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Glia Apr 2020The human retina contains three types of glial cells: microglia and two types of macroglia, astrocytes and Müller cells. Macroglia provide homeostatic and metabolic... (Review)
Review
The human retina contains three types of glial cells: microglia and two types of macroglia, astrocytes and Müller cells. Macroglia provide homeostatic and metabolic support to photoreceptors and neurons required for neuronal activity. The fovea, the site of the sharpest vision which is astrocyte- and microglia-free, contains two populations of Müller glia: cells which form the Müller cell cone in the foveola and z-shaped Müller cells of the foveal walls. Both populations are characterized by morphological and functional differences. Müller cells of the foveola do not support the activity of photoreceptors and neurons, but provide the structural stability of the foveal tissue and improve the light transmission through the tissue to the photoreceptors. This article gives overviews of the glia of the human retina and the structure and function of both Müller cell types in the fovea, and describes the contributions of astrocytes and Müller cells to the ontogenetic development of the fovea.
Topics: Astrocytes; Ependymoglial Cells; Humans; Microglia; Retina
PubMed: 31793693
DOI: 10.1002/glia.23727 -
Progress in Retinal and Eye Research Mar 2016The mammalian retina provides an excellent opportunity to study glia-neuron interactions and the interactions of glia with blood vessels. Three main types of glial cells... (Review)
Review
The mammalian retina provides an excellent opportunity to study glia-neuron interactions and the interactions of glia with blood vessels. Three main types of glial cells are found in the mammalian retina that serve to maintain retinal homeostasis: astrocytes, Müller cells and resident microglia. Müller cells, astrocytes and microglia not only provide structural support but they are also involved in metabolism, the phagocytosis of neuronal debris, the release of certain transmitters and trophic factors and K(+) uptake. Astrocytes are mostly located in the nerve fibre layer and they accompany the blood vessels in the inner nuclear layer. Indeed, like Müller cells, astrocytic processes cover the blood vessels forming the retinal blood barrier and they fulfil a significant role in ion homeostasis. Among other activities, microglia can be stimulated to fulfil a macrophage function, as well as to interact with other glial cells and neurons by secreting growth factors. 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. The preferential involvement of the distinct glia cells in terms of the activity in the retina is discussed, for example, while Müller cells may serve as progenitors of retinal neurons, astrocytes and microglia are responsible for synaptic pruning. Since different types of glia participate together in certain activities in the retina, it is imperative to explore the order of redundancy and to explore the heterogeneity among these cells. Recent studies revealed the association of glia cell heterogeneity with specific functions. Finally, the neuroprotective effects of glia on photoreceptors and ganglion cells under normal and adverse conditions will also be explored.
Topics: Animals; Astrocytes; Blood Vessels; Cell Communication; Cell Differentiation; Ependymoglial Cells; Humans; Macrophages; Microglia; Retinal Ganglion Cells
PubMed: 26113209
DOI: 10.1016/j.preteyeres.2015.06.003 -
Nature Reviews. Neuroscience Jul 2014Müller glia are the major glial component of the retina. They are one of the last retinal cell types to be born during development, and they function to maintain... (Review)
Review
Müller glia are the major glial component of the retina. They are one of the last retinal cell types to be born during development, and they function to maintain retinal homeostasis and integrity. In mammals, Müller glia respond to retinal injury in various ways that can be either protective or detrimental to retinal function. Although these cells can be coaxed to proliferate and generate neurons under special circumstances, these responses are meagre and insufficient for repairing a damaged retina. By contrast, in teleost fish (such as zebrafish), the response of Müller glia to retinal injury involves a reprogramming event that imparts retinal stem cell characteristics and enables them to produce a proliferating population of progenitors that can regenerate all major retinal cell types and restore vision. Recent studies have revealed several important mechanisms underlying Müller glial cell reprogramming and retina regeneration in fish that may lead to new strategies for stimulating retina regeneration in mammals.
Topics: Animals; Ependymoglial Cells; Humans; Nerve Net; Nerve Regeneration; Neuroglia; Retina; Signal Transduction
PubMed: 24894585
DOI: 10.1038/nrn3723 -
Journal of Neuroinflammation Dec 2021Glaucoma, the leading cause of irreversible blindness, is a retinal neurodegenerative disease, which results from progressive apoptotic death of retinal ganglion cells...
BACKGROUND
Glaucoma, the leading cause of irreversible blindness, is a retinal neurodegenerative disease, which results from progressive apoptotic death of retinal ganglion cells (RGCs). Although the mechanisms underlying RGC apoptosis in glaucoma are extremely complicated, an abnormal cross-talk between retinal glial cells and RGCs is generally thought to be involved. However, how interaction of Müller cells and microglia, two types of glial cells, contributes to RGC injury is largely unknown.
METHODS
A mouse chronic ocular hypertension (COH) experimental glaucoma model was produced. Western blotting, immunofluorescence, quantitative real-time polymerase chain reaction (q-PCR), transwell co-culture of glial cells, flow cytometry assay, ELISA, Ca image, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) techniques were employed to investigate the interaction of Müller cells and microglia, and its underlying mechanisms in COH retina.
RESULTS
We first showed that Müller cell activation in mice with COH induced microglia activation through the ATP/P2X7 receptor pathway. The activation of microglia resulted in a significant increase in mRNA and protein levels of pro-inflammatory factors, such as tumor necrosis factor-α and interleukin-6. These inflammatory factors in turn caused the up-regulation of mRNA expression of pro-inflammatory factors in Müller cells through a positive feedback manner.
CONCLUSIONS
These findings provide robust evidence, for the first time, that retinal inflammatory response may be aggravated by an interplay between activated two types of glial cells. These results also suggest that to reduce the interplay between Müller cells and microglia could be a potential effective strategy for preventing the loss of RGCs in glaucoma.
Topics: Adenosine Triphosphate; Animals; Coculture Techniques; Cytokines; Ependymoglial Cells; Glaucoma; Macrophage Activation; Mice; Mice, Inbred C57BL; Microglia; Ocular Hypertension; Receptors, Purinergic P2X7; Retinal Ganglion Cells; Retinitis; Signal Transduction
PubMed: 34952606
DOI: 10.1186/s12974-021-02366-x -
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 -
Histology and Histopathology Sep 2017The circumventricular organs (CVOs) are midline structures located around the third and fourth ventricles that are characterized by a lack of blood-brain barrier. The... (Review)
Review
The circumventricular organs (CVOs) are midline structures located around the third and fourth ventricles that are characterized by a lack of blood-brain barrier. The pineal gland, median eminence, neurohypophysis and the subcommisural organ are classified as secretory, whereas the subfornical organ, area postrema and the organum vasculosum of the lamina terminalis as the sensory CVOs. Glial cells consisting of astrocytes and microglia/macrophages are present in all these organs. The pineal gland, neurohypophysis and the median eminence lack the presence of neurons that are present in the rest of the circumventricular organs. Most of the circumventricular organs are lined by ependymal cells except the pineal and the neurohypophysis. Modified ependymal cells known as tanycytes are present in the ependymal lining. These organs are important sites for communication with the cerebrospinal fluid as well as between the brain and peripheral organs via blood-borne products as they lack the blood brain barrier.
Topics: Animals; Blood-Brain Barrier; Circumventricular Organs; Ependyma; Ependymoglial Cells; Neuroglia
PubMed: 28177105
DOI: 10.14670/HH-11-881 -
Progress in Retinal and Eye Research Jan 2022Tractional deformations of the fovea mainly arise from an anomalous posterior vitreous detachment and contraction of epiretinal membranes, and also occur in eyes with... (Review)
Review
Tractional deformations of the fovea mainly arise from an anomalous posterior vitreous detachment and contraction of epiretinal membranes, and also occur in eyes with cystoid macular edema or high myopia. Traction to the fovea may cause partial- and full-thickness macular defects. Partial-thickness defects are foveal pseudocysts, macular pseudoholes, and tractional, degenerative, and outer lamellar holes. The morphology of the foveal defects can be partly explained by the shape of Müller cells and the location of tissue layer interfaces of low mechanical stability. Because Müller cells and astrocytes provide the structural scaffold of the fovea, they are active players in mediating tractional alterations of the fovea, in protecting the fovea from such alterations, and in the regeneration of the foveal structure. Tractional and degenerative lamellar holes are characterized by a disruption of the Müller cell cone in the foveola. After detachment or disruption of the cone, Müller cells of the foveal walls support the structural stability of the foveal center. After tractional elevation of the inner layers of the foveal walls, possibly resulting in foveoschisis, Müller cells transmit tractional forces from the inner to the outer retina leading to central photoreceptor layer defects and a detachment of the neuroretina from the retinal pigment epithelium. This mechanism plays a role in the widening of outer lameller and full-thickness macular holes, and contributes to visual impairment in eyes with macular disorders caused by conractile epiretinal membranes. Müller cells of the foveal walls may seal holes in the outer fovea and mediate the regeneration of the fovea after closure of full-thickness holes. The latter is mediated by the formation of temporary glial scars whereas persistent glial scars impede regular foveal regeneration. Further research is required to improve our understanding of the roles of glial cells in the pathogenesis and healing of tractional macular disorders.
Topics: Astrocytes; Ependymoglial Cells; Retrospective Studies; Tomography, Optical Coherence; Traction; Visual Acuity
PubMed: 34102317
DOI: 10.1016/j.preteyeres.2021.100977 -
Molecular Neurobiology May 2021Müller glia originate from neuroepithelium and are the principal glial cells in the retina. During retinal development, Müller glia are one of the last cell types to... (Review)
Review
Müller glia originate from neuroepithelium and are the principal glial cells in the retina. During retinal development, Müller glia are one of the last cell types to be born. In lower vertebrates, such as zebrafish, Müller glia possess a remarkable capacity for retinal regeneration following various forms of injury through a reprogramming process in which endogenous Müller glia proliferate and differentiate into all types of retinal cells. In mammals, Müller glia become reactive in response to damage to protect or to further impair retinal function. Although mammalian Müller glia have regenerative potential, it is limited as far as repairing damaged retina. Lessons learned from zebrafish will help reveal the critical mechanisms involved in Müller glia reprogramming. Progress has been made in triggering Müller glia to reprogram and generate functional neurons to restore vision in mammals indicating that Müller glia reprogramming may be a promising therapeutic strategy for human retinal diseases. This review comprehensively summarizes the mechanisms related to retinal regeneration in model animals and the critical advanced progress made in Müller glia reprogramming in mammals.
Topics: Animals; Cell Proliferation; Ependymoglial Cells; Nerve Regeneration; Retina; Zebrafish
PubMed: 33417229
DOI: 10.1007/s12035-020-02274-w -
Translational Research : the Journal of... May 2019Müller cells are the major glial cells spanning the entire layer of the retina and maintaining retinal structure. Under pathological conditions, Müller cells are... (Review)
Review
Müller cells are the major glial cells spanning the entire layer of the retina and maintaining retinal structure. Under pathological conditions, Müller cells are involved in retinal angiogenesis, a process of growing new blood vessels from pre-existing capillaries. In response to hypoxia, high glucose, and inflammation conditions, multiple signaling pathways are activated in Müller cells, followed by the increased production of proangiogenic factors including vascular endothelial growth factor, basic fibroblast growth factor, matrix metalloproteinases, Netrin-4, and angiopoietin-like 4. Expression of antiangiogenic factors is also downregulated in Müller cells. Besides, proliferation and dedifferentiation of Müller cells facilitates retinal angiogenesis. In this review, we summarized molecular mechanisms of Müller cells-related retinal angiogenesis. The potential of Müller cells as a therapeutic target for retinal angiogenesis was also discussed.
Topics: Animals; Cell Dedifferentiation; Ependymoglial Cells; Humans; Hypoxia; Inflammation; Models, Biological; Retinal Neovascularization
PubMed: 30639368
DOI: 10.1016/j.trsl.2018.12.006 -
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