What do retinal Müller (glial) cells do for their neuronal ‘small siblings’?

doi:10.1016/0891-0618(93)90042-3

Journal of Chemical Neuroanatomy

Volume 6, Issue 4, July–August 1993, Pages 201-213

https://doi.org/10.1016/0891-0618(93)90042-3 Get rights and content

Abstract

Müller (radial glial) cells are the predominant glia of the vertebrate retina. They arise, together with rod photoreceptor cells, bipolar cells, and a subset of amacrine cells, from common precursor cells during a late proliferative phase. One Müller cell and a species-specific number of such neurons seem to form a columnar unit within the retinal tissue. In contrast, ‘extracolumnar neurons’ (ganglion cells, cone photoreceptor cells, horizontal cells, and another subset of amacrine cells) are born and start differentiation before most Müller cells are generated. It may be essential for such neurons to develop metabolic capacities sufficient to support their own survival, whereas late-born (‘columnar’) neurons seem to depend on a nursing function of their ‘sisterly’ Müller cell. Thus, out of the cell types within a retinal column it is exclusively the Müller cell that possesses the enzymes for glycogen metabolism.

We present evidence that Müller cells express functional insulin receptors. Furthermore, isolated Müller cells rapidly hydrolyse glycogen when they are exposed to an elevated extracellular K⁺ion concentration, a signal that is involved in the regulation of neuronal-glial metabolic cooperation in the brain. Müller cells are also thought to be essential for rapid and effective retinal K⁺ homeostasis. We present patch-clamp measurements on Müller cells of various vertebrate species that all demonstrate inwardly rectifying K⁺ channels; this type of channel is well-suited to mediate spatial buffering currents. A mathematical model is presented that allows estimation of Müller cell-mediated K⁺ currents. A simulation analysis shows that these currents greatly limit lateral spread of excitation beyond the borders of light-stimulated retinal columns, and thus help to maintain visual acuity.

References (128)

G.S. Bennett et al.
Transient expression of a neurofilament protein by replicating neuroepithelial cells of the embryonic chick brain
Dev. Biol.
(1985)
D.W. Clarke et al.
Insulin binds to specific receptors and stimulates 2-deoxy-D-glucose uptake in cultured glial cells from rat brain
J. Biol. Chem.
(1984)
W. Eberhardt et al.
Spatial buffering of potassium by retinal Müller (glial) cells of various morphologies calculated by a model
Neuroscience
(1987)
B. Ehinger et al.
Autoradiography of some suspected neurotransmitter substances: GABA, glycine, glutamic acid, histamine, dopamine and F5L-DOPA
Brain Res.
(1971)
A.M. Harman et al.
Generation of retinal cells in the wallaby
Setonix brachyurus (quokka)
Neuroscience
(1989)
L. Hertz et al.
Effects of monoamine transmitters on neurons and astrocytes: correlation between energy metabolism and intracellular messengers
Prog. Brain Res.
(1992)
J.W. Hinds et al.
Early ganglion cell differentiation in the mouse retina: an electron microscopic analysis utilizing serial sections
Dev. Biol.
(1974)
C.E. Holt et al.
Cellular determination in the Xenopus retina is independent of lineage and birth date
Neuron
(1988)
T.S. Kern et al.
Distribution of aldose reductase in ocular tissues
Exp. Eye Res.
(1981)
P.J. Linser et al.
Cellular compartmentalization of carbonic anhydrase-C and glutamine synthetase in developing and mature mouse neural retina
Dev. Brain Res.
(1984)

S.C. Massey

Cell types using glutamate as a neurotransmitter in the vertebrate retina

Prog. Ret. Res.

(1990)

M. Murakami et al.

Effects of aspartate and glutamate on the bipolar cells in the carp retina

Vision Res.

(1975)

G.L. Musser et al.

Localization of carbonic anhydrase activity in the vertebrate retina

Exp. Eye Res.

(1973)

J.R. Naegele et al.

A carbohydrate epitope defined by monoclonal antibody VC1.1 is found on N-CAM and other cell adhesion molecules

Brain Res.

(1991)

E.A. Newman

The Müller cell

T. Okumura et al.

Effect of prostaglandins and their analogues on hormone-stimulated glycogenolysis in primary cultures of rat hepatocytes

Biochim. Biophys. Acta

(1988)

C. Poitry-Yamate et al.

Glial (Müller) cells take up and phosphorylate [³H]2-deoxy-F5D-glucose in a mammalian retina

Neurosci, Lett.

(1991)

P.A. Raymond et al.

Germinal cells in the goldfish retina that produce rod photoreceptors

Dev. Biol.

(1987)

B.E. Reese et al.

Neurogenesis in the retinal ganglion cell layer of the rat

Neuroscience

(1992)

W. Reichelt et al.

Potassium as a signal for both proliferation and differentiation of rabbit retinal (Müller) glia growing in cell culture

Cell. Signalling

(1989)

H. Ripps et al.

Neuron-glia interaction in the brain and retina

Y. Akagi et al.

Localization of aldose reductase in the human eye

Diabetes

(1984)

S. Allodi et al.

Genesis of neurons in the retinal ganglion cell layer in the opossum

Anat. Embryol.

(1992)

D. Altshuler et al.

Specification of cell type in the vertebrate retina

A. Ames

Energy requirements of CNS cells as related to their function and to their vulnerability to ischemia: a commentary based on studies of retina

Can. J. Physiol. Pharmacol.

(1992)

A. Ames et al.

Energy requirements of glutamatergic pathways in retina

J. Neurosci.

(1992)

J.C. Blanks et al.

An autoradiographic analysis of postnatal cell proliferation in the normal and degenerative mouse retina

J. Comp. Neurol.

(1977)

S.A. Bloomfield et al.

Roles of aspartate and glutamate in synaptic transmission in rabbit retina. I. Outer plexiform layer

J. Neurophysiol.

(1985)

L. Bonfanti et al.

Distribution of protein gene product 9.5 (PGP 9.5) in the vertebrate retina: evidence that immunoreactivity is restricted to mammalian horizontal and ganglion cells

J. Comp. Neurol.

(1992)

H. Brew et al.

Electrogenic glutamate uptake is a major current carrier in the membrane of axolotl retinal glial cells

Nature (Lond.)

(1987)

H. Brew et al.

Endfeet of retinal glial cells have higher densities of ion channels that mediate K⁺ buffering

Nature

(1986)

M. Cambray-Deakin et al.

Effects of neurotransmitters on astrocyte glycogen stores in vitro

J. Neurochem.

(1988)

V. Canzec et al.

In vivo release of glutamate and aspartate following optic nerve stimulation

Nature

(1981)

L.D. Carter-Dawson et al.

Rods and cones in the mouse retina. II. Autoradiographic analysis of cell generation using tritiated thymidine

J. Comp. Neurol.

(1979)

T.I. Chao et al.

Voltage-dependent K⁺ channels in Müller (glial) cells of the rabbit retina and their possible contributions to K⁺ clearance and cell proliferation

Pflügers Arch.

(1993)

J.D. Conner et al.

Ionic and electrophysiological properties of retinal Müller (glial) cells of the turtle

J. Physiol.

(1985)

J.L. Craft et al.

Development of the outer plexiform layer in albino rats

Curr. Eye Res.

(1983)

A. Das et al.

Demonstration of insulin-specific mRNA in cultured rat retinal glial cells

Invest. Ophthalmol. Vis. Sci.

(1987)

A. Das et al.

Immunocytochemistry of mouse and human retina with antisera to insulin and S-100 protein

Curr. Eye Res.

(1984)

R. Dringen

Untersuchungen zur Funktion und Regulation des Glycogens in den Astrogliazellen des Gehirns

D. Eichner et al.

Zur Frage des Netzhautglykogens beim Meerschweinchen

Z. Zellforsch.

(1962)

S.C. Fields-Berry et al.

A recombinant retrovirus encoding alkaline phosphatase confirms clonal boundary assignment in lineage analysis of murine retina

R. Gábriel et al.

Microtubule-associated protein 2 (MAP2)-immunoreactive neurons in the retina of Bufo marinus: colocalisation with tyrosine hydroxylase and serotonin in amacrine cells

Cell Tiss. Res.

(1992)

A.R. Gardner-Medwin

Analysis of potassium dynamics in mammalian brain tissue

J. Physiol. (London.)

(1983)

O.P. Hamill et al.

Improved patch-clamp technique for high resolution current recording from cells and cell-free membrane patches

Pflügers Arch.

(1981)

L. Hertz

Metabolic interactions between neurons and astrocytes

L. Hertz et al.

Energy metabolism at the cellular level of the CNS

Can. J. Physiol. Pharmacol.

(1992)

L. Hertz et al.

Neuronal-astrocytic interactions in metabolism of transmitter amino acids of glutamate family

L. Hertz et al.

Energyions-water in brain cells: A synopsis of interrelations

Can J. Physiol. Pharmacol.

(1992)

J.W. Hinds et al.

Differentiation of photoreceptors and horizontal cells in the embryonic mouse retina: an electron microscopic, serial section analysis

J. Comp. Neurol.

(1979)

Cited by (159)

Expression of two major isoforms of MYO7A in the retina: Considerations for gene therapy of Usher syndrome type 1B
2023, Vision Research
Usher syndrome type 1B (USH1B) is a deaf-blindness disorder, caused by mutations in the MYO7A gene, which encodes the heavy chain of an unconventional actin-based motor protein. Here, we examined the two retinal isoforms of MYO7A, IF1 and IF2. We compared 3D models of the two isoforms and noted that the 38-amino acid region that is present in IF1 but absent from IF2 affects the C lobe of the FERM1 domain and the opening of a cleft in this potentially important protein binding domain. Expression of each of the two isoforms of human MYO7A and pig and mouse Myo7a was detected in the RPE and neural retina. Quantification by qPCR showed that the expression of IF2 was typically ∼ 7-fold greater than that of IF1. We discuss the implications of these findings for any USH1B gene therapy strategy. Given the current incomplete knowledge of the functions of each isoform, both isoforms should be considered for targeting both the RPE and the neural retina in gene augmentation therapies.
Retinal dystrophins and the retinopathy of Duchenne muscular dystrophy
2023, Progress in Retinal and Eye Research
Duchenne muscular dystrophy (DMD) is caused by X-linked inherited or de novo DMD gene mutations predominantly affecting males who develop early-onset muscle degeneration, severely affecting their quality of life and leading to reduced life expectancy. DMD patients may also develop proliferative retinopathy, cataract, ERG abnormalities, altered contrast sensitivity, color vision losses, and elevated flash detection thresholds during dark adaptation. Depending on the position of the genetic alteration in the large DMD gene, it is associated with a lack of the full-length dystrophin protein possibly with an additional loss of one or several other dystrophins, which are normally transcribed from internal promoters in retina and crystalline lens. During the last decades, the properties of the dystrophins have been characterized in patients with different genetic alterations and in genetic mouse models of DMD. The complex expression pattern of the dystrophins in photoreceptors, Müller glial cells and astrocytes, likely influences synaptic transmission, ionic balance and vascular integrity of the retina. However, the specific function of each retinal dystrophin remains largely unknown. This review describes the current knowledge on dystrophin expression, the putative molecular, structural, and physiological properties of retinal dystrophins, and the main clinical implications associated with the loss of dystrophins in DMD patients and mouse models. Current data and working hypotheses warrant future research on retinal dystrophins to increase our understanding of dystrophin function in the central nervous system in general and to unveil new retinal mechanisms and therapeutic avenues for retinal diseases.
A tridomain model for potassium clearance in optic nerve of Necturus
2021, Biophysical Journal
Complex fluids flow in complex ways in complex structures. Transport of water and various organic and inorganic molecules in the central nervous system are important in a wide range of biological and medical processes. However, the exact driving mechanisms are often not known. In this work, we investigate flows induced by action potentials in an optic nerve as a prototype of the central nervous system. Different from traditional fluid dynamics problems, flows in biological tissues such as the central nervous system are coupled with ion transport. They are driven by osmosis created by concentration gradient of ionic solutions, which in turn influence the transport of ions. Our mathematical model is based on the known structural and biophysical properties of the experimental system used by the Harvard group Orkand et al. Asymptotic analysis and numerical computation show the significant role of water in convective ion transport. The full model (including water) and the electrodiffusion model (excluding water) are compared in detail to reveal an interesting interplay between water and ion transport. In the full model, convection due to water flow dominates inside the glial domain. This water flow in the glia contributes significantly to the spatial buffering of potassium in the extracellular space. Convection in the extracellular domain does not contribute significantly to spatial buffering. Electrodiffusion is the dominant mechanism for flows confined to the extracellular domain.
The Fovea: Structure, Function, Development, and Tractional Disorders
2021, The Fovea: Structure, Function, Development, and Tractional Disorders
Comparative Anatomy of Glial Cells in Mammals
2020, Evolutionary Neuroscience
Neuron-supporting glial cells display a considerable variability in phenotype and function. The first part of the chapter describes general principles of glial cell phenotype and distribution including evolution of glia-mediated neuronal support, glial morphology according to the types of cell processes, glial morphology in development, and glioneuronal domains of information processing at various hierarchical levels. The second part describes in more detail the various phenotypes and functions of glial cells in the mammalian central and peripheral nervous systems.
Retinal structure and function in monkeys with fetal alcohol exposure
2018, Experimental Eye Research
Citation Excerpt :
Our results confirm that hypothesis by showing alcohol-associated increases in astrocytic hypertrophy in the retina of vervet monkeys. Here, we propose that the functional changes observed in the FAE retina are not due to abnormal retinal cell distribution (Harrar et al., 2017), but rather to the increase of astrocytes that induce a higher potassium buffering (Reichenbach et al., 1993; Walz, 2000). This assumption is supported by our results that showed an increased photopic flicker ERG amplitudes in FAE monkeys.
Exposure to ethanol in utero leads to several brain development disorders including retinal abnormalities whose underlying cellular pathogenesis remains elusive. We recently reported that fetal alcohol exposure (FAE) in vervet monkeys induces anomalies of full-field electroretinogram (ERG) waveforms that suggest premature aging of the retina. The goal of this study is to characterize the anatomo-functional mechanisms underlying the retinal changes observed in fetal alcohol exposed (FAE) monkeys, and age- and sex-matched normals. First, we examined in vivo the fundus of the eyes, measured intraocular pressure (IOP) and assessed cone activity using flicker ERG. Second, we investigated ex vivo, protein expression and anatomical organization of the retina using Western blotting, classical histology and immunohistochemistry. Our results indicated that the fundus of the eyes showed both, increased vascularization (tessellated fundus) and IOP in FAE monkeys. Furthermore, light-adapted flicker responses above 15 Hz were also significantly higher in FAE monkeys. Although there were no obvious changes in the overall anatomy in the FAE retina, Glial Fibrillary Acidic Protein (GFAP, a potent marker of astrocytes) immunoreactivity was increased in the FAE retinal ganglion cell layer indicating a strong astrogliosis. These alterations were present in juvenile (2 years old) monkeys and persist in adults (8 years old). Moreover, using specific cell type markers, no significant modifications in the morphology of the photoreceptors, horizontal cells, bipolar cells, and amacrine cells were observed. Our data indicate that FAE does indeed induce anatomical changes within the retinal ganglion cell layer that are reflected in the increased photosensitivity of the cone photoreceptors.

View all citing articles on Scopus

View full text

What do retinal Müller (glial) cells do for their neuronal ‘small siblings’?

Abstract

Dev. Biol.

J. Biol. Chem.

Neuroscience

Brain Res.

Neuroscience

Prog. Brain Res.

Dev. Biol.

Neuron

Exp. Eye Res.

Dev. Brain Res.

Prog. Ret. Res.

Vision Res.

Exp. Eye Res.

Brain Res.

Biochim. Biophys. Acta

Neurosci, Lett.

Dev. Biol.

Neuroscience

Cell. Signalling

Localization of aldose reductase in the human eye

Diabetes

Genesis of neurons in the retinal ganglion cell layer in the opossum

Anat. Embryol.

Specification of cell type in the vertebrate retina

Energy requirements of CNS cells as related to their function and to their vulnerability to ischemia: a commentary based on studies of retina

Can. J. Physiol. Pharmacol.

Energy requirements of glutamatergic pathways in retina

J. Neurosci.

An autoradiographic analysis of postnatal cell proliferation in the normal and degenerative mouse retina

J. Comp. Neurol.

Roles of aspartate and glutamate in synaptic transmission in rabbit retina. I. Outer plexiform layer

J. Neurophysiol.

Distribution of protein gene product 9.5 (PGP 9.5) in the vertebrate retina: evidence that immunoreactivity is restricted to mammalian horizontal and ganglion cells

J. Comp. Neurol.

Electrogenic glutamate uptake is a major current carrier in the membrane of axolotl retinal glial cells

Nature (Lond.)

Endfeet of retinal glial cells have higher densities of ion channels that mediate K+ buffering

Nature

Effects of neurotransmitters on astrocyte glycogen stores in vitro

J. Neurochem.

In vivo release of glutamate and aspartate following optic nerve stimulation

Nature

Rods and cones in the mouse retina. II. Autoradiographic analysis of cell generation using tritiated thymidine

J. Comp. Neurol.

Voltage-dependent K+ channels in Müller (glial) cells of the rabbit retina and their possible contributions to K+ clearance and cell proliferation

Pflügers Arch.

Ionic and electrophysiological properties of retinal Müller (glial) cells of the turtle

J. Physiol.

Development of the outer plexiform layer in albino rats

Curr. Eye Res.

Demonstration of insulin-specific mRNA in cultured rat retinal glial cells

Invest. Ophthalmol. Vis. Sci.

Immunocytochemistry of mouse and human retina with antisera to insulin and S-100 protein

Curr. Eye Res.

Untersuchungen zur Funktion und Regulation des Glycogens in den Astrogliazellen des Gehirns

Zur Frage des Netzhautglykogens beim Meerschweinchen

Z. Zellforsch.

A recombinant retrovirus encoding alkaline phosphatase confirms clonal boundary assignment in lineage analysis of murine retina

Microtubule-associated protein 2 (MAP2)-immunoreactive neurons in the retina of Bufo marinus: colocalisation with tyrosine hydroxylase and serotonin in amacrine cells

Cell Tiss. Res.

Analysis of potassium dynamics in mammalian brain tissue

J. Physiol. (London.)

Improved patch-clamp technique for high resolution current recording from cells and cell-free membrane patches

Pflügers Arch.

Metabolic interactions between neurons and astrocytes

Energy metabolism at the cellular level of the CNS

Can. J. Physiol. Pharmacol.

Neuronal-astrocytic interactions in metabolism of transmitter amino acids of glutamate family

Energyions-water in brain cells: A synopsis of interrelations

Can J. Physiol. Pharmacol.

Differentiation of photoreceptors and horizontal cells in the embryonic mouse retina: an electron microscopic, serial section analysis

J. Comp. Neurol.

Endfeet of retinal glial cells have higher densities of ion channels that mediate K⁺ buffering

Voltage-dependent K⁺ channels in Müller (glial) cells of the rabbit retina and their possible contributions to K⁺ clearance and cell proliferation