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Muller glial cells ensheath all retinal neurons in vertebrate retinae. There are a multitude of functional interactions between neurons and Muller cells, including delivery of the light stimuli to the photoreceptor cells in the inverted vertebrate retina, a 'metabolic symbiosis' with the neurons, and the processing of visual information. Muller cells are also responsible for the maintenance of the homeostasis of the retinal extracellular milieu (ions, water, neuro-transmitter molecules, and pH). In vascularized retinae, Muller cells may also be involved in the control of angiogenesis, and the regulation of retinal blood flow. Virtually every disease of the retina is associated with a reactive Muller cell gliosis which, on the one hand, supports the survival of retinal neurons but, on the other hand, may accelerate the progress of neuronal degeneration: Muller cells protect neurons via a release of neurotrophic factors. However, gliotic Muller cells display a dysregulation of various neuron-supportive functions. This contributes to a disturbance of retinal glutamate metabolism and ion homeostasis, and causes the development of retinal edema and neuronal cell death. Moreover, there are diseases evoking a primary Muller cell insufficiency, such as hepatic retinopathy and certain forms of glaucoma. Any impairment of supportive functions of Muller cells, primary or secondary, must cause and/or aggravate a dysfunction and loss of neurons, by increasing the susceptibility of neurons to stressful stimuli in the diseased retina. Muller cells may be used in the future for novel therapeutic strategies to protect neurons against apoptosis (i.e. somatic gene therapy), or to differentiate retinal neurons from Muller/stem cells. Meanwhile, a proper understanding of the gliotic responses of Muller cells in the diseased retina, and of their protective vs. detrimental effects, is essential for the development of efficient therapeutic strategies that use and stimulate the neuron-supportive/-protective - and prevent the destructive - mechanisms of gliosis.
Muller cells may be used in the future for novel therapeutic strategies to protect neurons against apoptosis (for example, somatic gene therapy), or to differentiate retinal neurons from Muller/stem cells. Meanwhile, a proper understanding of the gliotic responses of Muller cells in the diseased retina, and of their protective vs. detrimental effects, is essential for the development of efficient therapeutic strategies that use and stimulate the neuron-supportive/-protective - and prevent the destructive - mechanisms of gliosis.
The Fovea: Structure, Function, Development, and Disease summarizes the current biological knowledge regarding the two types of the vertebrate fovea (and its main structural elements, the Muller cells). This information is then used to explain different aspects of human vision, foveal development, and macular disorders. Sections give an overview of the retinal structure and the different types of retinal glia, survey the structure and function of the primate and non-mammalian fovea types, discuss foveal development-with a focus on the human fovea, cover the roles of Muller cells and astrocytes in the pathogenesis and regeneration of various human macular disorders are described. Using a translational approach, this reference is a valuable text for scientists, clinicians and physicians interested in the fovea. Readers will gain a new understanding of the cellular basics of the fovea, which is the most important part of the eye.
In 1851, Heinrich Muller discovered what he called "radial fibers" and what we now call Muller cells, as the principal glial cells of the vertebrate retina. Later on, other glial cell types were found in the retina, including astrocytes, microglia, and even oligodendrocytes. It turned out that retinal glial cells are essential constituents of the tissue. For instance, Muller cells appear to constitute the "core" of columnar units of clonally and functionally related groups of neurons. Their primary function is to support neuronal functioning by guiding the light towards the photoreceptor cells, removing excess neurotransmitter molecules from extracellular space, and performing efficient clearance of excess extracellular potassium ions. The latter two functions are also crucial for neuronal survival and are coupled to water clearance which is also essential. Muller cells are capable of "sensing" neuronal activity and modifying it by the release of signal substances (gliotransmitters). In cases of retinal injuries the Muller cells become reactive, and all above-mentioned functions are impaired. However, such de-differentiated Muller cells may proliferate, and may even serve as stem cells for the regeneration of a damaged retina. As well as the Muller cells, retinal astrocytes and microglial cells are important players in retinal development and function. This book gives a comprehensive survey of the present knowledge on retinal glia.
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