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[Zhonghua Yan Ke Za Zhi] Chinese... Nov 2023Müller cells are important glial cells in the retina, which play important roles in maintaining the stability of the retina by mechanical support, homeostasis, and...
Müller cells are important glial cells in the retina, which play important roles in maintaining the stability of the retina by mechanical support, homeostasis, and physiological metabolism, as well as protecting photoreceptor cells and retinal pigment epithelial cells. The degeneration and destruction of Müller cells are often accompanied by various retinal diseases, and the function of Müller cells is changed under pathological conditions. Based on the summary of the morphology, distribution and function of Müller cells, this article analyzes the different manifestations and changes of Müller cells in different stages of macular hole and the closely related mechanisms, aiming to clarify the role of Müller cells in the formation and development of macular hole and to provide reference for the prediction of disease progression and guidance of treatment.(This article was published ahead of print on the official website of Chinese Journal of Ophthalmology on Augest 28, 2023).
Topics: Humans; Ependymoglial Cells; Retinal Perforations; Retina; Photoreceptor Cells; Retinal Diseases; Neuroglia
PubMed: 37641407
DOI: 10.3760/cma.j.cn112142-20230627-00246 -
Current Eye Research Mar 2020Retinal degeneration is a leading cause of untreatable blindness in the industrialised world. It is typically irreversible and there are few curative treatments... (Review)
Review
Retinal degeneration is a leading cause of untreatable blindness in the industrialised world. It is typically irreversible and there are few curative treatments available. The use of stem cells to generate new retinal neurons for transplantation purposes has received significant interest in recent years and is beginning to move towards clinical trials. However, such approaches are likely to be most effective for relatively focal areas of repair. An intriguing complementary approach is endogenous self-repair. Retinal cells from the ciliary marginal zone (CMZ), retinal pigment epithelium (RPE) and Müller glial cells (MG) have all been shown to play a role in retinal repair, typically in lower vertebrates. Among them, MG have received renewed interest, due to their distribution throughout (centre to periphery) the neural retina and their potential to re-acquire a progenitor-like state following retinal injury with the ability to proliferate and generate new neurons. Triggering these innate self-repair mechanisms represents an exciting therapeutic option in treating retinal degeneration. However, these cells behave differently in mammalian and non-mammalian species, with a considerably restricted potential in mammals. In this short review, we look at some of the recent progress made in our understanding of the signalling pathways that underlie MG-mediated regeneration in lower vertebrates, and some of the challenges that have been revealed in our attempts to reactivate this process in the mammalian retina.
Topics: Animals; Ependymoglial Cells; Humans; Neuroglia; Regeneration; Retinal Degeneration; Retinal Neurons
PubMed: 31557060
DOI: 10.1080/02713683.2019.1669665 -
Redox Biology Aug 2022The Pentose Phosphate Pathway (PPP), a metabolic offshoot of the glycolytic pathway, provides protective metabolites and molecules essential for cell redox balance and...
The Pentose Phosphate Pathway (PPP), a metabolic offshoot of the glycolytic pathway, provides protective metabolites and molecules essential for cell redox balance and survival. Transketolase (TKT) is the critical enzyme that controls the extent of "traffic flow" through the PPP. Here, we explored the role of TKT in maintaining the health of the human retina. We found that Müller cells were the primary retinal cell type expressing TKT in the human retina. We further explored the role of TKT in human Müller cells by knocking down its expression in primary cultured Müller cells (huPMCs), isolated from the human retina (11 human donors in total), under light-induced oxidative stress. TKT knockdown and light stress reduced TKT enzymatic activities and the overall metabolic activities of huPMCs with no detectable cell death. TKT knockdown restrained the PPP traffic flow, reduced the expression of NAD(P)H Quinone Dehydrogenase 1 (NQO1), impaired the antioxidative response of NRF2 to light stress and aggravated the endoplasmic reticulum (ER) stress. TKT knockdown also inhibited overall glucose intake, reduced expression of Dihydrolipoamide dehydrogenase (DLD) and impaired the energy supply of the huPMCs. In summary, Müller cell-mediated TKT activity plays a critical protective role in the stressed retina. Knockdown of TKT disrupted the PPP and impaired overall glucose utilisation by huPMCs and rendered huPMCs more vulnerable to light stress by impairing energy supply and antioxidative NRF2 responses.
Topics: Ependymoglial Cells; Glucose; Humans; NF-E2-Related Factor 2; Pentose Phosphate Pathway; Pentoses; Phosphates; Transketolase
PubMed: 35779441
DOI: 10.1016/j.redox.2022.102379 -
Advances in Experimental Medicine and... 2016In the adult zebrafish, death of retinal neurons stimulates Müller glia to re-enter the cell cycle to produce neuronal progenitor cells (NPCs) that undergo further cell... (Review)
Review
In the adult zebrafish, death of retinal neurons stimulates Müller glia to re-enter the cell cycle to produce neuronal progenitor cells (NPCs) that undergo further cell divisions and differentiate to replace lost neurons in the correct spatial locations. Understanding the mechanisms regulating retinal regeneration will ultimately provide avenues to overcome vision loss in human. Recently, the observation of interkinetic nuclear migration (INM) of Müller glia in the regenerating zebrafish retina resulted in the inclusion of an additional complex step to the regeneration process. The pathways regulating INM and its function in the regenerating retina have not been well studied. Here, we summarize the evidence for INM in the regenerating retina and review mechanisms that control INM during neuro-epithelial development in the context of pathways known to be critical during retinal regeneration.
Topics: Animals; Cell Movement; Cell Nucleus; Ependymoglial Cells; Humans; Neurogenesis; Regeneration; Retina; Retinal Neurons; Zebrafish
PubMed: 26427463
DOI: 10.1007/978-3-319-17121-0_78 -
International Journal of Molecular... Aug 2016The main water channel of the brain, aquaporin-4 (AQP4), is one of the classical water-specific aquaporins. It is expressed in many epithelial tissues in the basolateral... (Review)
Review
The main water channel of the brain, aquaporin-4 (AQP4), is one of the classical water-specific aquaporins. It is expressed in many epithelial tissues in the basolateral membrane domain. It is present in the membranes of supporting cells in most sensory organs in a specifically adapted pattern: in the supporting cells of the olfactory mucosa, AQP4 occurs along the basolateral aspects, in mammalian retinal Müller cells it is highly polarized. In the cochlear epithelium of the inner ear, it is expressed basolaterally in some cells but strictly basally in others. Within the central nervous system, aquaporin-4 (AQP4) is expressed by cells of the astroglial family, more specifically, by astrocytes and ependymal cells. In the mammalian brain, AQP4 is located in high density in the membranes of astrocytic endfeet facing the pial surface and surrounding blood vessels. At these locations, AQP4 plays a role in the maintenance of ionic homeostasis and volume regulation. This highly polarized expression has not been observed in the brain of fish where astroglial cells have long processes and occur mostly as radial glial cells. In the brain of the zebrafish, AQP4 immunoreactivity is found along the radial extent of astroglial cells. This suggests that the polarized expression of AQP4 was not present at all stages of evolution. Thus, a polarized expression of AQP4 as part of a control mechanism for a stable ionic environment and water balanced occurred at several locations in supporting and glial cells during evolution. This initially basolateral membrane localization of AQP4 is shifted to highly polarized expression in astrocytic endfeet in the mammalian brain and serves as a part of the neurovascular unit to efficiently maintain homeostasis.
Topics: Animals; Aquaporin 4; Astrocytes; Brain; Ependymoglial Cells; Humans; Olfactory Mucosa; Water
PubMed: 27571065
DOI: 10.3390/ijms17091411 -
International Journal of Molecular... Mar 2017Anti-vascular endothelial growth factor (VEGF) therapy has revolutionized the treatment of retinal vascular diseases. However, constitutive VEGF also acts as a trophic...
Anti-vascular endothelial growth factor (VEGF) therapy has revolutionized the treatment of retinal vascular diseases. However, constitutive VEGF also acts as a trophic factor on retinal nonvascular cells. We have studied the effects of aflibercept and ranibizumab on human Müller cells and photoreceptors exposed to starvation media containing various concentrations of glucose, with or without CoCl2-induced hypoxia. Cell survival was assessed by calcein-AM cell viability assays. Expression of heat shock proteins (Hsp) and redox proteins thioredoxin 1 and 2 (TRX1, TRX2) was studied by Western blots. The production of neurotrophic factors in Müller cells and interphotoreceptor retinoid-binding protein (IRBP) in photoreceptors was measured by enzymelinked immunosorbent assays. Aflibercept and ranibizumab did not affect the viability of both types of cells. Neither aflibercept nor ranibizumab affected the production of neurotrophic factors or expression of Hsp60 and Hsp90 in Müller cells. However, aflibercept but not ranibizumab affected the expression of Hsp60, Hsp9, TRX1 and TRX2 in photoreceptors. Aflibercept and ranibizumab both inhibited the production of IRBP in photoreceptors, aflibercept more so than ranibizumab. Our data indicates that the potential influence of aflibercept and ranibizumab on photoreceptors should be specifically monitored in clinical studies.
Topics: Angiogenesis Inhibitors; Cell Survival; Cells, Cultured; Ependymoglial Cells; Eye Proteins; Gene Expression; Glucose; Heat-Shock Proteins; Humans; Hypoxia; Nerve Growth Factors; Photoreceptor Cells; Ranibizumab; Receptors, Vascular Endothelial Growth Factor; Recombinant Fusion Proteins; Retinol-Binding Proteins; Stress, Physiological; Thioredoxins
PubMed: 28257068
DOI: 10.3390/ijms18030533 -
Journal of Cellular and Molecular... Feb 2019Retinal Müller glial cells have the potential of neurogenic retinal progenitor cells, and could reprogram into retinal-specific cell types such as photoreceptor cells....
Retinal Müller glial cells have the potential of neurogenic retinal progenitor cells, and could reprogram into retinal-specific cell types such as photoreceptor cells. How to promote the differentiation of Müller cells into photoreceptor cells represents a promising therapy strategy for retinal degeneration diseases. This study aimed to enhance the transdifferentiation of rat Müller cells-derived retinal stem cells (MC-RSCs) into photoreceptor-like cells and explore the signalling mechanism. We dedifferentiated rat Müller cells into MC-RSCs which were infected with Otx2 overexpression lentivirus or control. The positive rate of photoreceptor-like cells among MC-RSCs treated with Otx2 overexpression lentivirus was significantly higher compared to control. Furthermore, pre-treatment with Crx siRNA, Nrl siRNA, or GSK-3 inhibitor SB-216763 reduced the positive rate of photoreceptor-like cells among MC-RSCs treated with Otx2 overexpression lentivirus. Finally, Otx2 induced photoreceptor precursor cells were injected into subretinal space of N-methyl-N-nitrosourea induced rat model of retinal degeneration and partially recovered retinal degeneration in the rats. In conclusion, Otx2 enhances transdifferentiation of MC-RSCs into photoreceptor-like cells and this is associated with the inhibition of Wnt signalling. Otx2 is a potential target for gene therapy of retinal degenerative diseases.
Topics: Animals; Cell Differentiation; Cell Transdifferentiation; Ependymoglial Cells; Female; Glycogen Synthase Kinase 3; Indoles; Lentivirus; Maleimides; Neurons; Otx Transcription Factors; Photoreceptor Cells; Rats; Rats, Sprague-Dawley; Retina; Retinal Degeneration; Stem Cells
PubMed: 30451368
DOI: 10.1111/jcmm.13995 -
Stem Cell Research Feb 2023Müller glia are non-neuronal support cells that play a vital role in the homeostasis of the eye. Their radial-oriented processes span the width of the retina and... (Review)
Review
Müller glia are non-neuronal support cells that play a vital role in the homeostasis of the eye. Their radial-oriented processes span the width of the retina and respond to injury through a cellular response that can be detrimental or protective depending on the context. In some species, protective responses include the expression of stem cell-like genes which help to fuel new neuron formation and even restoration of vision. In many lower vertebrates including fish and amphibians, this response is well documented, however, in mammals it is severely limited. The remarkable plasticity of cellular reprogramming in lower vertebrates has inspired studies in mammals for repairing the retina and restoring sight, and recent studies suggest that mammals are also capable of regeneration, albeit to a lesser degree. Endogenous regeneration, whereby new retinal neurons are created from existing support cells, offers an exciting alternative approach to existing tissue transplant, gene therapy, and neural prosthetic approaches being explored in parallel. This review will highlight the role of Müller glia during retinal injury and repair. In the end, prospects for advancing retinal regeneration research will be considered.
Topics: Animals; Cellular Reprogramming; Neuroglia; Retina; Ependymoglial Cells; Neurons; Cell Proliferation; Mammals
PubMed: 36563542
DOI: 10.1016/j.scr.2022.103006 -
Experimental Eye Research Jan 2022Microglia and its interaction with Müller cells are responsible to retinal surveillance during retinal neurodegeneration, however, the role and mechanism of...
Microglia and its interaction with Müller cells are responsible to retinal surveillance during retinal neurodegeneration, however, the role and mechanism of microglia-derived tumor necrosis factor (TNF)-α in the activation of retinal Müller cells have not been fully elucidated. In the present study, primary microglia and Müller cells were isolated from newborn Sprague-Dawley (SD) rats with purities of 88.2 ± 6.2% and 92.2 ± 2.2%, respectively. By performing immunofluorescence and Western blot analysis, we found that TNF receptor (TNFR)-1 and TNFR2 were expressed in Müller cells. After co-cultured with microglia-conditioned medium (MCM), the elevated mRNA levels of glial fibrillary acidic protein (GFAP), proinflammatory factors (TNF-α, IL-1β, CXCL-1, CSF-1, NOS2, COX2) and decreased CNTF mRNA levels were found in Müller cells. However, pretreatment with R-7050 (a TNF-α receptor inhibitor) or anti-TNFR1 significantly abrogated the changes. Simultaneously, pretreatment with anti-TNFR2 slightly inhibited the expression of GFAP in MCM-incubated Müller cells. Meanwhile, anti-TNFR1 treatment reversed the increased expression of CSF-1 and IL-1β induced by TNF-α. Compared to the control groups, the phosphorylation of NF-κB P65, MAPK P38 and ERK1/2 in TNF-α-treated Müller cells was significantly increased. Nevertheless, pretreatment with anti-TNFR1 inhibited the phosphorylation of NF-κB P65 and MAPK p38, especially NF-κB P65. Additionally, pretreatment with Bay117082 (an NF-κB inhibitor) also significantly inhibited NF-κB P65 phosphorylation and GFAP expression. Moreover, anti-TNFR1 and Bay117082 treatment reduced NF-κB P65 phosphorylation of Müller cells induced by MCM. These results suggested that microglia-derived TNF-α served as a vital role in regulating Müller cells activation during retinal neurodegeneration.
Topics: Animals; Animals, Newborn; Blotting, Western; Cells, Cultured; Coculture Techniques; Culture Media, Conditioned; Ependymoglial Cells; Fluorescent Antibody Technique, Indirect; Glial Fibrillary Acidic Protein; Gliosis; Microglia; NF-kappa B; Phosphorylation; RNA, Messenger; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; Receptors, Tumor Necrosis Factor, Type I; Receptors, Tumor Necrosis Factor, Type II; Signal Transduction; Transcription Factor RelA; Tumor Necrosis Factor-alpha
PubMed: 34801535
DOI: 10.1016/j.exer.2021.108852 -
Microscopy and Microanalysis : the... Oct 2018Transparent cells in the vertebrate optical tract, such as lens fiber cells and corneal epithelium cells, have specialized proteins that somehow permit only a low level...
Transparent cells in the vertebrate optical tract, such as lens fiber cells and corneal epithelium cells, have specialized proteins that somehow permit only a low level of light scattering in their cytoplasm. It has been shown that both cell types contain (1) beaded intermediate filaments as well as (2) α-crystallin globulins. It is known that genetic and chemical alterations to these specialized proteins induce cytoplasmic opaqueness and visual complications. Crystallins were described previously in the retinal Müller cells of frogs. In the present work, using immunocytochemistry, fluorescence confocal imaging, and immuno-electron microscopy, we found that αA-crystallins are present in the cytoplasm of retinal Müller cells and in the photoreceptors of rats. Given that Müller glial cells were recently described as "living light guides" as were photoreceptors previously, we suggest that αA-crystallins, as in other highly transparent cells, allow Müller cells and photoreceptors to minimize intraretinal scattering during retinal light transmission.
Topics: Animals; Cytoplasm; Ependymoglial Cells; Eye; Immunohistochemistry; Lens, Crystalline; Light; Microscopy, Immunoelectron; Neuroglia; Optical Imaging; Photoreceptor Cells; Rats; Rats, Sprague-Dawley; Retina; Retinal Rod Photoreceptor Cells; alpha-Crystallin A Chain; alpha-Crystallins
PubMed: 30253817
DOI: 10.1017/S1431927618015118