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Clinica Chimica Acta; International... Jan 2017Müller Stem cells to treat ocular diseases has triggered enthusiasm across all medical and scientific communities. Recent development in the field of stem cells has... (Review)
Review
Müller Stem cells to treat ocular diseases has triggered enthusiasm across all medical and scientific communities. Recent development in the field of stem cells has widened the prospects of applying cell based therapies to regenerate ocular tissues that have been irreversibly damaged by disease or injury. Ocular tissues such as the lens and the retina are now known to possess cell having remarkable regenerative abilities. Recent studies have shown that the Müller glia, a cell found in all vertebrate retinas, is the primary source of new neurons, and therefore are considered as the cellular basis for retinal regeneration in mammalian retinas. Here, we review the current status of retinal regeneration of the human eye by Müller stem cells. This review elucidates the current status of retinal regeneration by Müller stem cells, along with major retinal degenerative diseases where these stem cells play regenerative role in retinal repair and replacement.
Topics: Animals; Ependymoglial Cells; Humans; Neural Stem Cells; Regeneration; Retina
PubMed: 27876464
DOI: 10.1016/j.cca.2016.11.030 -
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 -
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 -
International Journal of Molecular... Mar 2018Diabetic retinopathy is a common complication of diabetes and remains the leading cause of blindness among the working-age population. For decades, diabetic retinopathy... (Review)
Review
Diabetic retinopathy is a common complication of diabetes and remains the leading cause of blindness among the working-age population. For decades, diabetic retinopathy was considered only a microvascular complication, but the retinal microvasculature is intimately associated with and governed by neurons and glia, which are affected even prior to clinically detectable vascular lesions. While progress has been made to improve the vascular alterations, there is still no treatment to counteract the early neuro-glial perturbations in diabetic retinopathy. Diabetes is a complex metabolic disorder, characterized by chronic hyperglycemia along with dyslipidemia, hypoinsulinemia and hypertension. Increasing evidence points to inflammation as one key player in diabetes-associated retinal perturbations, however, the exact underlying molecular mechanisms are not yet fully understood. Interlinked molecular pathways, such as oxidative stress, formation of advanced glycation end-products and increased expression of vascular endothelial growth factor have received a lot of attention as they all contribute to the inflammatory response. In the current review, we focus on the involvement of inflammation in the pathophysiology of diabetic retinopathy with special emphasis on the functional relationships between glial cells and neurons. Finally, we summarize recent advances using novel targets to inhibit inflammation in diabetic retinopathy.
Topics: Animals; Astrocytes; Diabetic Retinopathy; Ependymoglial Cells; Humans; Inflammation; Neurodegenerative Diseases
PubMed: 29565290
DOI: 10.3390/ijms19040942 -
Journal of Ocular Pharmacology and... Oct 2016Müller glia, the principal macroglia of the retina, express diverse subtypes of adenosine and metabotropic purinergic (P2Y) receptors. Müller cells of several species,... (Review)
Review
Müller glia, the principal macroglia of the retina, express diverse subtypes of adenosine and metabotropic purinergic (P2Y) receptors. Müller cells of several species, including man, also express ionotropic P2X receptors. ATP is liberated from Müller cells after activation of metabotropic glutamate receptors and during osmotic and mechanical induction of membrane stretch; adenosine is released through equilibrative nucleoside transporters. Müller cell-derived purines modulate the neuronal activity and have autocrine effects, for example, induction of glial calcium waves and regulation of the cellular volume. Glial calcium waves induced by neuron-derived ATP mediate functional hyperemia in the retina. Purinergic signaling contributes to the induction of Müller cell gliosis, for example, of cellular proliferation and downregulation of potassium channels, which are important for the homeostatic functions of Müller cells. Purinergic glial calcium waves may also promote the long-range propagation of gliosis and neuronal degeneration across the retinal tissue. The osmotic ATP release is inhibited under pathological conditions. Inhibition of the ATP release may result in osmotic Müller cell swelling and dysregulation of the water transport through the cells; both may contribute to the development of retinal edema. Suppression of the osmotic ATP release and upregulation of the ecto-apyrase (NTPDase1), which facilitate the extracellular degradation of ATP and the formation of adenosine, may protect neurons and photoreceptors from death due to overactivation of P2X receptors. Pharmacological inhibition of P2X receptors and stimulation of adenosine receptors may represent clinical approaches to prevent retinal cell death and dysregulated cell proliferation, and to treat retinal edema.
Topics: Adenosine Triphosphate; Animals; Ependymoglial Cells; Humans; Purines; Receptors, Purinergic P2X7
PubMed: 27754822
DOI: 10.1089/jop.2016.0131 -
Advances in Experimental Medicine and... 2017This review article focuses on studies of Sigma 1 Receptor (Sigma1R) and retina . It provides a brief overview of the earliest pharmacological studies performed in the... (Review)
Review
This review article focuses on studies of Sigma 1 Receptor (Sigma1R) and retina . It provides a brief overview of the earliest pharmacological studies performed in the late 1990s that provided evidence of the presence of Sigma1R in various ocular tissues. It then describes work from a number of labs concerning the location of Sigma1R in several retinal cell types including ganglion, Müller glia , and photoreceptors . The role of Sigma1R ligands in retinal neuroprotection is emphasized. Early studies performed in vitro clearly showed that targeting Sigma1R could attenuate stress-induced retinal cell loss. These studies were followed by in vivo experiments. Data about the usefulness of targeting Sigma1R to prevent ganglion cell loss associated with diabetic retinopathy are reviewed. Mechanisms of Sigma1R-mediated retinal neuroprotection involving Müller cells , especially in modulating oxidative stress are described along with information about the retinal phenotype of mice lacking Sigma1R (Sigma1R mice). The retina develops normally in Sigma1R mice, but after many months there is evidence of apoptosis in the optic nerve head, decreased ganglion cell function and eventual loss of these cells. Additional studies using the Sigma1R mice provide strong evidence that in the retina, Sigma1R plays a key role in modulating cellular stress. Recent work has shown that targeting Sigma1R may extend beyond protection of ganglion cells to include photoreceptor cell degeneration as well.
Topics: Animals; Ependymoglial Cells; Humans; Oxidative Stress; Photoreceptor Cells; Receptors, sigma; Retina; Retinal Degeneration; Retinal Ganglion Cells; Sigma-1 Receptor
PubMed: 28315277
DOI: 10.1007/978-3-319-50174-1_18 -
ELife Oct 2023Mononuclear cells are involved in the pathogenesis of retinal diseases, including age-related macular degeneration (AMD). Here, we examined the mechanisms that underlie...
Mononuclear cells are involved in the pathogenesis of retinal diseases, including age-related macular degeneration (AMD). Here, we examined the mechanisms that underlie macrophage-driven retinal cell death. Monocytes were extracted from patients with AMD and differentiated into macrophages (hMdɸs), which were characterized based on proteomics, gene expression, and ex vivo and in vivo properties. Using bioinformatics, we identified the signaling pathway involved in macrophage-driven retinal cell death, and we assessed the therapeutic potential of targeting this pathway. We found that M2a hMdɸs were associated with retinal cell death in retinal explants and following adoptive transfer in a photic injury model. Moreover, M2a hMdɸs express several CCRI (C-C chemokine receptor type 1) ligands. Importantly, CCR1 was upregulated in Müller cells in models of retinal injury and aging, and CCR1 expression was correlated with retinal damage. Lastly, inhibiting CCR1 reduced photic-induced retinal damage, photoreceptor cell apoptosis, and retinal inflammation. These data suggest that hMdɸs, CCR1, and Müller cells work together to drive retinal and macular degeneration, suggesting that CCR1 may serve as a target for treating these sight-threatening conditions.
Topics: Humans; Animals; Retinal Degeneration; Ependymoglial Cells; Photoreceptor Cells; Retina; Macular Degeneration; Cell Death; Disease Models, Animal; Receptors, CCR1
PubMed: 37903056
DOI: 10.7554/eLife.81208 -
Journal of Extracellular Vesicles Sep 2022Cell-cell interactions in the central nervous system are based on the release of molecules mediating signal exchange and providing structural and trophic support through...
Cell-cell interactions in the central nervous system are based on the release of molecules mediating signal exchange and providing structural and trophic support through vesicular exocytosis and the formation of extracellular vesicles. The specific mechanisms employed by each cell type in the brain are incompletely understood. Here, we explored the means of communication used by Müller cells, a type of radial glial cells in the retina, which forms part of the central nervous system. Using immunohistochemical, electron microscopic, and molecular analyses, we provide evidence for the release of distinct extracellular vesicles from endfeet and microvilli of retinal Müller cells in adult mice in vivo. We identify VAMP5 as a Müller cell-specific SNARE component that is part of extracellular vesicles and responsive to ischemia, and we reveal differences between the secretomes of immunoaffinity-purified Müller cells and neurons in vitro. Our findings suggest extracellular vesicle-based communication as an important mediator of cellular interactions in the retina.
Topics: Animals; Ependymoglial Cells; Extracellular Vesicles; Mice; Neuroglia; Neurons; Retina
PubMed: 36043482
DOI: 10.1002/jev2.12254 -
Drug Discovery Today Aug 2019Müller cells are specialized glial cells that span the entire retina from the vitreous cavity to the subretinal space. Their functional diversity and unique radial... (Review)
Review
Müller cells are specialized glial cells that span the entire retina from the vitreous cavity to the subretinal space. Their functional diversity and unique radial morphology render them particularly interesting targets for new therapeutic approaches. In this review, we reflect on various possibilities for selective Müller cell targeting and describe how some of their cellular mechanisms can be used for retinal neuroprotection. Intriguingly, cross-species investigation of their properties has revealed that Müller cells also have an essential role in retinal regeneration. Although many questions regarding this subject remain, it is clear that Müller cells have unique characteristics that make them suitable targets for the prevention and treatment of numerous retinal diseases.
Topics: Animals; Ependymoglial Cells; Eye Diseases; Humans; Neuroglia; Ophthalmic Solutions; Retina
PubMed: 30731239
DOI: 10.1016/j.drudis.2019.01.023 -
Molecular and Cellular Endocrinology Oct 2023Reactive gliosis of Müller cells plays an important role in the pathogenesis of diabetic retinopathy (DR). Liraglutide, a glucagon-like peptide-1 receptor (GLP-1R)...
Reactive gliosis of Müller cells plays an important role in the pathogenesis of diabetic retinopathy (DR). Liraglutide, a glucagon-like peptide-1 receptor (GLP-1R) agonist, has been shown to improve DR by inhibiting reactive gliosis. However, the mechanism of inhibition has yet to be elucidated. This study investigated the effects of liraglutide on Müller glia reactivity in the early stages of DR and the underlying mechanisms. Proteomics combined with bioinformatics analysis, HE staining, and immunofluorescence staining revealed ganglion cell loss, reactive gliosis of Müller cells, and extracellular matrix (ECM) imbalance in rats with early stages of DR. High glucose (HG) exposure up-regulated GFAP and TNF-α expression and down-regulated ITGB1 expression and FN1 content in extracellular fluid in rMC1 cells, thereby promoting reactive gliosis. GLP-1R knockdown and HG+DAPT inhibition experiments show that liraglutide balances ECM levels by inhibiting activation of the Notch1/Hes1 pathway and ameliorates high-glucose-induced Müller glia reactivity. Thus, the study provides new targets and ideas for improvement of DR in early stages.
Topics: Rats; Animals; Liraglutide; Ependymoglial Cells; Gliosis; Diabetic Retinopathy; Inflammation; Extracellular Matrix; Glucose; Glucagon-Like Peptide-1 Receptor
PubMed: 37442365
DOI: 10.1016/j.mce.2023.112013