Müller glia, or Müller cells, are a type of retinal

glial cell Glia, also called glial cells (gliocytes) or neuroglia, are non-neuronal cells in the central nervous system (the brain and the spinal cord) and in the peripheral nervous system that do not produce electrical impulses. The neuroglia make up ...

s, first recognized and described by Heinrich Müller. They are found in the

vertebrate Vertebrates () are animals with a vertebral column (backbone or spine), and a cranium, or skull. The vertebral column surrounds and protects the spinal cord, while the cranium protects the brain. The vertebrates make up the subphylum Vertebra ...

retina The retina (; or retinas) is the innermost, photosensitivity, light-sensitive layer of tissue (biology), tissue of the eye of most vertebrates and some Mollusca, molluscs. The optics of the eye create a focus (optics), focused two-dimensional ...

, where they serve as support cells for the neurons, as all glial cells do. They are the most common type of glial cell found in the retina. While their cell bodies are located in the inner nuclear layer of the retina, they span across the entire retina. The major role of the Müller cells is to maintain the structural and functional stability of retinal cells. This includes regulation of the extracellular environment via uptake of

neurotransmitters A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotransmitters are rele ...

, removal of debris, regulation of K⁺ levels, storage of

glycogen Glycogen is a multibranched polysaccharide of glucose that serves as a form of energy storage in animals, fungi, and bacteria. It is the main storage form of glucose in the human body. Glycogen functions as one of three regularly used forms ...

, electrical insulation of receptors and other neurons, and mechanical support of the neural retina.

Development

Müller glia are derived developmentally from two distinct populations of cells. The Müller glia cell is the only retinal glial cell that shares a common

cell lineage Cell lineage denotes the developmental history of a tissue or organ from the fertilized egg. This is based on the tracking of an organism's cellular ancestry due to the cell divisions and relocation as time progresses. This starts with the origina ...

with retinal neurons. A subset of Müller glia has been shown to originate from

neural crest The neural crest is a ridge-like structure that is formed transiently between the epidermal ectoderm and neural plate during vertebrate development. Neural crest cells originate from this structure through the epithelial-mesenchymal transition, ...

cells. They are shown to be critical to the development of the retina in mice, serving as promoters of retinal growth and

histogenesis Histogenesis is the formation of different tissues from undifferentiated cells. These cells are constituents of three primary germ layers, the endoderm, mesoderm, and ectoderm. The science of the microscopic structures of the tissues formed within ...

, via a nonspecific

esterase In biochemistry, an esterase is a class of enzyme that splits esters into an acid and an alcohol in a chemical reaction with water called hydrolysis (and as such, it is a type of hydrolase). A wide range of different esterases exist that differ ...

-mediated mechanism. Müller glia have also been implicated as

guidepost cells Guidepost cells are cells which assist in the subcellular organization of both neural axon growth and migration. They act as intermediate targets for long and complex axonal growths by creating short and easy pathways, leading axon growth cones t ...

for the developing

axon An axon (from Greek ἄξων ''áxōn'', axis) or nerve fiber (or nerve fibre: see American and British English spelling differences#-re, -er, spelling differences) is a long, slender cellular extensions, projection of a nerve cell, or neuron, ...

s of neurons in the chick retina. Studies using a zebrafish model of

Usher syndrome Usher syndrome, also known as Hallgren syndrome, Usher–Hallgren syndrome, retinitis pigmentosa–dysacusis syndrome or dystrophia retinae dysacusis syndrome, is a rare genetic disorder caused by a mutation in any one of at least 11 genes result ...

have implicated a role for Müller glia in

synaptogenesis Synaptogenesis is the formation of synapses between neurons in the nervous system. Although it occurs throughout a healthy person's lifespan, an explosion of synapse formation occurs during early brain development, known as exuberant synaptogene ...

, the formation of

synapse In the nervous system, a synapse is a structure that allows a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or a target effector cell. Synapses can be classified as either chemical or electrical, depending o ...

Neuronal support

As glial cells, Müller glia serve a secondary but important role to

neuron A neuron (American English), neurone (British English), or nerve cell, is an membrane potential#Cell excitability, excitable cell (biology), cell that fires electric signals called action potentials across a neural network (biology), neural net ...

s. As such, they have been shown to serve as important mediators of

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...

(

acetylcholine Acetylcholine (ACh) is an organic compound that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Par ...

and

GABA GABA (gamma-aminobutyric acid, γ-aminobutyric acid) is the chief inhibitory neurotransmitter in the developmentally mature mammalian central nervous system. Its principal role is reducing neuronal excitability throughout the nervous system. GA ...

specifically) degradation and maintenance of a favorable retinal microenvironment in turtles. Müller glia have also been shown to be important in the induction of the enzyme

glutamine synthetase Glutamine synthetase (GS) () is an enzyme that catalyzes the condensation of glutamate and ammonia to form glutamine: Glutamate + ATP + NH3 → Glutamine + ADP + phosphate Glutamine synthetase uses ammonia produced by nitrate reduction ...

in chicken embryos, which is an important actor in the regulation of glutamine and ammonia concentrations in the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...

. Müller glia have been further identified as fundamental to the transmission of light through the vertebrate retina due to their unique funnel shape, orientation within the retina and more favorable physical properties.

Role in retinal regeneration

Müller glia are currently being studied for their role in neural regeneration, a phenomenon which is not known to occur in humans. Studies of the regenerative properties of Müller glia in both the

zebrafish The zebrafish (''Danio rerio'') is a species of freshwater ray-finned fish belonging to the family Danionidae of the order Cypriniformes. Native to South Asia, it is a popular aquarium fish, frequently sold under the trade name zebra danio (an ...

and the chicken retina have been performed, with the exact molecular mechanism of regeneration remaining unclear. Further studies performed in mice have shown that overexpression of

Ascl1 Achaete-scute homolog 1 is a protein that in humans is encoded by the ''ASCL1'' gene. Because it was discovered subsequent to studies on its homolog in Drosophila, the Achaete-scute complex, it was originally named MASH-1 for mammalian achaete s ...

in Müller glia in conjunction with administration of a

histone deacetylase inhibitor Histone deacetylase inhibitors (HDAC inhibitors, HDACi, HDIs) are chemical compounds that enzyme inhibitor, inhibit histone deacetylases. Since acetylation of histones, deacetylation of histones produces transcriptionally silenced heterochromatin ...

allowed for regeneration of retinal neurons from Müller glia. Studies in human models have demonstrated that Müller glia has the potential to serve as

stem cell In multicellular organisms, stem cells are undifferentiated or partially differentiated cells that can change into various types of cells and proliferate indefinitely to produce more of the same stem cell. They are the earliest type of cell ...

s in the adult retina and are efficient rod photoreceptor progenitors. Damage to retinal cells induces Müller cells to produce

gliosis Gliosis is a nonspecific reactive change of glial cells in response to damage to the central nervous system (CNS). In most cases, gliosis involves the proliferation or hypertrophy of several different types of glial cells, including astrocytes ...

. The result of the response varies depending on the damage and the organism in which this damage occurs. It has been shown in

and mice that Müller glia undergo

dedifferentiation Dedifferentiation (pronounced dē-ˌdi-fə-ˌren-chē-ˈā-shən) is a transient process by which cells become less specialized and return to an earlier cell state within the same lineage. This suggests an increase in cell potency, meaning that, f ...

into

multipotent Cell potency is a cell's ability to differentiate into other cell types. The more cell types a cell can differentiate into, the greater its potency. Potency is also described as the gene activation potential within a cell, which like a continuum ...

progenitor cell A progenitor cell is a biological cell that can differentiate into a specific cell type. Stem cells and progenitor cells have this ability in common. However, stem cells are less specified than progenitor cells. Progenitor cells can only diffe ...

s. The progenitor cell can then divide and differentiate into a number of retinal cell types, including

photoreceptor cell A photoreceptor cell is a specialized type of neuroepithelial cell found in the retina that is capable of visual phototransduction. The great biological importance of photoreceptors is that they convert light (visible electromagnetic radiation ...

s, that may have been damaged during injury. Further research has shown that Müller glia can act as light collectors in the

mammal A mammal () is a vertebrate animal of the Class (biology), class Mammalia (). Mammals are characterised by the presence of milk-producing mammary glands for feeding their young, a broad neocortex region of the brain, fur or hair, and three ...

ian eye, analogous to the

fiber optic An optical fiber, or optical fibre, is a flexible glass or plastic fiber that can transmit light from one end to the other. Such fibers find wide usage in fiber-optic communications, where they permit transmission over longer distances and at ...

plate, funneling light to the rod and

cone In geometry, a cone is a three-dimensional figure that tapers smoothly from a flat base (typically a circle) to a point not contained in the base, called the '' apex'' or '' vertex''. A cone is formed by a set of line segments, half-lines ...

photoreceptors. *

References

External links

New Hope For Regenerating Damaged Human Retina: Sleeping Stem Cells Successfully Awakened

Müller cells
at Virginia-Maryland Regional College of Veterinary Medicine *
NIF Search - Muller Cell
via the

Neuroscience Information Framework The Neuroscience Information Framework is a repository of global neuroscience web resources, including experimental, clinical, and translational neuroscience databases, knowledge bases, atlases, and genetic/ genomic resources and provides many aut ...

{{Eye anatomy Cells Articles containing video clips

Development

Neuronal support

Role in retinal regeneration

See also

References

External links