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Vision Research Oct 2017Müller cells are one of the primary glial cell types found in the retina and play a significant role in maintaining retinal function and health. Since Müller cells are... (Review)
Review
Müller cells are one of the primary glial cell types found in the retina and play a significant role in maintaining retinal function and health. Since Müller cells are the only cell type to span the entire width of the retina and have contact to almost every cell type in the retina they are uniquely positioned to perform a wide variety of functions necessary to maintaining retinal homeostasis. In the healthy retina, Müller cells recycle neurotransmitters, prevent glutamate toxicity, redistribute ions by spatial buffering, participate in the retinoid cycle, and regulate nutrient supplies by multiple mechanisms. Any disturbance to the retinal environment is going to influence proper Müller cell function and well being which in turn will affect the entire retina. This is evident in a disease like diabetic retinopathy where Müller cells contribute to neuronal dysfunction, the production of pro-angiogenic factors leading to neovascularization, the set up of a chronic inflammatory retinal environment, and eventual cell death. In this review, we highlight the importance of Müller cells in maintaining a healthy and functioning retina and discuss various pathological events of diabetic retinopathy in which Müller cells seem to play a crucial role. The beneficial and detrimental effects of cytokine and growth factor production by Müller cells on the microvasculature and retinal neuronal tissue will be outlined. Understanding Müller cell functions within the retina and restoring such function in diabetic retinopathy should become a cornerstone for developing effective therapies to treat diabetic retinopathy.
Topics: Animals; Cytokines; Diabetic Retinopathy; Ependymoglial Cells; Humans; Intercellular Signaling Peptides and Proteins
PubMed: 28866025
DOI: 10.1016/j.visres.2017.03.013 -
Physiology & Behavior May 2023Reciprocal communication between neurons and glia is essential for normal brain functioning and adequate physiological functions, including energy balance. In... (Review)
Review
Reciprocal communication between neurons and glia is essential for normal brain functioning and adequate physiological functions, including energy balance. In vertebrates, the homeostatic process that adjusts food intake and energy expenditure in line with physiological requirements is tightly controlled by numerous neural cell types located within the hypothalamus and the brainstem and organized in complex networks. Within these neural networks, peculiar ependymoglial cells called tanycytes are nowadays recognized as multifunctional players in the physiological mechanisms of appetite control, partly by modulating orexigenic and anorexigenic neurons. Here, we review recent advances in tanycytes' impact on hypothalamic neuronal activity, emphasizing on arcuate neurons.
Topics: Animals; Ependymoglial Cells; Hypothalamus; Neurons; Neuroglia; Brain; Energy Metabolism
PubMed: 36740135
DOI: 10.1016/j.physbeh.2023.114108 -
Investigative Ophthalmology & Visual... Jul 2023Diabetic macular edema (DME) is a common complication of diabetic retinopathy and is the leading cause of vision loss in diabetic patients. Various factors, such as... (Review)
Review
Diabetic macular edema (DME) is a common complication of diabetic retinopathy and is the leading cause of vision loss in diabetic patients. Various factors, such as metabolic disorders and inflammation caused by hyperglycemia, are involved in the occurrence and development of DME, but the specific mechanism is still unclear. Müller cells are a type of macroglial cell unique to the fundus, distributed throughout the retina, and they play a unique role in retinal homeostasis. This article reviews the role of Müller cells in the pathological process of DME and the research progress in the treatment of DME by targeting Müller cells through gene therapy.
Topics: Humans; Diabetic Retinopathy; Macular Edema; Ependymoglial Cells; Retina; Fundus Oculi; Diabetes Mellitus
PubMed: 37418272
DOI: 10.1167/iovs.64.10.8 -
BMC Ophthalmology Nov 2022Changes in the retina and choroid blood vessels are regularly observed in myopia. However, if the retinal glial cells, which directly contact blood vessels, play a role...
BACKGROUND
Changes in the retina and choroid blood vessels are regularly observed in myopia. However, if the retinal glial cells, which directly contact blood vessels, play a role in mammalian myopia is unknown. We aimed to explore the potential role and mechanism of retinal glial cells in form deprived myopia.
METHODS
We adapted the mice form-deprivation myopia model by covering the right eye and left the left eye open for control, measured the ocular structure with anterior segment optical coherence tomography, evaluated changes in the morphology and distribution of retinal glial cells by fluorescence staining and western blotting; we also searched the online GEO databases to obtain relative gene lists and confirmed them in the form-deprivation myopia mouse retina at mRNA and protein level.
RESULTS
Compared with the open eye, the ocular axial length (3.54 ± 0.006 mm v.s. 3.48 ± 0.004 mm, p = 0.027) and vitreous chamber depth (3.07 ± 0.005 mm v.s. 2.98 ± 0.006 mm, p = 0.007) in the covered eye became longer. Both glial fibrillary acidic protein and excitatory amino acid transporters 4 elevated. There were 12 common pathways in human myopia and anoxic astrocytes. The key proteins were also highly relevant to atropine target proteins. In mice, two common pathways were found in myopia and anoxic Müller cells. Seven main genes and four key proteins were significantly changed in the mice form-deprivation myopia retinas.
CONCLUSION
Retinal astrocytes and Müller cells were activated in myopia. They may response to stimuli and secretory acting factors, and might be a valid target for atropine.
Topics: Humans; Mice; Animals; Ependymoglial Cells; Astrocytes; Neuroglia; Myopia; Atropine; Retina; Disease Models, Animal; Hypoxia; Mammals
PubMed: 36418970
DOI: 10.1186/s12886-022-02643-0 -
Stem Cell Reports Dec 2023In mammals, loss of retinal cells due to disease or trauma is an irreversible process that can lead to blindness. Interestingly, regeneration of retinal neurons is a...
In mammals, loss of retinal cells due to disease or trauma is an irreversible process that can lead to blindness. Interestingly, regeneration of retinal neurons is a well established process in some non-mammalian vertebrates and is driven by the Müller glia (MG), which are able to re-enter the cell cycle and reprogram into neurogenic progenitors upon retinal injury or disease. Progress has been made to restore this mechanism in mammals to promote retinal regeneration: MG can be stimulated to generate new neurons in vivo in the adult mouse retina after the over-expression of the pro-neural transcription factor Ascl1. In this study, we applied the same strategy to reprogram human MG derived from fetal retina and retinal organoids into neurons. Combining single cell RNA sequencing, single cell ATAC sequencing, immunofluorescence, and electrophysiology we demonstrate that human MG can be reprogrammed into neurogenic cells in vitro.
Topics: Animals; Mice; Humans; Neuroglia; Neurogenesis; Neurons; Retina; Mammals; Ependymoglial Cells; Cell Proliferation; Basic Helix-Loop-Helix Transcription Factors
PubMed: 38039971
DOI: 10.1016/j.stemcr.2023.10.021 -
FEBS Letters Dec 2017The ventral telencephalon is the developmental origin of the basal ganglia and the source of neuronal and glial cells that integrate into developing circuits in other... (Review)
Review
The ventral telencephalon is the developmental origin of the basal ganglia and the source of neuronal and glial cells that integrate into developing circuits in other areas of the brain. Radial glia in the embryonic subpallium give rise to an enormous diversity of mature cell types, either directly or through other transit-amplifying progenitors. Here, we review current knowledge about these subpallial neural stem cells and their progeny, focusing on the period of neurogenesis. We describe their cell biological features and the extrinsic and intrinsic molecular codes that guide their fate specification in defined temporal and spatial sequences. We also discuss the role of clonal lineage in the organization and specification of mature neurons.
Topics: Animals; Cell Differentiation; Cell Lineage; Ependymoglial Cells; Humans; Neural Stem Cells; Neurogenesis; Neuroglia; Neurons; Telencephalon
PubMed: 28862741
DOI: 10.1002/1873-3468.12829 -
Cell Reports Dec 2022Multiciliated ependymal cells and adult neural stem cells are components of the adult neurogenic niche, essential for brain homeostasis. These cells share a common glial...
Multiciliated ependymal cells and adult neural stem cells are components of the adult neurogenic niche, essential for brain homeostasis. These cells share a common glial cell lineage regulated by the Geminin family members Geminin and GemC1/Mcidas. Ependymal precursors require GemC1/Mcidas expression to massively amplify centrioles and become multiciliated cells. Here, we show that GemC1-dependent differentiation is initiated in actively cycling radial glial cells, in which a DNA damage response, including DNA replication-associated damage and dysfunctional telomeres, is induced, without affecting cell survival. Genotoxic stress is not sufficient by itself to induce ependymal cell differentiation, although the absence of p53 or p21 in progenitors hinders differentiation by maintaining cell division. Activation of the p53-p21 pathway downstream of GemC1 leads to cell-cycle slowdown/arrest, which permits timely onset of ependymal cell differentiation in progenitor cells.
Topics: Geminin; Tumor Suppressor Protein p53; Ependyma; Ependymoglial Cells; Neural Stem Cells; Cell Differentiation
PubMed: 36516767
DOI: 10.1016/j.celrep.2022.111810 -
Journal of Pharmacological Sciences Mar 2021Glaucoma, a progressive optic neuropathy and the leading cause of blindness, is characterized by impairment or degeneration of retinal ganglion cells (RGCs), which... (Review)
Review
Glaucoma, a progressive optic neuropathy and the leading cause of blindness, is characterized by impairment or degeneration of retinal ganglion cells (RGCs), which transmit visual information to the brain. Currently, 70 million people worldwide are affected by glaucoma. Elevated intraocular pressure (IOP), a major risk factor of glaucoma, directly damages RGCs. However, a substantial proportion of glaucoma patients have a normal IOP level. In particular, over 90% of Japanese glaucoma patients are reported to have normal IOP levels. Thus, a new focus for glaucoma pathology has emerged. Glial cells contribute to tissue homeostasis. Under pathological conditions, glial cells become reactive, lose their homeostatic functions, and gain neurotoxic functions, which trigger neurodegeneration in several diseases including glaucoma. Reactive glial cells have been identified in the eyes of glaucoma patients. In a glaucoma animal model, reactive glial cells are observed at early stages of the disease when RGCs are intact, indicating the possible role of glial cells in the pathogenesis of glaucoma. In this review, we introduce potential roles of glial cells in the pathogenesis of glaucoma. We focus on the roles of the ocular macroglial cells such as astrocytes and Müller cells, and discuss their roles in the pathogenesis of glaucoma.
Topics: Astrocytes; Complement C3; Ependymoglial Cells; Glaucoma; Gliosis; Glutamic Acid; Humans; Intraocular Pressure; Nerve Growth Factors; Optic Disk; Retina; Risk Factors; STAT3 Transcription Factor
PubMed: 33602506
DOI: 10.1016/j.jphs.2020.12.009 -
Disease Models & Mechanisms Sep 2023Diabetic retinopathy (DR) is characterised by dysfunction of the retinal neurovascular unit, leading to visual impairment and blindness. Müller cells are key components...
Diabetic retinopathy (DR) is characterised by dysfunction of the retinal neurovascular unit, leading to visual impairment and blindness. Müller cells are key components of the retinal neurovascular unit and diabetes has a detrimental impact on these glial cells, triggering progressive neurovascular pathology of DR. Amongst many factors expressed by Müller cells, interleukin-33 (IL-33) has an established immunomodulatory role, and we investigated the role of endogenous IL-33 in DR. The expression of IL-33 in Müller cells increased during diabetes. Wild-type and Il33-/- mice developed equivalent levels of hyperglycaemia and weight loss following streptozotocin-induced diabetes. Electroretinogram a- and b-wave amplitudes, neuroretina thickness, and the numbers of cone photoreceptors and ganglion cells were significantly reduced in Il33-/- diabetic mice compared with those in wild-type counterparts. The Il33-/- diabetic retina also exhibited microglial activation, sustained gliosis, and upregulation of pro-inflammatory cytokines and neurotrophins. Primary Müller cells from Il33-/- mice expressed significantly lower levels of neurotransmitter-related genes (Glul and Slc1a3) and neurotrophin genes (Cntf, Lif, Igf1 and Ngf) under high-glucose conditions. Our results suggest that deletion of IL-33 promotes inflammation and neurodegeneration in DR, and that this cytokine is critical for regulation of glutamate metabolism, neurotransmitter recycling and neurotrophin secretion by Müller cells.
Topics: Animals; Mice; Cytokines; Diabetes Mellitus, Experimental; Diabetic Retinopathy; Ependymoglial Cells; Inflammation; Interleukin-33; Retina
PubMed: 37671525
DOI: 10.1242/dmm.050174 -
ELife Dec 2022-methyladenosine (mA) is the most prevalent mRNA internal modification and has been shown to regulate the development, physiology, and pathology of various tissues....
-methyladenosine (mA) is the most prevalent mRNA internal modification and has been shown to regulate the development, physiology, and pathology of various tissues. However, the functions of the mA epitranscriptome in the visual system remain unclear. In this study, using a retina-specific conditional knockout mouse model, we show that retinas deficient in , the core component of the mA methyltransferase complex, exhibit structural and functional abnormalities beginning at the end of retinogenesis. Immunohistological and single-cell RNA sequencing (scRNA-seq) analyses of retinogenesis processes reveal that retinal progenitor cells (RPCs) and Müller glial cells are the two cell types primarily affected by deficiency. Integrative analyses of scRNA-seq and MeRIP-seq data suggest that mA fine-tunes the transcriptomic transition from RPCs to Müller cells by promoting the degradation of RPC transcripts, the disruption of which leads to abnormalities in late retinogenesis and likely compromises the glial functions of Müller cells. Overexpression of mA-regulated RPC transcripts in late RPCs partially recapitulates the -deficient retinal phenotype. Collectively, our study reveals an epitranscriptomic mechanism governing progenitor-to-glial cell transition during late retinogenesis, which is essential for the homeostasis of the mature retina. The mechanism revealed in this study might also apply to other nervous systems.
Topics: Animals; Mice; Neuroglia; Neural Stem Cells; Retina; Ependymoglial Cells; Homeostasis; Mice, Knockout
PubMed: 36459087
DOI: 10.7554/eLife.79994