Retina and its Disorders (eBook)

Joseph Besharse, Dean Bok (Herausgeber)

eBook Download: PDF

2011 | 1. Auflage
910 Seiten
Elsevier Science (Verlag)
978-0-12-382199-7 (ISBN)

Infos

This selection of articles from the Encyclopedia of the Eye covering retina, optics/optic nerve and comparative topics constitutes the first reference for scientists, post docs, and graduate students with an interest beyond standard textbook materials. It covers the full spectrum of research on the retina - from the basic biochemistry of how nerve cells are created to information on neurotransmitters, comparisons of the structure and neuroscience of peripheral vision systems in different species, and all the way through to injury repair and other clinical applications. - The first single volume to integrate comparative studies into a comprehensive resource on the neuroscience of the retina - Chapters are carefully selected from the Encyclopedia of the Eye by one of the world's leading vision researchers - The best researchers in the field provide their conclusions in the context of the latest experimental results

Inhalt

Front Cover 1
The Retina and its Disorders 4
Copyright Page 5
Contributors 6
Preface 12
Contents 14
Acuity 18
Glossary 18
Detection and Resolution Acuity 18
Measurement of Visual Acuity 18
Reporting Visual Acuity 20
Optical and Neural Limits on Visual Acuity 20
Visual Acuity across the Retina 21
Visual Acuity over Life 21
Visual Standards 21
Hyperacuity 21
Dynamic Visual Acuity 22
Further Reading 22
Adaptive Optics 24
Glossary 24
The Benefit of Adaptive Optics in Vision Science 24
Correcting the Eye's Monochromatic Aberration 25
Vision Correction with AO 26
Retinal Imaging with AO 26
Compensating for Eye Motion 26
Imaging Cones 28
The Cone Mosaic and Color Vision 28
Imaging Retinal Pigment Epithelium 30
Imaging Retinal Ganglion Cells 31
Imaging Retinal Vasculature 32
Imaging Retinal Disease 32
Further Reading 33
Alternative Visual Cycle in Muumlller Cells 34
Glossary 34
Visual Cycle in Retinal Pigment Epithelium Cells 34
A Role for Muumlller Cells in Visual Pigment Regeneration 34
A Second Source of Chromophore for Cones 35
Functional Differences between Rods and Cones 35
An Alternate Retinoid Isomerase Activity in Cone-Dominant Retinas 36
11-cis-ROL Dehydrogenase Activity in Cones but Not in Rods 36
An Alternate Visual Cycle that Mediates Pigment Regeneration in Cones 37
A New Role for IRBP 37
Alternate Visual Cycle in Rod-Dominant Species 38
Further Reading 38
Anatomically Separate Rod and Cone Signaling Pathways 39
Glossary 39
Rod and Cone Photoreceptors 39
Cone Postreceptoral Circuitry 39
Lateral Communication Networks 41
Gap Junctions 41
Horizontal Cells 41
Amacrine Cells 41
Ganglion Cells 42
Multiple Rod Signaling Pathways 42
Concluding Statements 44
Acknowledgments 44
Further Reading 44
Anatomy and Regulation of the Optic Nerve Blood Flow 45
Glossary 45
Introduction 45
Anatomy of the Vascular Supply 45
Retina 46
Choroid 47
Optic Nerve 47
Histology of Blood Vessels in the Optic Nerve 49
Regulation of Ocular Blood Flow 51
Technology for Measuring Ocular Blood Flow 52
Color Doppler Imaging 52
Angiography 52
Blue Field Entotpic Technique 53
Laser Doppler Velocimetry 53
Retinal Vessel Diameters 53
Laser Speckle Technique 53
Laser Doppler Flowmetry 53
Pulsatile Ocular Blood Flow 53
Optical Doppler Tomography 54
Future Studies 54
Further Reading 54
Animal Models of Glaucoma 55
Glossary 55
Mammalian Models 55
Primate Models of Glaucoma 55
Rodent Models of Glaucoma 56
Rat Models 56
Mouse Models 57
Pressure-induced mouse models 57
Normal-tension mouse models 58
Developmental mouse models 58
Other Mammalian Models 58
Nonmammalian Models 59
Zebrafish 59
Other Nonmammalian Models 59
Conclusion 59
Further Reading 59
Blood-Retinal Barrier 61
Glossary 61
Blood-Retinal Barrier 61
Inner Blood-Retinal Barrier 62
Retinal endothelial cells 62
Retinal endothelial TJs 63
Muumlller cells, astrocytes, and pericytes 63
Outer Blood-Retinal Barrier 64
RPE cells 64
RPE tight junctions 64
Polarity of the outer and inner barriers: TJ modulation 64
Other factors regulating the molecular movement in the eye 64
The Blood-Retinal Barrier and Ocular Immune Privilege 65
Clinical evaluation of the blood-retinal barrier 65
Blood-retinal barrier and macular edema 66
Relevance of BRB to Treatment of Retinal Diseases 66
Further Reading 67
Breakdown of the Blood-Retinal Barrier 68
Glossary 68
Introduction 68
Tight Junctions 68
Vesicular Transport 69
Role of Inflammation 69
Molecular Mechanisms 70
Assessing BRB Breakdown 71
Inhibiting BRB Breakdown 72
Prospects for the Future 73
Conclusions 73
Acknowledgments 73
Further Reading 73
Breakdown of the RPE Blood-Retinal Barrier 75
Glossary 75
Introduction 75
RPE Barrier Structure 75
RPE Barrier Functions 76
Transport and Fluid Flow within the RPE and Eye 76
RPE Na,K-ATPase pump 77
Methods to Assess RPE Barrier Structure and Function 77
Tight Junction Structure 77
Barrier Function 77
Assays That Measure Barrier Properties of RPE 77
Clinical Conditions Associated with Breakdown of the RPE Barrier 78
Inflammation/Infection 79
Age-Related Macular Degeneration 79
Diabetes Mellitus 81
Proliferative Vitreoretinopathy 81
Drug Toxicity 81
Central Serous Retinopathy 82
Retinitis Pigmentosa 83
Growth Factors 83
Studies to Increase the Function of the BRB 84
Further Reading 84
Circadian Metabolism in the Chick Retina 85
Glossary 85
Introduction 85
Clock Gene Expression 85
Circadian Regulation of Cyclic AMP in Retina 86
Circadian Regulation of Melatonin Biosynthesis 88
Other Rhythms of Gene Expression and Metabolism in the Chick Retina 90
Conclusion 91
Acknowledgments 91
Further Reading 91
Central Retinal Vein Occlusion 92
Glossary 92
Pathogenesis 92
Site of Occlusion in CRVO 93
Demographic Characteristics 93
Clinical Features 94
Differentiation of Ischemic from Nonischemic CRVO 95
Course of CRVO 96
Complications 96
Management of CRVO 98
Medical Treatments 99
Surgical or Invasive Treatments 99
Panretinal Photocoagulation 100
Primary Factor Responsible for Blindness in Ischemic CRVO with Neovascular Glaucoma 102
Overall Conclusions About Advocated Treatments for CRVO 102
Natural History of Visual Outcome in CRVO 102
Investigations of CRVO Patients 102
Further Reading 103
Choroidal Neovascularization 104
Glossary 104
Choroidal Neovascularization 104
Clinical Detection of CNV 104
Histopathology of CNV 106
Animal Models of CNV 107
Laser-induced CNV 107
Growth factor models 107
Pathobiology of CNV 108
Angiogenesis 108
Vascular endothelial growth factor 108
Other angiogenic factors 108
Natural inhibitors of angiogenesis 108
Inflammation 108
Monocytes and macrophages 108
Complement 109
Vasculogenesis 109
Therapy of CNV 109
Variants of Pathologic Neovascularization in NVAMD 110
Polypoidal choroidal vasculopathy 110
Retinal angiomatous proliferation 111
Future Directions 112
Further Reading 112
Chromatic Function of the Cones 113
Glossary 113
Introduction 113
Photopigments and Phototransduction 114
Fundamental Spectral Sensitivities 114
Prereceptoral Attenuation 115
Cone Spectral Sensitivities 115
Template for Cone Spectral Sensitivity 116
Cone Gains and von Kries Scaling 116
Isolating Cone Responses 116
Selective Chromatic Adaptation 117
Silent Substitution 117
Rod Intrusion 118
Spatial Densities 118
Individual Variations 118
Retinal Distributions 118
Eccentricity and Chromatic Function 119
Postreceptoral Spectra 119
Cone Opponency 119
Advantages of Cone Opponency 119
Further Reading 120
The Circadian Clock in the Retina Regulates Rod and Cone Pathways 122
Glossary 122
Introduction 122
Rod and Cone Pathways in the Fish Retina 123
Day/Night Differences in the Light Responses of Neurons in the Fish Outer Retina 124
The Circadian Clock in the Retina, and Not the Retinal Response to the Ambient Illumination, Controls Rod-Cone Coupling 125
The Circadian Clock in the Mammalian Retina Controls Rod-Cone Coupling 126
A Circadian Clock Pathway in the Retina 126
Functional Implications of Circadian Clock Control of Rod-Cone Coupling 127
Further Reading 128
Circadian Photoreception 129
Glossary 129
Introduction 129
Nonvisual Photoreception 129
Melanopsin and the Mammalian ipRGC 131
Functions of ipRGCs 132
Further Reading 134
Circadian Regulation of Ion Channels in Photoreceptors 135
Glossary 135
Circadian Oscillators Regulate the Functions of the Visual System 135
Circadian Regulation of Photoreceptors 135
Ion Channels in Photoreceptors 136
Circadian Regulation of cGMP-gated Cation Channels 136
Signaling Pathways Leading to the Circadian Regulation of CNGCs 137
Circadian Phase-Dependent Modulation of Cone CNGCs by Dopamine 137
Modulation of Cone CNGCs by Somatostatin 138
Circadian Regulation of L-VGCCs 138
Circadian Regulation of Other Photoreceptor Ion Channels: Potassium Channels (K+ Channels) 139
Conclusion 139
Further Reading 140
Circadian Rhythms in the Fly's Visual System 141
Glossary 141
The Fly's Visual System 141
The Fly's Circadian System 143
Circadian Rhythms in the Retina of the Compound Eye 144
Circadian Rhythms in the First Visual Neuropil (Lamina) 146
Circadian Plasticity of Synaptic Contacts 146
Circadian Plasticity of Second-Order Neurons and Glial Cells 147
Circadian Rhythms in Organelles inside Photoreceptor Terminals 148
Neurotransmitter Regulation of Circadian Rhythms in the Visual System 148
Larval Visual System 149
Circadian Circuits in the Fly's Visual System 149
The Role of Circadian Clocks in the Visual System 149
Further Reading 150
Relevant Websites 150
Color Blindness: Acquired 151
Glossary 151
Introduction 151
Classifying Acquired Color Blindness 151
Discriminating Acquired from Inherited Color Blindness 152
Conditions Resulting in an Acquired Color-Vision Defect 153
Ocular Diseases 153
Age-related macular degeneration 153
Glaucoma 153
Retinitis pigmentosa 153
Cataract 154
Diabetic retinopathy 154
Optic neuritis 154
Cortical Defects 154
Cerebral achromatopsia 154
Neurodegenerative diseases 154
Toxin-Induced Defects 155
Digitalis 155
PDE5 inhibitors 155
Chloroquine 155
Ethambutol 155
Vitamin A deficiency 156
Exposure to metals and chemicals 156
Conclusion 156
Further Reading 156
Color Blindness: Inherited 157
Glossary 157
Introduction 157
Photoreceptor Basis of Human Color Vision 157
Genetic Basis of Human Color Vision 158
Red-Green Color-Vision Deficiencies 160
Tritan Color-Vision Deficiencies 161
Blue-Cone Monochromacy 163
Achromatopsia 163
Conclusion 163
Further Reading 164
The Colorful Visual World of Butterflies 165
Glossary 165
Introduction 165
The Butterflies and Their Evolutionary History 165
Color Vision and the Butterfly Eye 166
Spectral Heterogeneity of Butterfly Eyes 167
Diversification of Visual Pigments via Gene Duplication and Positive Selection 168
Diversification of Photoreceptor Types via Filtering Pigments 170
Evolution of Sexually Dimorphic Eyes: Opsin Duplications and Sex-Specific Filtering Pigment Expression 171
Ecological Significance of Butterfly Visual System Diversity 171
Conclusions 172
Further Reading 172
Cone Photoreceptor Cells: Soma and Synapse 173
Glossary 173
Introduction 173
Structure 173
Morphology and Topology 173
Axon and Terminal 173
Synapse 175
Invagination and Triad 175
Biophysical Properties 175
Gap Junctions 176
Morphological Implications of Spectral Sensitivity 176
Function 176
Adaptation and Predictive Coding 176
Synaptic Transfer Function 176
Rate of Vesicle Release 177
Electrical Coupling 177
Negative Feedback 178
Theory of Ephaptic Feedback 178
Bandpass Adaptation Filter 179
Conclusion 179
Acknowledgments 179
Further Reading 179
Contrast Sensitivity 180
Glossary 180
Contrast-Detection Threshold 180
Psychophysical Assessment of Vision 180
Spatial Frequency Channels 181
Contrast Sensitivity Function 182
Temporal Contrast Sensitivity 183
Further Reading 185
Coordinating Division and Differentiation in Retinal Development 186
Glossary 186
Introduction 186
A Few Basics of Cell-Cycle Regulation 187
Cyclins and Cdks in Retinal Development 189
The Rb Family in Retinal Development 190
Ink4 CKIs and p19Arf in Retinal Development 191
Cip/Kip CKIs in Retinal Development 191
E2Fs in Retinal Development 192
Separating Rate, Birth, and Exit 192
Distance from Notch Predicts Birth 192
Birth Does Not Require Exit 193
Mechanisms Linking Birth to Exit 194
Conclusion 194
Acknowledgments 195
Further Reading 195
Developmental Anatomy of the Retinal and Choroidal Vasculature 196
Glossary 196
Choroidal Vascular Network 196
Embryology 196
Gross Anatomy 196
Physiology 199
Pathology 199
Hyaloid Vascular Network 199
Embryology 199
Physiology 200
Pathology 200
Retinal Vascular Network 200
Embryology 200
Gross Anatomy 200
Physiology 201
Pathology 202
Further Reading 202
Development of the Retinal Vasculature 203
Glossary 203
Introduction 203
An Overview of Human Adult Retinal Vasculature 203
Vasculature of the Primordial Retina 203
Formation of the Human Retinal Vasculature Takes Place Through Vasculogenesis and Angiogenesis 205
Vasculogenesis: Vascular formation through transformation from VPCs 205
Lack of Involvement of VEGF in Early Stages of Vascularization 210
Angiogenic and anti-angiogenic factors 212
Cell-Cell Interactions in the Formation of the Human Retinal Vasculature 212
Muumlller cell-endothelial cell interactions 212
Pericyte-endothelial cell interactions: Vessel stability 212
Vascular Remodeling 212
Vascularization and the Health of the Eye 213
Conclusions 213
Further Reading 213
Embryology and Early Patterning 215
Glossary 215
Embryology 215
Early Patterning 217
Proximo-Distal Patterning of the Optic Vesicle 217
Specification of the RPE and NR 219
Dorso-Ventral Patterning of the Optic Cup 220
Conclusions 220
Further Reading 221
Relevant Website 221
Evolution of Opsins 222
Glossary 222
Introduction 223
General Opsin Structure and Function 223
Type I and Type II Opsins 223
Major Type II Opsin Classes 223
Cnidops 223
Retinal G-Protein Receptor/Go 225
Rhabdomeric (Gq) 225
Ciliary (Gt) 225
Opsin and Color Vision 225
Molecular Basis of Wavelength Sensitivity 227
Opsin and Modes of Phototransduction Evolution 227
Further Reading 227
Eye Field Transcription Factors 229
Glossary 229
Discovery and Structural Features of Eye- Field Transcription Factors 229
Pax6 229
Six3 229
Six6 229
Rax 230
Lhx2 230
Tbx3 230
Nr2e1 230
The EFTFs are Expressed during and are Required for Normal Eye Formation 231
The EFTFs Form a Self-Sustaining Feedback Network 233
The Coordinated Expression of EFTFs is Sufficient for Eye Formation 233
Conclusions 235
Further Reading 235
Fish Retinomotor Movements 236
Glossary 236
Nature and Occurrence 236
Mechanisms of Force Production for Retinomotor Movements 237
Force Production for Photoreceptor Elongation and Contraction 237
The RPE Cytoskeleton and Force Production for Pigment Granule Dispersion and Aggregation 238
Intracellular Regulation of Retinomotor Movements: The Role of Cyclic Adenosine Monophosphate 239
Regulation of Photoreceptor Retinomotor Movements by Paracrine Messenger 240
Dopamine 240
Adenosine 242
Regulation of Retinomotor Movements in RPE Cells by Paracrine Messengers 242
Functions and Significance of Retinomotor Movements 243
Summary 243
Further Reading 244
GABA Receptors in the Retina 245
Glossary 245
Introduction 245
Vesicular Transporters 245
Plasma Membrane Transporters 246
Neuronal Localization 247
Function 248
Synaptic Receptors 248
Photoreceptors 249
Horizontal Cells 249
Bipolar Cells 249
Amacrine Cells and Ganglion Cells 250
Muumlller's Cells 251
Further Reading 251
Relevant Website 251
Ganglion Cell Development: Early Steps/Fate 252
Glossary 252
Retinal Ganglion Cell Formation 252
Atoh7/Ath5 Function is Critical for RGC Development 252
Integrated Regulation of Atoh7/Ath5 Retinal Expression 253
Atoh7/Ath5 Activates Pou4f/Brn3 Expression in RGCs 254
Pou4f2/Brn3b Controls Numerous RGC Processes 255
Islet1 Acts Parallel to Pou4f2 During RGC Development 255
Conclusion 256
Further Reading 256
Genetic Dissection of Invertebrate Phototransduction 257
Glossary 257
The Drosophila Phototransduction Cascade 259
Genetic Screens for Mutants Defective in Phototransduction Proteins 259
The Photochemical Cycle and the Mechanism Underlying Termination of M Activity 259
Coupling of Photoexcited R to Inositol Phospholipid Hydrolysis 261
Light-Activated Gq Protein 261
Light-Activated PLC 262
The TRP Channels 262
The trp Mutant and the Discovery of the TRP Channel 262
Biophysical Properties of the TRP Channel 262
Lipids Activate the Light-Sensitive Channels in the Dark 265
Organization in a Supramolecular Signaling Complex via the Scaffold Protein Inactivation No Afterpotential D 266
The Photoreceptor Cells Are Sensitive to Single Photons 267
Conclusions 268
Further Reading 268
Relevant Website 268
Hereditary Vitreoretinopathies 269
Glossary 269
Introduction 269
Classification of the Hereditary Vitreoretinopathies 269
Clinical Features of the Hereditary Vitreoretinopathies 269
Vitreoretinopathies Associated with Skeletal Abnormalities 269
Stickler syndrome (OMIM #108300, #604841, and #184840) 269
Kniest dysplasia (OMIM #156550) 270
Spondyloepiphyseal dysplasia congenital (OMIM #183900) 270
Marshall syndrome (OMIM #154780) 270
Knobloch syndrome (OMIM #267750) 273
Marfan syndrome (OMIM #154700) 273
Vitreoretinopathies Associated with Progressive Retinal Dysfunction 274
Wagner syndrome (OMIM #143200) 274
Goldmann-Favre syndrome/enhanced S-cone dystrophy (OMIM #268100) 275
Vitreoretinopathies Associated with Abnormal Retinal Vasculature 275
Familial exudative vitreoretinopathy (OMIM #133780, #601813, and #305390) 276
Autosomal dominant vitreochoroidopathy (OMIM #193220) 276
Vitreoretinopathy Associated with Corneal Changes 276
Snowflake vitreoretinal degeneration (OMIM #193230) 277
Molecular Genetics of the Hereditary Vitreoretinopathies 277
Further Reading 279
Relevant Website 279
Histogenesis: Cell Fate: Signaling Factors 280
Glossary 280
Introduction 280
Notch 280
The Wnt Pathway 281
The Hedgehog Signaling Pathway 282
Transforming Growth Factor-beta 283
Signaling Molecules and Photoreceptor Development 285
Conclusion 286
Further Reading 286
Immunobiology of Age-Related Macular Degeneration 287
Glossary 287
Epidemiology and Clinical Findings of Age-Related Macular Degeneration 287
The Immune System in AMD 288
Histopathology of Drusen 288
Role of Macrophages 288
Adaptive Immune System 289
Infectious Agents 289
Genetics of AMD and Evidence for a Role of Inflammation in the Pathogenesis of AMD 289
Mouse Models of AMD 290
Summary 291
Further Reading 292
Information Processing: Amacrine Cells 293
Glossary 293
Amacrine Cells 293
AC Classification, Form, and Patterns 293
AC Synapses and Neurochemistry 295
ACs and Signal-Processing Fundamentals 296
Examples of AC Networks 297
gamma ACs of the Rod Pathway 297
Gly ACs of the Rod Pathway 298
Small gamma ACs of the Primate Midget BC rarr GC Pathway 298
gamma ACs of the Directionally Selective GC pathway 299
Axonal Cells 299
ACs and Disease 300
Further Reading 300
Information Processing: Bipolar Cells 301
Glossary 301
Further Reading 306
Information Processing: Contrast Sensitivity 307
Glossary 307
Contrast Processing and Adaptation 307
The Spatial Receptive Field 307
The Temporal Receptive Field 308
Receptive Field Properties Explain Contrast Sensitivity Functions 309
Disrupting Specific Retinal Pathways Alters Perceptual Contrast Sensitivity in Selective Ways 309
Physical Limits to Contrast Sensitivity 310
Further Reading 311
Information Processing: Direction Sensitivity 312
Glossary 312
Physiological Functions of DSGCs 312
Synaptic Circuitry of DSGCs 313
Direction-Selective Responses in SAC Processes 315
Integration of Multiple Cooperative Mechanisms for Direction Selectivity 316
Concluding Remarks 316
Acknowledgments 316
Further Reading 317
Information Processing: Ganglion Cells 318
Glossary 318
Ganglion Cell Types 318
Principles of Ganglion Cell Processing 318
Temporal Processing 318
Spatial Processing 319
Center-Surround Receptive Fields 319
Tiling 319
Stimulus Features that Trigger Ganglion Cell Activity 321
Ganglion Cells as Spatiotemporal Filters 321
Ganglion Cells as Specific Feature Detectors 321
Direction-selective (DS) ganglion cells 322
Object motion sensitive (OMS) ganglion cells 323
Saccadic suppression 324
Approach-sensitive ganglion cells 324
Further Reading 325
Information Processing: Horizontal Cells 326
Glossary 326
Introduction 326
Synaptic Interactions and Gap-Junction Coupling of Horizontal Cell Subclasses 327
Ionic Conductances of Horizontal Cells and the Response to Light 328
Cellular Mechanisms of Horizontal Cell Neurotransmission 329
Horizontal Cell Feedback and Feed-Forward 329
Feed-Forward onto Bipolar Cell Dendrites 330
Feedback onto Photoreceptor Terminals 330
Ephaptic Transmission between Horizontal Cells and Photoreceptor Terminals 331
Proton Mediation of Horizontal Cell Feedback 331
Functional Roles of Horizontal Cells 331
Retinal Adaptation 331
Gain Control of Synapses in the Outer Retina 332
Spatial and Temporal Processing 333
Chromatic Processing 333
Conclusions 334
Acknowledgments 334
Further Reading 334
Information Processing in the Retina 335
Glossary 335
Introduction 335
The Outer Retina, Gain and Level Adjustment 335
Bifurcation of the Visual Pathways into ON and OFF streams 336
Horizontal Cell Synaptic Interactions 336
Horizontal Cells and Local Gain Control 336
Interactions at the Inner Retina: Contrast Gain 337
General Organizational Principles 337
Lateral Interactions are Concatenated 337
Mutual Antagonism is a Form of Amplification 337
Redundant Feedforward and Feedback Interactions 337
Interaction between the Two Complementary Visual Streams in the Visual System 337
Inner Retinal Processing: Circuitry for Feature Extraction 338
Amacrine Cell Morphological Types 339
Specific Ganglion Cell Circuitries 339
Directional selectivity 339
Functions of AII Amacrine Cells 340
Further Reading 341
Information Processing: Retinal Adaptation 342
Glossary 342
Light Adaptation 343
Characteristics of Light Adaptation 343
Mechanisms and Sites of Light Adaptation 345
Contrast Adaptation 346
Chromatic Adaptation 347
Dark Adaptation 347
Characteristics of Dark Adaptation 348
Mechanisms of Dark Adaptation 349
Conclusion 349
Further Reading 349
Relevant Websites 349
Optic Nerve: Inherited Optic Neuropathies 350
Glossary 350
Leber's Hereditary Optic Neuropathy 350
Dominant Optic Atrophy (DOA) 352
Recessive Optic Atrophy 352
Other Inherited Conditions with Optic Atrophy 353
Conclusion 353
Further Reading 354
Injury and Repair: Light Damage 355
Glossary 355
Introduction 355
Role of Rhodopsin Activation in Light Damage 356
Mechanisms of Photic Injury: From Gene Expression to the Molecular Pathway 357
Apoptosis Genes 358
Role of Oxidant Stress in Light Damage 358
Role of Inflammation in Light Damage 358
Tissue Remodeling 359
Transcription Factors 359
Identification of Two Nonredundant Mechanisms of Endogenous Protection of Photoreceptors 359
Rhodopsin-Activated Endogenous Protection 360
Identification of Mechanisms for Chronic Light Stress-Induced Endogenous Protection 360
Role of Leukemia Inhibitory Factor 360
Concluding Remarks 361
Further Reading 361
Injury and Repair: Neovascularization 363
Glossary 363
Introduction 363
Mechanisms of Injury 363
Animal Models of NV after Laser- Induced Injury 365
Acute Responses to Retinal Injury 365
Blood-Retina Barrier Breakdown 365
Acute Release of Cytokines 365
Injury-Induced Complement Activation 367
Other Angiogenic Mediators in the Retinal Response to Injury 367
Modulation of the Extracellular Matrix 367
Cellular Response in Injury-Induced NV 367
Neutrophils 368
Macrophages 368
Progenitor/Stem Cells 368
Other Infiltrating Cell Types 368
Resident Tissue Cells 368
Microglia 369
Retinal astrocytes 369
Muumlller cells 369
Cellular Responses to VEGF-A Receptor Binding 369
Conclusion 369
Further Reading 370
Injury and Repair: Prostheses 371
Glossary 371
Rationale for a Prosthetic Device 371
Brain Prosthetic Devices 371
Retinal Prosthetic Devices 372
Clinical Trials 373
Challenges 374
Future Prospects 375
Further Reading 375
Injury and Repair: Retinal Remodeling 377
Glossary 377
Overview 377
Progression 377
Phase 1 378
Phase 2 378
Phase 2+ 379
Phase 3 379
Remodeling Events 379
Reprogramming 379
Rewiring 380
Neuritogenesis 380
Synaptogenesis and Microneuromas 380
Self-Signaling 380
Migration 380
Cell Death 381
MC Remodeling 381
RPE Remodeling 381
Vascular Remodeling 381
Impact of Remodeling on Therapeutics 381
Primary Gene Therapy 381
Survival Factor Therapy 382
Stem/Neuroprogenitor Cell Therapy 382
Retinal Transplantation 382
Secondary Gene Therapies: Photosensitive Proteins 382
Bionic Implants 382
The Importance of Cone Rescue 383
Further Reading 383
Injury and Repair: Stem Cells and Transplantation 384
Glossary 384
Introduction 384
Early Transplant Work 384
Neural Progenitor Cells 384
Retinal Progenitor Cells 385
Induced Pluripotent Stem Cells 385
Stem Cells for Neuroprotection 386
Retinal Transplantation 386
Transplantation Strategies 387
Polymer Substrates 387
Inhibitory Barriers 388
Conclusions 390
Further Reading 390
Relevant Websites 390
Innate Immune System and the Eye 391
Glossary 391
Introduction 391
Passive Innate Defense System 391
Anatomic and Physical Barriers 391
Eyelids and eyelashes 391
Tear film 391
Corneal epithelium 392
Posterior lens capsule 392
Retinal pigment epithelium 392
Chemical Barriers 393
Lysozyme 393
Secretory phospholipase A2 393
Cathelicidin (LL-37) 393
Defensins 393
Lactoferrin 394
Lipocalin-A 394
Secretory IgA 394
Complement 394
Active Innate Defense System 394
Pattern Recognition Receptors 394
Toll-like receptors 394
NOD-like receptors 394
Complement 395
Cytokines, Chemokines, and Effector Cells 396
Initiation and amplification 396
Clearing the pathogen 396
Innate Immune Privilege 396
Link between Innate and Adaptive Immunity 396
Conclusion 397
Further Reading 397
IOP and Damage of ON Axons 398
Glossary 398
Introduction - Intraocular Pressure as a Risk Factor for Glaucoma 398
Biomechanical Engineering Studies 399
Modulation of Glia Behavior at the Optic Nerve Head and Dysfunction of Ganglion Cell Axons 399
Compartmentalized Self-Destruct Pathways and the Pathology of Glaucoma 403
Acknowledgments 404
Further Reading 404
Intraretinal Circuit Formation 406
Introduction 406
Organization of Retinal Circuits of Vertebrates 406
Formation of Retinal Synaptic Laminae 406
Assembly of the Vertical Pathway 406
Retinal Ganglion Cells 408
Bipolar Cells 409
Photoreceptors 410
Synaptogenesis in the Vertical Pathway 410
Assembly of Lateral Circuits 412
Inner Retina - Amacrine Cells 412
Outer Retina - Horizontal Cells 413
Emergence of Function - Spontaneous and Light-Evoked Activity 413
Conclusions 414
Further Reading 415
Ischemic Optic Neuropathy 416
Glossary 416
Classification 416
Nonarteritic Anterior Ischemic Optic Neuropathy 416
Pathogenesis 416
Risk Factors for Development of NA-AION 416
Conclusion 418
Clinical Features of NA-AION 418
Bilateral NA-AION 419
Recurrence of NA-AION in the same eye 420
NA-AION and phosphodiesterase-5 inhibitors 420
Amiodarone and NA-AION 420
Familial NA-AION 420
Management of NA-AION 420
Incipient NA-ION 422
Arteritic AION 422
Pathogenesis 422
Clinical Features of GCA and A-AION 422
Symptoms 422
Signs 422
Laboratory investigations 422
Management of A-AION 423
Differentiation of A-AION from NA-AION 424
Steroid Therapy to Prevent Blindness in GCA 424
Conclusion 424
Posterior Ischemic Optic Neuropathy 425
Classification 425
Pathogenesis 425
Arteritic PION 425
Nonarteritic PION 425
Surgical PION 425
Clinical Features of PION 426
Symptoms 426
Signs 426
Management of PION 427
Arteritic PION 427
Nonarteritic PION 427
Surgical PION 427
Conclusions 427
Further Reading 427
Light-Driven Translocation of Signaling Proteins in Vertebrate Photoreceptors 429
Glossary 429
Introduction 429
Light Dependency of Protein Translocation 429
Hypotheses on the Functional Roles of Protein Translocation 430
What Is the Mode of Protein Translocation: Active Transport or Diffusion? 430
Specific Mechanisms of Protein Translocation 431
Transducin 431
Arrestin 432
Proteins' Return in the Dark 432
Further Reading 432
Limulus Eyes and Their Circadian Regulation 433
Glossary 433
Organization of the Limulus Visual System 433
Lateral Compound Eyes 433
Median Eyes 435
Rudimentary Eyes 435
The Photoreceptors 436
Circadian Organization of the Limulus Visual System 437
Effects of the Clock on Limulus Eyes 437
Structure 437
Physiology 438
Rhabdom Shedding 439
Gene Expression 439
Biochemical Processes Mediating Clock Effects on Limulus Eyes 440
Octopamine and the Activation of a cAMP Cascade 440
Clock-Driven Protein Phosphorylation 440
Conclusion 441
Further Reading 441
Macular Edema 443
Glossary 443
Diagnosis of Macular Edema 444
Anatomy of the Macula 444
Clinical Findings in Macular Edema 445
Clinically Significant Diabetic Macular Edema 445
Findings by Fluorescein Angiography 445
Causes of Macular Edema 449
Treatment of Macular Edema 449
Results from the ETDRS 449
Results of Other Clinical Trials 451
Anti-VEGF Therapies and Macular Edema 451
A Puzzling Question 452
Further Reading 454
Microvillar and Ciliary Photoreceptors in Molluskan Eyes 455
Glossary 455
Microvillar (Rhabdomeric) Photoreceptors 456
Excitation 456
Light Adaptation 458
Ciliary Photoreceptors 459
Excitation 459
Photopigment, G Protein, and Arrestin 460
Guanylate Cyclase 461
Light-Dependent Ion Channels 462
Light Adaptation 462
Further Reading 463
Morphology of Interneurons: Amacrine Cells 464
Glossary 464
AII Amacrine Cells 466
Starburst Amacrines 467
Further Reading 468
Morphology of Interneurons: Bipolar Cells 469
Glossary 469
Introduction 469
Bipolar Cell Types of the Mammalian Retina 469
Midget Bipolar Cells of the Primate Retina 470
Blue Cone Bipolar Cells 470
Clomeleon-labeled ganglion cells, amacrine cells and bipolar cells 471
Diffuse Bipolar Cells 472
Cone Bipolar Cells with Rod Input 472
Immunocytochemical Markers and Transgenic Mouse Lines 472
Synaptic Contacts of Bipolar Cells in the Inner Plexiform Layer 474
Costratification of Pre- and Postsynaptic Partners in the Inner Plexiform Layer 475
Bipolar Cells of Nonmammalian Vertebrates 476
Color-Coded Bipolar Cells in the Turtle Retina 477
Further Reading 477
Morphology of Interneurons: Horizontal Cells 478
Glossary 478
General Morphology and Connectivity 478
Basic Morphology 478
Photoreceptor Contacts 479
Contacts with cones 479
Contacts with rods 480
Population Properties and Gap-Junctional Coupling 481
Diversity of Morphology and Connectivity across Species 481
Variations of Shape 482
Species with Selective Cone Contacts 484
Conclusions and Open Questions 485
Further Reading 485
Relevant Website 486
Morphology of Interneurons: Interplexiform Cells 487
Glossary 487
Introduction 487
Morphology of Dopaminergic Interplexiform Neurons 487
Morphology and Distribution 488
Soma 488
Dendrites 488
Axon-like fine process 489
Synaptic Input to DA Neurons 489
Input from bipolar cells and amacrine cells 490
Input from intrinsically photoreceptive ganglion cells 490
Input from centrifugal fibers 490
Physiology of Dopaminergic Interplexiform Neurons 490
Dopamine Reconfigures Retinal Circuits 490
Light Drives Interplexiform Neurons via Both Conventional and Novel Pathways 491
IPCs Signal Time of Day from the Retinal Clock 492
DA Neurons and Retinal Degenerative Disease 492
Parkinson's Disease 492
Diabetic Retinopathy 492
Human Health Implications of the Retinal Clock 492
Summary 493
Further Reading 493
Neuropeptides: Function 494
Glossary 494
Introduction 494
Peptide Receptor Expression 494
Peptide-Binding Sites and Localization 495
Peptide Receptor messenger RNAs 495
Peptide Receptor Localization 495
Intracellular Signaling 495
Cellular Signaling 496
Ca2+ Imaging and Ion Channel Physiology 496
Functional Studies 499
Electroretinogram Recording 499
Extracellular Recordings 499
Peptide Influence on Transmitter Release 500
Peptide Function 501
Conclusion 502
Acknowledgments 502
Further Reading 502
Neuropeptides: Localization 504
Glossary 504
Introduction 504
Peptide Expression 504
Bioassays and Radioimmunoassays 504
Peptide Localization 505
Peptide Messenger RNA 505
Peptide Immunostaining 506
Peptide Receptor Expression 508
Peptide-Binding Sites and Localization 508
Peptide receptor mRNAs 508
Pharmacological Studies 508
Peptide Receptor Localization 508
Peptide Receptor mRNAs 508
Peptide Receptor Localization 508
Acknowledgments 510
Further Reading 510
Neurotransmitters and Receptors: Dopamine Receptors 511
Glossary 511
Localization of Dopamine Neurons in the Retina 511
Regulation of Dopamine Neuronal Activity 511
Dopamine Neuronal Activity Is Coupled to Dopamine Synthesis and Metabolism 511
Circadian Control of Dopamine Release and Metabolism 512
Dopamine Receptors 512
Functions of Dopamine in the Retina 513
Retinal Pigment Epithelium 513
Photoreceptor Cells 513
Horizontal Cells 513
Bipolar Cells 514
Amacrine Cells 514
Ganglion Cells 514
Muumlller Glial Cells 514
Role of Dopamine in Photopic Visual Processing 515
Dopamine and Circadian Organization of the Retina 515
Dopamine, Retinal Development, Ocular growth, and Myopia 515
Summary 515
Acknowledgments 515
Further Reading 516
Neurotransmitters and Receptors: Melatonin Receptors 517
Glossary 517
Introduction 517
Sites of Retinal Melatonin Synthesis 517
Melatonin Synthesis by Photoreceptors 517
Phylogenetic Relationships between Photoreceptors and Pinealocytes 518
Classification of Melatonin Receptors 518
Sites of Melatonin Receptors in the Retina 518
Melatonin Receptors in Photoreceptor Cells 518
Melatonin Receptors in RPE 519
Melatonin Receptors in Inner Retinal Neurons 519
Effects of Melatonin on Retinal Function 520
Modulation of Neurotransmitter Release 520
Modulation of Photoreceptor Function 520
Further Reading 521
Non-Invasive Testing Methods: Multifocal Electrophysiology 523
Glossary 523
Why Multifocal? 523
The Basic Principle 523
Recording of Multifocal Data 524
Multifocal Stimulators 525
Patient Positioning and Data Collection 525
Data Analysis and Presentation 525
Dealing with Noisy Data 525
How Long Does the Test Take? 525
Some Examples from the Retina Clinic 527
Central Serous Retinopathy 527
Hydroxychloroquine Retinopathy 527
Juvenile X-Linked Retinoschisis 527
Detecting Small Central Dysfunction 528
Applications to Neuro-Ophthalmology and Glaucoma 529
The mfVECP in Optic Neuritis 531
Comparison of the mfVEP and the mfERG in Optic Neuropathies and Glaucoma 531
Comparison of the mfVEP and the ONHC of the mfERG in an Asymmetric Glaucoma Patient 538
Patient with Unknown Vision Loss 540
Summary and Conclusion 540
Acknowledgments 541
Further Reading 541
Optical Coherence Tomography 542
Glossary 542
3D Ultrahigh Resolution Retinal OCT 543
3D Wide-Field Choroidal OCT 544
Cellular Resolution Retinal OCT 544
Functional Retinal Imaging Using OCT 548
Conclusion 551
Acknowledgments 551
Further Reading 551
Optic Nerve: Optic Neuritis 553
Glossary 553
Definition 553
Optic Nerve Anatomy 553
Immunopathogenesis 553
Epidemiology 554
Etiology 554
Symptoms 554
Diagnosis 554
Clinical Examination 554
Visual Evoked Potential 554
Magnetic Resonance Imaging 555
Cerebrospinal Fluid 555
Optical Coherence Tomography 556
Differential Diagnosis 556
Treatment 556
Neuroprotective Treatment Strategies 557
Prognosis 557
Further Reading 557
Pathological Retinal Angiogenesis 558
Glossary 558
Introduction 558
Promoters and Inhibitors of Angiogenesis 558
Promoters of Angiogenesis 559
Vascular endothelial growth factor 559
Placental growth factor 561
Platelet-derived growth factor 561
Notch 562
Tumor necrosis factor-alpha 563
Ephrins and Ephs 563
Angiopoietins 564
Erythropoietin 565
Integrins 565
Matrix metalloproteinases 565
Components of the complement cascade 565
Inhibitors of Angiogenesis 566
Pigment epithelium-derived factor 566
VEGFxxxb isoforms 566
Soluble VEGF receptor 1 566
Complementary regulatory protein CD59 566
Tryptophanyl-tRNA synthase fragment 566
Slit/Roundabout4 566
Other inhibitors 566
New Directions in Antiangiogenic Therapy 566
Conclusions 567
Further Reading 567
Perimetry 568
Glossary 568
Perimetric Techniques 568
Kinetic Perimetry 568
Static Threshold Perimetry 568
Static Suprathreshold Perimetry 569
Test Targets 569
Standard Achromatic Perimetry 570
Short-Wavelength Automated Perimetry 570
High-Pass Resolution Perimetry (Ring Perimetry) 570
Frequency-Doubling Technology Perimeter 571
Reliability Estimates 571
Fixation Accuracy 571
False-Positive Responses 572
False-Negative Responses 572
Analytical Techniques 572
Total Deviation and Pattern Deviation Plots 572
Global Indices 572
Linear Regression 573
Change Probability 573
Further Reading 573
Relevant Websites 574
Photopic, Mesopic and Scotopic Vision and Changes in Visual Performance 575
Glossary 575
Introduction 575
The Concept of Luminous Efficiency Function 577
Quality of Vision and Light Level 578
Spatial Acuity, Spatial Contrast Sensitivity, and Light Level 578
Pupil Size, Higher order Aberrations, and Light Level 579
Flicker Perception 580
Color Vision and Light Level 582
Conclusions 582
Further Reading 583
Photoreceptor Development: Early Steps/Fate 584
Glossary 584
Introduction 584
Photoreceptor Development 585
Rod and Cone Pattern in Human and Mouse Retina 585
Development of Cone and Rod Photoreceptors 585
Factors Affecting Photoreceptor Genesis 586
Early Stages in Photoreceptor Development 586
From RPC to Photoreceptor Precursor 586
From Cone Precursor to Cone Photoreceptor 588
From Rod Precursor to Rod Photoreceptor 589
Maturation of Photoreceptors 590
Current Research in Photoreceptor Development 590
Conclusions 591
Further Reading 591
The Photoreceptor Outer Segment as a Sensory Cilium 592
Glossary 592
Introduction 592
Turnover of the OS and Phototransduction Machinery 592
The Photosensitive Organelle as a Sensory Cilium 593
Evidence for Intraflagellar Transport in Photoreceptors 595
A Special Role for KIF17 in Photoreceptors 596
What Is the IFT Cargo? 597
Summary and Perspective 598
The Photoresponse in Squid 599
Glossary 599
Introduction 599
Molecular Components of Squid Visual Signal Transduction 599
Squid Rhodopsin 599
Squid Visual Guanine Nucleotide-Binding Protein, Gq 602
Squid Visual PLC 603
Light-Activated Ion Channel 603
Desensitization of Visual Signal Transduction 603
Squid Rhodopsin Kinase 603
Squid Visual Arrestin 604
Conclusion 605
Further Reading 605
Phototransduction: Adaptation in Cones 606
Glossary 606
Performance of the Photopic (Cone) System 606
Workhorse of Vision 606
Rapid Response and Moderate Sensitivity 606
Avoidance of Saturation 606
Light Adaptation of the Cones 607
Flashes on Backgrounds: Desensitization and Acceleration 607
Dependence of Sensitivity on Background Intensity: Weber's Law 608
Extremely Rapid Recovery of Cone Photocurrent 609
Molecular Basis of Cone Light Adaptation 610
Reaction Steps Underlying Rapid Recovery of the Cone's Light Response 610
Cone Avoidance of Saturation 611
Modeling of Human Cone Light Adaptation 611
Further Reading 612
Phototransduction: Adaptation in Rods 613
Glossary 613
Vision over a Billion-Fold Range of Light Intensities 613
Performance of the Scotopic (Rod) System 613
The Purpose of Light Adaptation: Optimization of Performance 615
Avoidance of Saturation: Range Extension 615
Extraction of Contrast Information and Optimization of Response Kinetics 615
Light Adaptation of the Rod Photoreceptors: Range Extension, Desensitization, and Acceleration 615
Prevention of Rod Photoreceptor Saturation: Range Extension 615
Desensitization and Acceleration 616
Unaltered Rising Phase, but Accelerated Recovery 616
Saturation of the Rod Photocurrent at Higher Background Intensities 617
Calcium-Dependent Mechanisms of Rapid Light Adaptation in Rod Photoreceptors 617
Role of Calcium: Resensitization through Prevention of Saturation 617
Powerful Negative-Feedback Loop Mediated by Calcium 617
Three Calcium-Sensitive Molecular Pathways 618
Guanylyl cyclase activation 618
Shortened Rast lifetime 618
Channel reactivation 619
Rod Photoreceptor Light Adaptation Independent of Calcium 619
Accelerated Turnover of cGMP 619
Slow Changes in Rods: Light Adaptation or Dark Adaptation? 619
Light-Induced Change in the Dominant Time Constant 619
Light-Induced Translocation of Proteins 620
Dark Adaptation of the Rods: Very Slow Recovery from Bleaching 620
Further Reading 621
Phototransduction: Inactivation in Cones 622
Glossary 622
Cone Signaling Cascade 622
Shutoff of the Light-Activated Cone Opsins 623
Inactivation of Transducin and PDE 624
Restoration of cGMP and Intracellular Calcium Level 624
Conclusions 624
Further Reading 626
Phototransduction: Inactivation in Rods 627
Glossary 627
What Needs to Be Inactivated: Overview of the Signaling Cascade 627
Shutoff of the Light-Activated Rhodopsin 628
Inactivation of Td and PDE 629
Resynthesis of cGMP and Restoration of Calcium Level 629
Light-Dependent Protein Translocation and Rod Signaling 631
Why Rods Do Not Have an Action Potential 632
Conclusions 632
Further Reading 632
Phototransduction in Limulus Photoreceptors 633
Glossary 633
Arrangement of Eyes in Limulus 633
The Microvillus is the Cellular Structure Mediating Visual Transduction 633
Studies of Visual Transduction Using Limulus Ventral Photoreceptors 634
The Light-Sensitive Conductance Consists of the Summed Effect of Conventional Ion Channels 635
The Response of the Ventral Photoreceptor is Mediated by the Phosphoinositide Cascade 636
The PI Cascade Generates at Least Two Intracellular Messenger Molecules 636
Roles of IP3 and Intracellular Ca2+ Ions in Excitation of Limulus Ventral Photoreceptors 637
IP3 Can Release Ca2+ from the SER 637
Released Ca2+ Ions can Activate an Inward Current 638
Light-Induced Ca2+ Release can be Detected before the Electrical Response 638
How Does IP3-Induced Ca2+ Release Activate Inward Current and is this Current Flowing through the Light- Sensitive Conductance? 639
Adaptation, a Decrease in the Sensitivity of the Visual Cascade, is Mediated by Small, Lingering Elevations of Ca2+ 639
Drosophila and Limulus Photoreceptors Operate Differently and Illustrate Two General Mechanisms Coupling the PI Cascade to an E 640
Extension of Phototransduction Mechanisms to other Microvillar Photoreceptor Types 640
Further Reading 640
Phototransduction: Phototransduction in Cones 641
Glossary 641
Introduction 641
Functional Properties of Cones 641
Obstacles for Studying Cone Phototransduction 642
Cone Visual Pigment and Phototransduction 643
Activation of Cone Phototransduction 644
Inactivation of Cone Phototransduction 644
Dark Adaptation of Cones 645
Light Adaptation in Cones 646
Epilog 647
Further Reading 647
Phototransduction: Phototransduction in Rods 648
Glossary 648
Introduction 648
Vertebrate Rods Are Highly Efficient Photon Detectors 648
Phototransduction in Rods: A G-Protein-Signaling Pathway 648
High Quantum Efficiency of Photoactivation 649
The Great Thermal Stability of Rhodopsin 649
The Activation of Transducin Constitutes the First Amplification Step 650
The High Catalytic Power of PDE Accounts For the Second Amplification Step 651
cGMP Is the Second Messenger Mediating Rod Phototransduction 652
The cGMP-Gated Channel Provides the Final Step of Signal Amplification 652
Further Reading 653
Phototransduction: Rhodopsin 654
Glossary 654
Rod Cells and Rhodopsin 654
Structure of Rhodopsin 655
Chromophore-Binding Site 658
Rhodopsin Cycle - Retinal Isomerization 658
Visual Cycle - Rhodopsin Regeneration 659
Vertebrate versus Invertebrate Rhodopsins 660
Signaling Cycle 661
Rhodopsin Interaction with Other Proteins 661
Rhodopsin-G t 662
Rhodopsin-GRK 1 662
Rhodopsin-Arrestin 662
Mutations in Rhodopsin and Retinal Diseases 662
Further Reading 663
Phototransduction: The Visual Cycle 665
Glossary 665
Clearance of All-trans-RAL from OS Disks 665
Reduction of All-trans-RAL to All- trans- ROL 666
Transfer of All-trans-ROL from Photoreceptors to the RPE 666
Synthesis of Retinyl Esters 667
Retinoid Isomerization 667
Synthesis of 11-cis-RAL Chromophore 668
Regeneration of Rhodopsin or Cone Opsin 668
Regulation of the Visual Cycle 668
Further Reading 668
Physiological Anatomy of the Retinal Vasculature 670
Glossary 670
Arterial Supply of the Retina 670
Central Retinal Artery 670
Cilioretinal Artery 670
Intraretinal Branches of the CRA 671
Retinal Capillary Bed 672
Retinal Venous Drainage 674
Nerve Supply 675
Blood-Retinal Barrier 676
Autoregulation of Retinal Blood Flow 676
Further Reading 677
The Physiology of Photoreceptor Synapses and Other Ribbon Synapses 678
Glossary 678
Anatomy of the Ribbon Synapse 678
Vesicle Pools and Vesicular Release at Synaptic Ribbons 679
Role of the Ribbon in Release 680
Synaptic Proteins 680
Photoreceptor Calcium Channels 681
Role of Intracellular Ca2+ in Release 682
Physiology of Release at Photoreceptor Synapses 682
Disease-Related Mutations in Synaptic Proteins at the Photoreceptor Synapse 683
Further Reading 684
Polarized-Light Vision in Land and Aquatic Animals 685
Glossary 685
Polarized Light in Nature 686
Polarization Sensitivity and Polarization Vision 687
Polarization Responses of Photoreceptor Cells 687
Polarization sensitivity 688
Polarization vision 689
Disentangling polarization and color sensitivity 689
The Contributions of Polarized-Light Perception to Behavior 690
Sensitivity to Circularly Polarized Light 691
Summary 691
Further Reading 692
Post-Golgi Trafficking and Ciliary Targeting of Rhodopsin 693
Glossary 693
Introduction 693
Photoreceptor Polarity 693
Photoreceptor Biosynthetic Membrane Trafficking: Endoplasmic Reticulum, Golgi, and Post-Golgi Transport Carriers 694
Small GTPases of the Rab and Arf Families and Their Regulators in Rhodopsin Trafficking 695
Rabs 695
Arfs 696
SNAREs and their Regulators in Rhodopsin Trafficking 696
ROS is a Modified Primary Cilium 697
Conclusions anSummary 699
Further Reading 700
Relevant Websites 700
Primary Photoreceptor Degenerations: Retinitis Pigmentosa 701
Glossary 701
Background 702
Prevalence 703
Inheritance 703
Autosomal Recessive 703
X-Linked RP 703
Autosomal Dominant 703
Nonsyndromic versus Syndromic Retinal Degeneration 703
Classification of RP 704
Classification by Age of Onset 704
Classification by Fundus Appearance 706
Classification by Functional Loss 707
Mechanism of Disease 707
Clinical Presentation 707
Symptoms 707
Refraction 707
Anterior Segment and Cataract 707
Fundus Findings 707
Diagnostic Tests for RP 708
Dark Adaptation 708
Visual Fields 708
Electroretinograms 708
Fundus Photography/Fluorescein Angiography 709
Optical Coherence Tomography 709
Differential Diagnosis 709
Prognosis in RP 711
Current Treatments 711
Treatable Forms of RP 711
Resources/Support for Patients with RP 711
Optimizing Remaining Vision 712
Vitamin A 713
Docosahexanoic Acid 713
Neuroprotection/CNTF 713
Gene Therapy 713
Autologous RPE Transplantation 714
Stem-Cell-Based Therapies 714
Microelectrode Implants 714
Expression of Photosensitive Proteins 714
Conclusions 714
Further Reading 714
Relevant Websites 714
Primary Photoreceptor Degenerations: Terminology 715
Glossary 715
Histological and Fundus Features of Retinitis Pigmentosa 716
Bone Spicule Pigmentation 716
Waxy Pallor of the Optic Nerve 716
Peripapillary/Optic Nerve Head Drusen 716
Bull's Eye Maculopathy 716
Coats-Like Response 717
Classification of RP by Fundus Pattern 717
Classic Pattern for RP 717
Inverse RP 717
Concentric RP 718
Sector RP 718
RP Sine Pigmento 718
Tapetal-Like Reflex/Sheen 718
RP with Preserved Peri-Arteriolar RPE 718
Pigmented Paravenous Retinochoroidal Atrophy 719
Fundus Albipunctata 719
Retinitis Punctata Albescens 719
Gyrate Atrophy 719
Choroideremia 720
Syndromic Forms of RP 720
Abetalipoproteinemia 720
Alstroumlm Syndrome 721
Bardet-Biedl Syndrome 721
Chronic Progressive External Ophthalmoplegia/Kearns-Sayre Syndrome 721
Friedreich's Ataxia 721
Vitamin E Deficiency 721
Incontinentia Pigmenti (Bloch-Schulzberg Syndrome) 721
Joubert Syndrome 721
Mucopolysaccharide Disorders 721
Neuronal Ceroid Lipofuscinosis (Batten Disease) 721
Infantile Refsum Disease 722
Adult Refsum Disease 722
Senior-Loken Syndrome 722
Spinocerebellar Ataxia Type 7 722
Usher Syndrome 722
Visual Testing in RP 722
Terminology of Light Adaptation 722
Dark Adaptation 722
Visual Fields 722
ERG Terminology 722
Full-Field ERG 722
Multifocal ERG 723
Rod-Isolated ERG Response 723
Mixed Rod-Cone ERG Response 723
Cone-Isolated ERG Response 723
Further Reading 723
Relevant Websites 724
Proliferative Vitreoretinopathy 725
Glossary 725
Introduction 725
Definition 725
Location of PVR Membranes 725
The Significance of Membrane Formation in PVR 725
The Cells Involved in PVR 726
Glial Cells 727
RPE Cells 728
Fibroblastic Cells 728
Macrophages 728
Vascular Elements 728
Other Cells 728
The Extracellular Matrix in PVR Membranes 728
Pathogenesis and Natural History 729
Intraretinal PVR 730
Incidence and Risk Factors 730
Clinical Classification of Proliferative Vitreoretinopathy 731
Management 731
Outcomes 732
Conclusions 732
Further Reading 732
Relevant Website 733
Retinal Cannabinoids 734
Glossary 734
Marijuana and the Endocannabinoids 734
Synthesis and Release 734
Inactivation 734
Receptors 734
Distribution and Function 735
Cannabinoids and Ocular Tissues 736
Cannabinoids - Retinal Anatomy 736
Biochemical Assay 736
Localization - Cannabinoid Receptors 736
Localization - Metabolizing Enzymes 737
Cannabinoids - Retinal Physiology 737
Effects on Transmitter Release 737
Effects on Ganglion cells 738
Effects on Bipolar Cells 738
Cannabinoids and Photoreceptors 738
Voltage-Gated Currents 738
WIN 55,212-2 Affects the Cone Light Response 741
Cannabinoids - Development and Neuroprotection 741
Conclusion 741
Further Reading 742
Relevant Websites 742
Retinal Degeneration through the Eye of the Fly 743
Glossary 743
The Compound Eye and Phototransduction 746
Genetic Screens Identify Retinal Degeneration Loci 747
Retinal Degenerations in Flies and Humans 747
Mechanisms of Retinal Degenerations 748
Light-Dependent Retinal Degenerations 748
Light-Independent Retinal Degenerations 748
Retinal Degenerations Caused by Mutations in Dual-Role Proteins 749
Summary 749
Acknowledgments 749
Further Reading 750
Relevant Website 750
Retinal Ganglion Cell Apoptosis and Neuroprotection 751
Glossary 751
Introduction 751
Apoptosis 751
Apoptosis in Glaucoma 751
Diagnosis and Measuring Glaucoma Progression 751
Current Treatments for Glaucoma 752
Neuroprotection 753
Research Models 753
In Vitro Glaucoma Models 753
In Vivo Glaucoma Models 753
Mechanisms of Apoptosis and Development of Neuroprotective Agents 753
Neurotrophic Factor Withdrawal 753
NFs as Neuroprotective Agents 753
Excitotoxicity 754
NMDA-Antagonists and Neuroprotective Agents 755
Reactive Oxygen Species 756
Mitochondrial Dysfunction and ROS Generation 756
Antioxidants as Neuroprotective Agents 757
Protein Misfolding 757
Reduction of Misfolded Proteins in Neuroprotection 758
Glial-Neuronal Interactions 758
Extracellular Matrix Degradation 759
Neuroprotective Vaccine 760
Summary 760
Further Reading 760
Retinal Histogenesis 762
Glossary 762
Birthdating 762
Lineage Tracing 763
Environmental Challenge 765
Transcription Factors and Competence 767
Conclusions 768
Further Reading 769
Retinal Pigment Epithelial-Choroid Interactions 770
Glossary 770
Introduction 770
RPE-C horoid Complex Development 770
RPE Development 770
Choroid Development 771
BrM Development 772
RPE-C horoid Complex: Structure and Function 772
RPE Structure and Function 772
Choroid Structure and Function 772
BrM Structure and Function 773
RPE-C horoid Interactions 773
Interactions During Development 773
Interactions in the Adult 774
Growth factor secretion 774
Receptor expression 774
Isoform-specific VEGF mouse model 774
Choroidal change impact on RPE 774
RPE-C horoid Changes with Age 775
BrM Changes 775
Gene Expression 775
Conclusions 776
Further Reading 777
Retinal Pigment Epithelium: Cytokine Modulation of Epithelial Physiology 778
Glossary 778
Introduction 778
Human RPE: Morphology, Polarity, and Function 779
pHi - Induced Changes in Fluid Absorption 779
Modulation of SRS Metabolic Load and Chemical Composition 780
Oxidative Stress 783
RPE-I mmune System Interactions in and around the SRS 784
Modulation of RPE Proliferation and Migration by Cytokines and Growth Factors 784
IFNgamma Regulation of RPE Fluid Transport 787
Leukocyte Migration across the RPE: A Model of Disease Progression 788
Further Reading 789
RPE Barrier 790
Glossary 790
Introduction 790
Structure and Function 791
Tissue Level 791
Cellular Level 792
Molecular Level 792
Regulation of RPE Tight Junctions 794
Clues from Embryonic Maturation 794
Assembly of Tight Junctions during Differentiation 794
Culture Models to Study Regulation of the Outer Blood-Retinal Barrier 795
RPE in the Larger Context of Ocular Biology and Disease 796
Further Reading 796
Retinal Vasculopathies: Diabetic Retinopathy 798
Glossary 798
Background 798
Risk Factors for DR 799
Pathogenesis 799
Classifications 801
Nonproliferative Diabetic Retinopathy 801
Macular Edema 802
Proliferative Diabetic Retinopathy 803
Screening for Diabetic Retinopathy 805
Further Reading 805
Retinopathy of Prematurity 807
Glossary 807
Clinical Background 807
Epidemiology 807
Clinical Classification of ROP 807
Management of ROP 808
Treatment of ROP 809
Acute neovascular stages 809
Fibrovascular stages/retinal detachment 809
Visual rehabilitation in preterm infants 812
Genetics Related to ROP 812
Pathophysiology of ROP 812
Role of Oxygen in Retinal Development 812
Animal Models of Severe ROP 813
Mouse OIR (model of aggressive posterior ROP) 813
Rat 50/10 OIR (model of peripheral severe ROP) 813
Role of Avascular Retina 813
Role of Growth Factors 815
Vascular Endothelial Growth Factor 815
IGF-1 - IGF 1BP3 815
Erythropoietin 815
HIF 1alpha 815
Role of Oxidative Stress 815
Future Treatment Considerations 816
Further Reading 816
Rhegmatogenous Retinal Detachment 818
Glossary 818
Pathophysiology 818
Clinical Features 818
Symptoms 818
Signs 819
Break type - identification 819
Retinal tears 819
Retinal round holes 819
Retinal dialyses 820
Break localization - principles based on topography of RRD 820
Superotemporal and superonasal 820
Midline (12 o'clock meridian) and total detachments 820
Inferior 820
Chronic RRD 820
Differential Diagnoses 820
Management 821
Conservative 821
RRD due to retinal tear 821
RRD due to retinal hole or dialysis 821
Laser Demarcation 821
RRD due to retinal tear 822
RRD due to retinal hole or dialysis 822
Pneumatic Retinopexy 822
RRD due to retinal tear 823
RRD due to retinal hole or dialysis 823
Scleral Buckling 823
RRD due to retinal tear 823
RRD due to retinal hole or dialysis 823
Vitrectomy 823
RRD due to retinal tear 823
RRD due to retinal hole or dialysis 824
Outcomes 824
Pneumatic Retinopexy 824
Scleral Buckling 825
Pars Plana Vitrectomy 825
Complications 825
Pneumatic Retinopexy 826
Scleral Buckling 826
Pars Plana Vitrectomy 826
Treatment Failure 826
New Developments 826
Further Reading 826
Rod and Cone Photoreceptor Cells: Inner and Outer Segments 828
Glossary 828
Further Reading 831
Rod and Cone Photoreceptor Cells: Outer Segment Membrane Renewal 832
Glossary 832
Further Reading 835
Rod Photoreceptor Cells: Soma and Synapse 836
Glossary 836
Introduction 836
Structure 836
Morphology and Topology 836
Axon and Terminal 836
Synapse 837
Invagination 838
Biophysical Properties 838
Gap Junctions 838
Function 838
The Single-Photon Signal and Noise 838
Sources of Noise 838
Synaptic Transfer Function: High Gain and Temporal Filtering 839
Rate of Vesicle Release 839
Synaptic Transfer Function: Nonlinear Threshold 839
Electrical Coupling in Starlight 840
Electrical Coupling in Twilight 840
Negative Feedback 840
Conclusion 841
Acknowledgments 841
Further Reading 841
The Role of the Vitreous in Macular Hole Formation 842
Glossary 842
Vitreous Anatomy and Biochemistry 842
Vitreous Traction 842
Vitreoretinal Interface 843
Confounding Observations 844
Summary 845
Further Reading 845
Secondary Photoreceptor Degenerations: Age-Related Macular Degeneration 847
Glossary 847
Introduction 847
Incidence 847
The Macula 847
Clinical Symptoms 848
Histopathology 849
Risk Factors 849
Genetics 850
CFH 850
ARMS2/HTRA1 851
Treatments 851
Further Reading 851
Relevant Websites 852
Secondary Photoreceptor Degenerations 853
Glossary 853
Introduction 853
Mechanisms of Secondary Photoreceptor Death 856
Further Reading 857
Relevant Website 857
Unique Specializations - Functional: Dynamic Range of Vision Systems 858
Glossary 858
Introduction 858
Rods versus Cones 858
The Pathways Concept 858
Rod Bipolar Pathway 859
Signal transfer from rods to rod bipolar cells 859
Signal transfer from rod bipolar cells to AII amacrine cells 860
Ganglion cell sensitivity 860
Rod-Cone Pathway 861
Rod-OFF Pathway 861
Cone Pathways 862
Adaptation to Mean Background Light 862
Adaptation: Rod Pathways 862
Adaptation: Cone Pathways 862
Conclusions 863
Further Reading 863
Xenopus laevis as a Model for Understanding Retinal Diseases 864
Glossary 864
Introduction 864
Early Work on X. laevis - Biochemistry, Electrophysiology, and Microscopy 864
X. laevis as a Model for Vitamin A Deprivation 865
X. laevis as a Model for Glaucoma 865
X. laevis and Studies of the Transport of Rhodopsin 866
Modeling RP in Transgenic X. laevis 866
Inducible RD 868
Other Transgenic X. laevis Models of Retinal Disease 868
X. laevis as a Model for Eye Development/Developmental Disorders 868
X. laevis Models of Retinal Regeneration 868
Summary 869
Further Reading 869
Zebra Fish as a Model for Understanding Retinal Diseases 870
Glossary 870
Introduction 870
Retinal Disease 871
Animal Models of Vision 871
The Advantages and Techniques of the Zebrafish Model System 871
Evaluating zebrafish vision 873
The Visual System: Phosphodiesterase and Phototransduction 873
Retinal Degeneration in pde6 Mutants: Primary Degeneration 874
Retinal Degeneration in pde6 Mutants: Secondary Retinal Degeneration, the Bystander Effect - Models and Mechanisms 874
Levels of the Bystander Effect in Photoreceptor Degeneration 875
Zebrafish Models of Retinal Degeneration: Mutations in pde6c 875
pde6cw59 875
els 877
Pde6 Structure 877
Conclusion 879
Further Reading 879
Zebra Fish-Retinal Development and Regeneration 880
Glossary 880
Introduction 880
Embryonic Eye Patterning 881
Zebrafish Eyes Form from a Single Field in the Anterior Neural Plate 881
The Laminar Structure of the Retina Forms as Cells Exit the Cell Cycle and Differentiate 881
Addition of Retinal Cells Throughout the Life of a Zebrafish 882
Regeneration in the Zebrafish Retina 882
Zebrafish regenerate all retinal neurons 882
Constant Intense Light Kills Photoreceptors, Which Are then Regenerated by M& uuml
Discovery and Analysis of Candidate Genes Involved in Retinal Regeneration 886
Events Underlying Regeneration of the Light- Damaged Retina 888
Vestigial Retinal Regeneration Activity in Mammals 889
Similarities and Differences of Development with Retinal Ontogeny/Genesis 889
Further Reading 889
Subject Index 892

Produkt-Details

• Erscheint lt. Verlag: 19.4.2011
• Sprache: englisch
• Themenwelt: Medizin / Pharmazie ► Medizinische Fachgebiete ► Augenheilkunde
• Themenwelt: Medizin / Pharmazie ► Medizinische Fachgebiete ► Neurologie
• Themenwelt: Naturwissenschaften ► Biologie ► Humanbiologie
• Themenwelt: Naturwissenschaften ► Biologie ► Zoologie
• ISBN-10: 0-12-382199-1 / 0123821991
• ISBN-13: 978-0-12-382199-7 / 9780123821997