regenerate tissues varies between species and between tissues within a species. Mammals have a limited ability to regenerate tissues, whereas zebrafish... (Review)
Review
The ability to regenerate tissues varies between species and between tissues within a species. Mammals have a limited ability to regenerate tissues, whereas zebrafish possess the ability to regenerate almost all tissues and organs, including fin, heart, kidney, brain, and retina. In the zebrafish brain, injury and cell death activate complex signaling networks that stimulate radial glia to reprogram into neural stem-like cells that repair the injury. In the retina, a popular model for investigating neuronal regeneration, Müller glia, radial glia unique to the retina, reprogram into stem-like cells and undergo a single asymmetric division to generate multi-potent retinal progenitors. Müller glia-derived progenitors then divide rapidly, numerically matching the magnitude of the cell death, and differentiate into the ablated neurons. Emerging evidence reveals that inflammation plays an essential role in this multi-step process of retinal regeneration. This review summarizes the current knowledge of the inflammatory events during retinal regeneration and highlights the mechanisms whereby inflammatory molecules regulate the quiescence and division of Müller glia, the proliferation of Müller glia-derived progenitors and the survival of regenerated neurons.
Topics: Animals; Cellular Reprogramming; Ependymoglial Cells; Inflammation; Neurogenesis; Regeneration; Retina; Zebrafish
PubMed: 33916186
DOI: 10.3390/cells10040783 -
Acta Ophthalmologica Feb 2020Galectin-1 regulates endothelial cell function and promotes angiogenesis. We investigated the hypothesis that galectin-1 may be involved in the pathogenesis of...
PURPOSE
Galectin-1 regulates endothelial cell function and promotes angiogenesis. We investigated the hypothesis that galectin-1 may be involved in the pathogenesis of proliferative diabetic retinopathy (PDR).
METHODS
Vitreous samples from 36 PDR and 20 nondiabetic patients, epiretinal fibrovascular membranes from 13 patients with PDR, rat retinas and human retinal Müller glial cells were studied by enzyme-linked immunosorbent assay (ELISA), immunohistochemistry and Western blot analysis. In vitro angiogenesis assays were performed and the adherence of leukocytes to galectin-1-stimulated human retinal microvascular endothelial cells (HRMECs) was assessed.
RESULTS
The ELISA analysis revealed that galectin-1 and vascular endothelial growth factor (VEGF) levels were significantly higher in vitreous samples from PDR patients than in those from nondiabetics (p < 0.001 for both comparisons). A significant positive correlation was found between the levels of galectin-1 and VEGF (r = 0.354; p = 0.022). In epiretinal membranes, immunohistochemical analysis showed that galectin-1 was expressed in vascular endothelial cells expressing CD31, myofibroblasts expressing α-smooth muscle actin and leukocytes expressing CD45. The galectin-1 receptor neuropilin-1 was expressed on vascular endothelial cells. CD31 staining was used as a marker to assess microvessel density (MVD). Significant positive correlation was detected between MVD in epiretinal membranes and the number of blood vessels expressing galectin-1 (r = 0.848; p < 0.001). Western blot analysis demonstrated significant increase of galectin-1 protein in rat retinas after induction of diabetes. ELISA analysis revealed that hydrogen peroxide and cobalt chloride (CoCl ) induced upregulation of galectin-1 in Müller cells. Treatment with galectin-1 induced upregulation of VEGF in Müller cells and increased leukocyte adhesion to HRMECs. The galectin-1 inhibitor OTX008 attenuated VEGF-induced HRMECs migration and CoCl -induced upregulation of NF-κB, galectin-1 and VEGF in Müller cells.
CONCLUSIONS
These results suggest that galectin-1is involved in the pathogenesis of PDR.
Topics: Adult; Aged; Aged, 80 and over; Animals; Biomarkers; Blotting, Western; Cells, Cultured; Diabetes Mellitus, Experimental; Diabetic Retinopathy; Enzyme-Linked Immunosorbent Assay; Ependymoglial Cells; Female; Galectin 1; Humans; Immunohistochemistry; Male; Middle Aged; Rats; Rats, Sprague-Dawley; Vitrectomy; Vitreous Body; Young Adult
PubMed: 31318490
DOI: 10.1111/aos.14191 -
Ophthalmic Research 2019Lamellar macular hole (LMH) is a vitreoretinal disorder characterized by an irregular foveal contour, a break in the inner fovea, dehiscence of the inner foveal retina... (Review)
Review
Lamellar macular hole (LMH) is a vitreoretinal disorder characterized by an irregular foveal contour, a break in the inner fovea, dehiscence of the inner foveal retina from the outer retina, and the absence of a full-thickness foveal defect with intact foveal photoreceptors. The pathogenesis is only partially known. The advent of high-resolution optical coherence tomography has allowed distinguishing between two types of epiretinal membrane (ERM) associated with LMH: a conventional ERM (commonly found in macular pucker) and an atypical ERM (known by varied names: dense, epiretinal proliferation, or degenerative). These two types of ERM not only influence LMH morphology but also differ in cell and collagen composition. It remains unclear if these two types are indeed two distinct clinical entities or rather two stages of the same macular disorder. Studies of the natural evolution of LMH have not fully resolved this issue and also offered variable results. Surgical treatment leads to excellent anatomical and functional outcomes, but not without risks. This review provides a critical summary of the available data on LMH including some new insights.
Topics: Ependymoglial Cells; Epiretinal Membrane; Fovea Centralis; Humans; Retinal Perforations; Retrospective Studies; Tomography, Optical Coherence; Visual Acuity
PubMed: 30625477
DOI: 10.1159/000494687 -
Glia Apr 2017Müller cells are the dominant macroglial cells in the retina of all vertebrates. They fulfill a variety of functions important for retinal physiology, among them... (Review)
Review
Müller cells are the dominant macroglial cells in the retina of all vertebrates. They fulfill a variety of functions important for retinal physiology, among them spatial buffering of K ions and uptake of glutamate and other neurotransmitters. To this end, Müller cells express inwardly rectifying K channels and electrogenic glutamate transporters. Moreover, a lot of voltage- and ligand-gated ion channels, aquaporin water channels, and electrogenic transporters are expressed in Müller cells, some of them in a species-specific manner. For example, voltage-dependent Na channels are found exclusively in some but not all mammalian species. Whereas a lot of data exist from amphibians and mammals, the results from other vertebrates are sparse. It is the aim of this review to present a survey on Müller cell electrophysiology covering all classes of vertebrates. The focus is on functional studies, mainly performed using the whole-cell patch-clamp technique. However, data about the expression of membrane channels and transporters from immunohistochemistry are also included. Possible functional roles of membrane channels and transporters are discussed. Obviously, electrophysiological properties involved in the main functions of Müller cells developed early in vertebrate evolution. GLIA 2017;65:533-568.
Topics: Animals; Ependymoglial Cells; Humans; Membrane Potentials; Physiology, Comparative; Retina; Vertebrates
PubMed: 27767232
DOI: 10.1002/glia.23082 -
Trends in Endocrinology and Metabolism:... Apr 2020Müller cells are glia that play important regulatory roles in retinal metabolism. These roles have been evolutionarily conserved across at least 300 million years.... (Review)
Review
Müller cells are glia that play important regulatory roles in retinal metabolism. These roles have been evolutionarily conserved across at least 300 million years. Müller cells have a tightly locked metabolic signature in the healthy retina, which rapidly degrades in response to insult and disease. This variation in metabolic signature occurs in a chaotic fashion, involving some central metabolic pathways. The cause of this divergence of Müller cells, from a single class with a unique metabolic signature to numerous separable metabolic classes, is currently unknown and illuminates potential alternative metabolic pathways that may be revealed in disease. Understanding the impacts of this heterogeneity on degenerate retinas and the implications for the metabolic support of surrounding neurons will be critical to long-term integration of retinal therapeutics for the restoration of visual perception following photoreceptor degeneration.
Topics: Ependymoglial Cells; Glutamate-Ammonia Ligase; Humans; Metabolome; Retinal Degeneration
PubMed: 32187524
DOI: 10.1016/j.tem.2020.01.005 -
Cells Jul 2021Müller glia, the major glial cell types in the retina, maintain retinal homeostasis and provide structural support to retinal photoreceptors. They also possess... (Review)
Review
Müller glia, the major glial cell types in the retina, maintain retinal homeostasis and provide structural support to retinal photoreceptors. They also possess regenerative potential that might be used for retinal repair in response to injury or disease. In teleost fish (such as zebrafish), the Müller glia response to injury involves reprogramming events that result in a population of proliferative neural progenitors that can regenerate the injured retina. Recent studies have revealed several important mechanisms for the regenerative capacity of Müller glia in fish, which may shed more light on the mechanisms of Müller glia reprogramming and regeneration in mammals. Mammalian Müller glia can adopt stem cell characteristics, and in response to special conditions, be persuaded to proliferate and regenerate, although their native regeneration potential is limited. In this review, we consider the work to date revealing the regenerative potential of the mammalian Müller glia and discuss whether they are a potential source for cell regeneration therapy in humans.
Topics: Animals; Cell Differentiation; Cell Proliferation; Ependymoglial Cells; Humans; Regeneration; Retina; Retinal Diseases; Signal Transduction; Stem Cells
PubMed: 34440726
DOI: 10.3390/cells10081957