Muller Cells in the Healthy and Diseased Retina (eBook)

Andreas Bringmann, Andreas Reichenbach (Autoren)

eBook Download: PDF

2010 | 2010
XIV, 417 Seiten
Springer New York (Verlag)
978-1-4419-1672-3 (ISBN)

Infos

Müller 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 Müller/stem cells. Meanwhile, a proper understanding of the gliotic responses of Müller 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.

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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.

Inhalt

Acknowledgments 5
Contents 7
Abbreviations 10
1 Introduction 14
1.1 Glial Cells the Second Cellular Element of Neural Tissue 14
1.1.1 Definition, Origin, and Functional Role(s) of Glia 14
1.1.2 Basic Structural and Ultrastructural Features of Glia in Vertebrate CNS 20
1.1.3 A hierarchy of Neuronal/Glial/Vascular Domains in the CNS 24
1.2 The Vertebrate Retina as a Part of the CNS 28
1.2.1 Some Phylogenetic and Ontogenetic Basics 28
1.2.2 Some Basics of Retinal Stimulus Perception and Information Processing 34
1.2.3 Blood Vessels and Glia: A Basis for Nutrition, Waste Management and Inflammation 39
2 Müller Cells in the Healthy Retina 47
2.1 Morphology and Cellular Properties of Mller Cells as Constituents of Retinal Tissue 47
2.1.1 Basic Morphology of Müller Cells 47
2.1.2 Topographical Adaptations 52
2.1.3 Müller Cells in the Primate Fovea Centralis 53
2.1.4 Ultrastructure of Müller Cells 57
2.1.5 Müller Cell Markers 65
2.1.6 Intermediate Filaments 68
2.1.7 Junctional Cell Coupling 69
2.2 Retinal Columnar Units and Domains Role(s) of Mller Cells in Retina Organization 70
2.2.1 The M''ller Cell Population Forms a Regular but Locally Variable ''Scaffold'' 70
2.2.2 Repetitive Retinal Columnar Units and Their Diversity Among Vertebrate Retina Types 72
2.2.3 A Hierarchy of Retinal Domains 78
2.2.4 Retina Development I: Cell Proliferation, Progenitor Cells, and Radial Glia 78
2.2.5 Retina Development II: Cell Differentiation and Migration -- Layers and Mosaics 84
2.2.6 Retina Development III: Late Shaping Processes -- Retina Expansion and Foveation 87
2.2.7 Functional Maturation of Efficient Glia-Neuron Interactions in the Retina 97
2.3 Stimulus (Light) Transport to the Photoreceptor Cells A Role for Mller Cells 100
2.3.1 Optical Properties of the Vertebrate Retina 100
2.3.2 Individual Müller Cells Are Light-Guiding Fibers 101
2.3.3 The M''ller Cell Population Constitutes a Versatile ''Fiberoptic Plate'' 103
2.3.4 A Possible Contribution of Rod Cell Nuclear ''Chains'' in the ONL 106
2.3.5 And What About the Optics of the Fovea(s)? 108
2.4 Mller Cells Are Endowed with Tools to Control the Neuronal Microenvironment 110
2.4.1 Carriers, Transporters, and Enzymes: Neurotransmitter Recycling 110
2.4.1.1 Glutamate Removal and Metabolism 111
2.4.1.2 Glutamate Removal 111
2.4.1.3 Removal of NAAG 120
2.4.1.4 Glutamate Metabolism -- Production of Glutamine 120
2.4.1.5 GABA Uptake and Metabolism 127
2.4.1.6 Uptake of Glycine and D-Serine 129
2.4.1.7 Uptake of Dopamine/Serotonin 130
2.4.1.8 Uptake of Cannabinoids 131
2.4.1.9 Degradation of Purinergic Receptor Agonists 131
2.4.2 Potassium Channels of Müller Cells: Retinal Potassium Homeostasis 132
2.4.2.1 Kir Channels 136
2.4.2.2 BK Channels 149
2.4.2.3 K A Currents 156
2.4.2.4 Other Potassium Channels in Müller Cells 157
2.4.3 Potassium and Water Channels: Retinal Water Homeostasis 157
2.4.3.1 Water Fluxes Through the Retina 157
2.4.3.2 Aquaporins in the Retina 159
2.4.3.3 Glutamate-Evoked Swelling of Retinal Neurons 160
2.4.3.4 Disturbance of the Water Homeostasis Under Pathological Conditions 162
2.4.3.5 Regulation of Aquaporin-4 and Kir4.1 166
2.4.3.6 Decrease in Osmotic Müller Cell Swelling During Ontogenetic Development 167
2.4.3.7 Mechanisms of Osmotic Müller Cell Swelling 168
2.4.4 Regulation of M--ller Cell Volume -- Retinal Volume Homeostasis 170
2.4.5 Contribution(s) of Other Ion Channels 173
2.4.5.1 Voltage-Dependent Calcium Channels 173
2.4.5.2 Voltage-Dependent Sodium Channels 177
2.4.5.3 Epithelial Sodium Channels 179
2.4.5.4 Cation Channels 179
2.4.5.5 Chloride Channels 180
2.5 Retina Metabolism: A Symbiosis Between Neurons and Mller Cells 180
2.5.1 Energy Metabolism 180
2.5.1.1 Metabolic Glio-Neuronal Symbiosis 181
2.5.1.2 Glucose Metabolism 182
2.5.1.3 Glycogen Metabolism 183
2.5.1.4 Creatine Metabolism 183
2.5.2 Lipid Metabolism 184
2.5.3 Metabolism of Toxic Compounds 184
2.6 Other Glio-Neuronal Interactions in the Retina 185
2.6.1 Recycling of Photopigments 185
2.6.1.1 pH Homeostasis and CO 2 Siphoning 186
2.6.1.2 Transcytosis of Retinoschisin 187
2.6.1.3 Metal Ion Homeostasis 187
2.7 Mutual Signal Exchange Between Retinal Neurons and Mller Cells 188
2.7.1 M--ller Cells Can Sense -- And Respond to -- Retinal Neuronal Activity 188
2.7.1.1 Glutamate Receptors 189
2.7.1.2 Purinergic Receptors 197
2.7.1.3 GABAergic Receptors 206
2.7.1.4 Glycinergic Receptors 207
2.7.1.5 Cholinergic Receptors 209
2.7.1.6 Catecholaminergic Receptors 209
2.7.1.7 Dopaminergic Receptors 210
2.7.1.8 VEGF Receptors 210
2.7.1.9 Thrombin Receptors 212
2.7.1.10 Peptidergic Receptors 212
2.7.1.11 Receptors for Neurotrophic Factors 214
2.7.1.12 Steroid Hormone Receptors 214
2.7.1.13 Receptors for Extracellular Matrix Components 215
2.7.1.14 Other Receptors 216
2.7.2 Müller Cells May Modulate Retinal Neuronal Activity 217
2.7.2.1 Release of Glutamate 217
2.7.2.2 Release of D-Serine 218
2.7.2.3 Release of Purinergic Receptor Agonists 220
2.7.2.4 Release of GABA 223
2.7.2.5 Release of Acyl-CoA-Binding Protein 223
2.7.2.6 Release of Retinoic Acid 223
2.7.2.7 Production of Nitric Oxide 224
2.8 Physiological Mller Cell-Neuron Interactions: A Short Summary 225
3 Müller Cells in the Diseased Retina 227
3.1 Reactive Mller Cells General Properties and Roles 227
3.1.1 Müller Cell Gliosis 227
3.1.1.1 The üJanus Faceü of Müller Cell Gliosis 227
3.1.1.2 Unspecific and Specific Müller Cell Responses 229
3.1.1.3 Heterogeneity of Müller Cell Responses 231
3.1.1.4 ''Conservative'' and Massive Gliosis 232
3.1.1.5 Resistance of Müller Cells to Pathogenic Stimuli 232
3.1.1.6 Primary Müller Cell Injuries 234
3.1.1.7 A Network of Reactive Gliosis 235
3.1.1.8 Glial Scar Formation 236
3.1.1.9 Upregulation of Intermediate Filaments 239
3.1.2 Neuroprotection 241
3.1.3 Müller Cell Proliferation 247
3.1.3.1 Regulation of Müller Cell Proliferation 248
3.1.3.2 Purinergic Stimulation of Müller Cell Proliferation 251
3.1.3.3 Involvement of Calcium-Permeable Channels in Müller Cell Proliferation 252
3.1.3.4 Involvement of BK Channels in Müller Cell Proliferation 253
3.1.3.5 Growth Factor Stimulation of Müller Cell Proliferation 254
3.1.3.6 Other Mitogenic Factors 256
3.1.3.7 Antiproliferative Factors 257
3.1.4 Müller Cells as Progenitor Cells in the Adult Retina ü Müller Stem Cells 258
3.1.5 Immunomodulatory Role of Müller Cells 261
3.2 Involvement and Role(s) of Mller Cells in Specific Retinal Disorders 263
3.2.1 Retinal Ischemia-Reperfusion Injury 263
3.2.1.1 Alterations in the Membrane Conductance of Müller Cells 265
3.2.2 Retinal Detachment 268
3.2.2.1 Müller Cell Response to Retinal Detachment 270
3.2.2.2 Contribution of Müller Cell Dysfunction to Retinal Degeneration 275
3.2.2.3 Glial Inhibition of Retinal Regeneration 276
3.2.3 Proliferative Retinopathies 277
3.2.3.1 Composition of Epiretinal Membranes 278
3.2.3.2 Pathogenic Factors of Epiretinal Membrane Formation 279
3.2.3.3 Soluble Factors Involved in Proliferative Retinopathies 282
3.2.3.4 Müller Cell Physiology in Proliferative Retinopathies 289
3.2.3.5 Peeling of Epiretinal Membranes 291
3.2.4 Diabetic Retinopathy 292
3.2.4.1 Müller Cell Membrane Physiology in Diabetic Retinopathy 295
3.2.5 Macular Edema 297
3.2.5.1 Pathogenic Factors 299
3.2.5.2 Vasogenic Edema 299
3.2.5.3 Cytotoxic Edema and Fluid Absorption 300
3.2.5.4 Stimulation of the Fluid Absorption 302
3.2.6 Neovascularization 304
3.2.7 Retinal Light Damage 306
3.2.8 Hepatic Retinopathy 308
3.2.9 Retinitis Pigmentosa 309
3.2.10 Glaucoma 310
3.2.11 Retinoschisis 311
4 Conclusions and Perspectives 314
References 316
Index 406

Produkt-Details

• Erscheint lt. Verlag: 10.3.2010
• Zusatzinfo: XIV, 417 p.
• Verlagsort: New York
• Sprache: englisch
• Themenwelt: Medizin / Pharmazie ► Medizinische Fachgebiete ► Augenheilkunde
• Themenwelt: Medizin / Pharmazie ► Studium
• Themenwelt: Naturwissenschaften ► Biologie ► Humanbiologie
• Themenwelt: Naturwissenschaften ► Biologie ► Zellbiologie
• Themenwelt: Naturwissenschaften ► Biologie ► Zoologie
• Themenwelt: Technik
• Schlagworte: axon path • edema • gene therapy • glial • neurons • Neurotransmitter • Ophthalmology • Regulation • Retinopathy
• ISBN-10: 1-4419-1672-5 / 1441916725
• ISBN-13: 978-1-4419-1672-3 / 9781441916723