Visual Transduction And Non-Visual Light Perception (eBook)

Joyce Tombran-Tink, Colin J. Barnstable (Herausgeber)

eBook Download: PDF

2008 | 2008
XI, 509 Seiten
Humana Press (Verlag)
978-1-59745-374-5 (ISBN)

Infos

This book reveals not only how the eye evolved into an organ of vision, but also describes how molecular mechanisms of key molecules operate in the phototransduction cascade. In this groundbreaking text, experts also explain mechanisms for sensing radiation outside of the visible wavelengths. Comprehensive and penetrating, the book brings together the mechanisms of the visual transduction cascade and is an invaluable text for everyone conducting research in the visual system.

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Remarkable advances have contributed to revolutionizing the study of vertebrate vision. The first step to identifying objects and establishing spatial relationships is the visual transduction cascade, a process that underpins a wide range of ocular diseases and therapies. Toward that, The Visual Transduction Cascade: Basic and Clinical Principles reveals not only how the eye evolved into an organ of vision, but also describes how molecular mechanisms of key molecules (such as transducins, phosphodiesterases, and CyclicGMP metabolizing enzymes) operate in the phototransduction cascade. In this groundbreaking text, experts also explain mechanisms for sensing radiation outside of the visible wavelengths -- a good example of the limitations of the human sensory systems. Comprehensive and penetrating, The Visual Transduction Cascade: Basic and Clinical Principles brings together the developmental, structural, and molecular mechanisms of the visual transduction cascade and is an invaluable text for everyone conducting research in the visual system.

Inhalt

Preface 6
Table of Contents 8
Contributors 10
Companion CD 12
Part I: Evolution of the Visual System 14
An Organ of Exquisite Perfection 15
Optical Path 15
Retinal Photoreception 17
Photoreception Optics 18
Photoreception Biochemistry 19
Membrane Voltages 20
Blind Spot 21
Retinal Pathways 22
Through Pathway 22
Receptive Fields 23
Lateral Pathway 23
Retinal Ganglion Cells 24
Retinal Glia 25
References 25
Part II: Photoreceptor Structure, Function, and Development 27
Development of the Foveal Specialization 29
Introduction 29
Foveal Development 32
Specification of Foveal Location 32
Formation of a Rod-Free Zone 34
Cones, Ganglion Cells, and Initial Pit Formation 36
Deep Foveal Pit Formation 38
Foveal Hypoplasia 39
Conclusions and Perspectives 39
Acknowledgments 41
References 41
An Update on the Regulation of Rod Photoreceptor Development 47
Introduction 47
Brief Overview of Retinal Development and Early Stages of Rod Photoreceptor Differentiation 48
Transcription Factors 49
Basic Helix-Loop-Helix Genes 49
QRX/Rax-L/Rx-L 53
NRL 53
Nuclear Receptors 55
Nr2E3 55
Retinoic Acid/Retinoic Acid Receptors 57
Extracellular Factors and Signal transduction Pathways 58
Wnt/Frizzled Pathway 58
Taurine 59
Ciliary Neurotrophic Factor/Leukemia Inhibitory Factor/Pleiotrophin/Signal Transducer and Activators of Transcription 3/SOCS 59
Conclusions and Future Prospects 61
References 62
Part III: The Retinal Pigment Epithelium and the Visual Cycle 77
Photoreceptor-RPE Interactions 79
Introduction 79
Retinal Adhesion 82
Physiology of Retinal Adhesion 82
Molecular Mechanisms of Retinal Adhesion 82
Significance of Retinal Adhesion for Retinal Function 85
Photoreceptor Outer Segment Renewal 86
Physiology of Outer Segment Disk Assembly and Disk Shedding 86
Physiology of RPE Engulfment of Shed Outer Segment Fragments 87
Molecular Mechanisms of Shedding and RPE Phagocytosis 88
Significance of Photoreceptor Outer Segment Renewal for Retinal Function 93
Perspective 93
Acknowledgments 93
References 94
Molecular Biology of IRBP and Its Role in the Visual Cycle 99
Introduction 99
IRBP Protein Studies 100
IRBP Null Mice 100
IRBP Induces Experimental Autoimmune Uveitis 101
IRBP Expression During Development 101
Variability in IRBP Expression 103
Molecular Biology of IRBP 103
IRBP Genomic Cloning 104
Evolution of IRBP 104
Importance of the STUDY of the Control of Gene Expression 108
Identification of DNA cis-Acting Controlling Elements: In Vitro and In Vivo Experiments 110
Transcription Factors and their Role in the Control of IRBP Expression 112
Rx/rax Transcription Factor 112
NrL Transcription Factor 114
Crx Transcription Factor 115
OTX2 Transcription Factor 116
Transgenic Mice 118
Repressors of IRBP Gene Expression 118
KLF15 118
MOK2 119
Chx10 119
Summary and Conjecture 126
Acknowledgments 127
References 127
Part IV: Visual Signaling in the Outer Retina 135
Regulation of Photoresponses by Phosphorylation 137
Introduction 137
Inactivation of Photoactivated Rhodopsin vy Rhodopsin Kinase 139
Cone-Specific Kinase, GRK7 142
Protein Kinase C 142
Cyclic Adenosine Monophosphate-Dependentprotein Kinase, PKA 144
Cyclin-Dependent Kinase 144
Tyrosine Kinases 144
Mitogen-Activated Protein Kinase Andcalmodulin-Dependent Protein Kinase II 145
Protein Phosphatases 145
Conclusion 145
References 146
The cGMP Signaling Pathway in Retinal Photoreceptors and the Central Role of Photoreceptor Phosphodiesterase (PDE6) 153
Overview of Cyclic Guanosine Monophosphatesignaling Pathways 153
Regulation of Intracellular cGMP Levels in Photoreceptor Cells 154
Downstream Targets of cGMP Action in Photoreceptor Cells 154
cGMP-Dependent Protein Kinase 154
Cyclic Nucleotide-Gated Ion Channels 155
PDE6 Is a High-Affinity cGMP-Binding Protein 155
The Cellular Context of cGMP Signaling In Verteb Rateretinal Photoreceptors 155
Compartmentation of cGMP Signaling in Photoreceptor Outer Segments 155
Physiology of the Photoreceptor Response to Light 156
Biochemical Cascade of Visual Excitation 156
Central Components of the cGMP Signaling Pathway 157
Termination and Adaptation of the Light Response 158
Deactivation of Rhodopsin 159
Deactivation of Transducin 159
Deactivation of PDE6 159
Activation of GC 160
Regulation of the CNG Ion Channel 160
Photoreceptor PDE (PDE6) Structure and Function 160
The Cyclic Nucleotide Phosphodiesterase Superfamily 160
Subunit Composition of Rod and Cone PDE6 Holoenzyme 161
Catalytic Subunit 161
Regulatory GAF Domain 161
Catalytic Domain 163
C-Terminal Prenylation 163
Inhibitory gamma-Subunit 164
PDE6 Has Evolved to Meet the Special Demands of the Central Effector of Visual Transduction 165
PDE6 Regulation 166
Transducin Activation of Rod PDE6 During Visual Excitation 166
Functions of the Regulatory cGMP-Binding GAF Domains of PDE6 166
Potential PDE6 Regulatory Binding Proteins 169
Glutamic Acid-Rich Protein 2 169
17-kDa Prenyl-Binding Protein (PDEdelta) 170
Conclusions 170
Acknowledgments 171
References 171
Rhodopsin Structure, Function, and Involvement in Retinitis Pigmentosa 183
Introduction 183
Historical Perspective 186
Rhodopsin as the Prototypical G Protein-Coupled Receptor 186
Rhodopsin, Localization, and Signaling 187
Dark State and Activation 189
Structural Analysis 191
Electron Cryomicroscopy and Crystal Structure 191
Nuclear Magnetic Resonance 192
Cysteine Mutagenesis and Electron Paramagnetic Resonance 192
Other Approaches 192
Retinitis Pigmentosa 194
Transmembrane RP Rhodopsin Mutants 195
Cytoplasmic RP Rhodopsin Mutants 198
Intradiskal RP Rhodopsin Mutants 198
Implications of Receptor Misfolding 199
Nongenetic Contributions to RP 200
Conclusion 201
References 201
Multiple Signaling Pathways Govern Calcium Homeostasis in Photoreceptor Inner Segments 209
Introduction 209
Overview of Ca2+ Regulation in the Inner Segment 212
Voltage-Operated Calcium Channels Play a Central Role in Inner Segment Calcium Regulation 214
Ca2+ Channels in Rods and Cones 217
Neurotransmission from Rods and Cones to Second-Order Retinal Neurons 218
Photoreceptor Malfunction and Degeneration 220
Therapeutic Strategies 223
Development 224
Acknowledgments 224
References 225
The Transduction Channels of Rod and Cone Photoreceptors 237
The Transduction Channels of Rod and Cone Photoreceptors 237
The Role of CNG Channels in Photoreceptor Physiology 238
The Activation Phase of the Light Response 239
Recovery After a Light Stimulus and Adaptation to Continuous Illumination 240
CNG Channels in the Synaptic Transmission of Cone Photoreceptors 240
The Molecular Composition of CNG Channels 241
The Basic Activation Properties of CNG Channels 242
Transmembrane Topology and Functional Domains 243
The Cyclic-Nucleotide-Binding Domain 243
The Amino Terminal Domain and Modulation by Calmodulin 244
The P Region 244
The GARP Domain of CNGB1 246
CNG Channels are Components of Larger Protein Complexes 246
Modulation by Phosphorylation and All-trans Retinal 247
Synthesis, Maturation, and Targeting of CNG Channels 248
Visual Dysfunction Caused by Mutant CNG Channel Genes 249
References 251
Appendix 255
Visual Dysfunction Caused by Mutant CNG Channel Genes 255
Mutations in CNGA1 and CNGB1 Associated with Retinitis Pigmentosa 256
Mutations in CNGA3 and CNGB3 Associated with Cone Dysfunction 257
References 259
Rhodopsins in Drosophila Color Vision 263
Introduction 263
Anatomy and Molecular Aspects of Color-Sensitive Opsins in the Drosophila Eye 264
Structure of the Drosophila Eye: Ommatidia, Photoreceptors, and Rhodopsins 264
Molecular Genetics and Evolution of Rh5 and Rh6 265
Development and Patterning of Rhodopsins for Drosophila Color Vision 267
Mutually Exclusive Rhodopsin Expression 267
Transcription Factors Specify Outer from Inner Photoreceptors and Distinguish R7 from R8 269
A Stochastic Decision Induces Rhodopsins in R7 Photoreceptor 270
A Bistable Feedback Loop Specifies R8 Photoreceptor Subtype and Expression of Rh5 and Rh6 270
Comparison Between Mammalian and Drosophila Color Vision Rhodopsins 272
Human Color-Sensitive Opsins 272
Photoreceptor and Rhodopsin Specification in Flies and Mammals: Parallel Themes 273
Photoreceptor and Rhodopsin Specification in Flies and Mammals: Different Mechanisms 274
Conclusion 274
References 275
INAD Signaling Complex of Drosophila Photoreceptors 279
Introduction 279
Comparison of Vertebrate and Drosophila Phototransduction Cascades 280
Identification of the INAD Signaling Complex 281
Structure of the INAD Signaling Complex and Binding Specificity 283
Anchoring of the INAD Signaling Complex to the Microvillar Membrane 286
Function of the INAD Signaling Complex 287
Information Transfer From Rhodopsin to the Signaling Complex BY the Visual G Protein 288
Signaling Complexes in Vertebrate Photoreceptor Cells 290
Acknowledgments 292
References 292
Part V: Visual Processing in the Inner Retina 297
Visual Signal Processing in the Inner Retina 299
Introduction 299
Visual Information is First Processed in the OPL 300
Bipolar Cells form Parallel Pathways and Provide Excitatory Input to the IPL 300
Functional Stratification of the IPL 302
ON and OFF Response Stratification 302
Sustained and Transient Response Stratification 303
Synaptic Mechanisms Shape Excitatory Signals in the IPL 303
Glutamate Release Is Tonic and Graded 303
Transporters Terminate Excitatory Signaling to Ganglion Cells 304
Postsynaptic Glutamate Receptor Properties Shape Ganglion Cell Excitation 304
Modulating Glutamate Release Shapes Excitatory Responses 305
Amacrine Cells Mediate Inhibition in the IPL 305
Presynaptic Inhibition 306
Asymmetric Presynaptic Inhibition 306
Presynaptic Inhibition Is Filtered by GABA Receptor Properties 307
Presynaptic Inhibition May Be Shaped by Transmitter Release Differences 307
Glycine, the Other Inhibitory Transmitter 310
Lateral Versus Vertical Inhibitory Pathways in the IPL: The Story of Two Inhibitory Neurotransmitters 310
Parallel Ganglion Cell Output Pathways 311
Ganglion Cells Encode Color Information 311
Directional-Selective Ganglion Cells 312
Intrinsically Photosensitive Ganglion Cells 312
Conclusions 312
References 313
Part VI: Color Vision and Adaptive Processes 317
Human Cone Spectral Sensitivities and Color Vision Deficiencies 319
Introduction 319
Overview 319
Transduction 319
Univariance, Monochromacy, Dichromacy, and Trichromacy 320
Trichromacy and Color-Matching Functions 321
Cone Spectral Sensitivities 322
Introduction 322
Cone Spectral Sensitivity Measurements 322
From Cone Spectral Sensitivities to Color-Matching Functions 325
Other Factors That Influence Spectral Sensitivity 325
Lens Pigment 325
Macular Pigment 326
Photopigment Optical Density 326
Changes with Eccentricity 326
Congenital Color Vision Deficiencies 326
Protan and Deutan Defects 327
Protanopia and Deuteranopia 327
Photopigment Variability and Protanomaly and Deuteranomaly 328
Tritanopia 330
Monochromacies 331
Cone Monochromacies 331
Rod Monochromacy 332
Conclusions 333
Acknowledgment 333
References 333
Luminous Efficiency Functions 341
Introduction 341
The Need for Luminous Efficiency 341
Psychophysical Measures of Luminous Efficiency 344
Factors that Influence Luminous Efficiency 344
Scotopic (Rod) Luminous Efficiency Function 345
Introduction 345
Univariance 345
International Standard 346
Photopic (Cone) Luminous Efficiency Function 346
Introduction 346
International Standards 347
Additive Functions for 2degree Viewing Fields 347
Additive Functions for 10degree Viewing Fields 348
Other Photopic (Nonadditive) Luminous Efficiency Functions 350
Mesopic (Rod-Cone) Luminous Efficiency Functions 351
Introduction 351
Models of Mesopic Luminous Efficiency 351
International Standard 352
Individual Differences Influencing Luminous Efficiency 352
Attenuation of Spectral Light by the Lens and Other Ocular Media 352
Attenuation of Spectral Light by the Macular Pigment 353
Optical Densities of the Photopigments 354
Relative Numbers of L and M Cones 355
Cone Pigment Polymorphisms 355
Directional Sensitivity 356
Variations in the Contribution of Chromatic Channels 356
Conclusions 356
References 357
Cone Pigments and Vision in the Mouse 365
Introduction 365
Prevalence and Spatial Distribution of Mouse Cones 365
Mouse Strain Variations 366
Mouse Cone Pigments 367
Cone Pigment Spectra 367
Evolution and Spectral Tuning of Mouse Cone Pigments 367
Regional Distribution of Mouse Cone Pigments 368
Expression of Mouse Cone Pigments 371
Cone Signal Pathways in the Mouse Retina 371
Cone-Based Vision in Mice 373
Assessment Techniques 373
Spectral Sensitivity 375
Spatial and Temporal Sensitivity 376
Color Vision 377
Alterations in Mouse Vision Consequent to Genetic Manipulations 379
Targeted Deletions of Rods or Cones 379
Addition of New Cone Pigments 380
Mouse and Human Cone Vision 381
Acknowledgment 382
References 382
Multifocal Oscillatory Potentials of the Human Retina 387
Introduction 387
Recording Techniques 387
Underlying Mechanisms 388
The Influence of age and Gender 391
Disease-Related Changes 392
Origins of Single Potentials 392
Dichromats 392
Congenital Stationary Night Blindness 394
Topographical Alterations 394
Diabetes 395
Retinal Vessel Occlusion 397
Glaucoma 397
General Alterations 397
Vigabatrin Treatment 398
Conclusion 399
References 399
Part VII: Aging and Vision 401
The Aging of the Retina 403
Introduction 403
Morphological Alterations 404
Neural Changes 404
Retinal Pigment Epithelium and Lipofuscin Formation 405
Bruch’s Membrane and Choroid 406
Retinal Function Changes 407
Age-Related Macular Disease 407
Conclusions 409
References 410
Aging of the Retinal Pigment Epithelium 415
Introduction 415
Aging Changes In the Fundus 416
Age-Related Changes In RPE Morphology 416
Melanosomes 419
Lipofuscin 419
Pigment Complexes 419
Mitochondria 420
Bruch’s Membrane 420
Functional Consequences of RPE Cell Aging 420
Phagocytic Load 420
The Effect of Lipofuscin on the RPE 420
Melanosomes 422
Antioxidant Capacity of the RPE 422
Lysosomal Enzyme Activity 422
Mitochondrial Damage in the RPE 423
Bruch’s Membrane Aging 424
Oxidative Stress and RPE Aging 424
The Relationship Between Aging and Retinal Pathologies 427
Summary and Conclusions 428
References 428
Visual Transduction and Age-Related Changes in Lipofuscin 433
Introduction: What is Lipofuscin? 433
Lipofuscin of the Retinal Pigment Epithelium 434
Composition of RPE Lipofuscin 435
Fluorescence Properties of RPE Lipofuscin 437
A2E as a Marker of Lipofuscin Accumulation 438
Factors Affecting Accumulation of RPE Lipofuscin 438
Phagocytosis and Autophagy 439
Role of Lysosomal Degradation 440
Role of Oxidative Stress 440
Role of Phototransduction in Accumulation of RPE Lipofuscin 441
Transient Buildup of All-trans Retinal in Photoreceptor Outer Segments as a Critical Factor for Lipofuscin Formation 443
Inhibition of the Retinoid Cycle Inhibits Lipofuscin Accumulation 446
Role of Exposure of the Retina to Light 448
Other Factors Contributing to Accelerated Accumulation of RPE Lipofuscin 449
A Hypothetical Scenario of Biogenesis of RPE Lipofuscin 451
Effects of Lipofuscin on RPE Function and Viability 454
Photoreactivity of RPE Lipofuscin 454
Toxicity of RPE Lipofuscin 457
Effects of Lipofuscin Components and Oxidative Stress in the RPE on Proinflammatory and Angiogenic Signaling 459
Approaches to Diminish Lipofuscin Accumulation or Lipofuscin-Induced Damage 460
Conclusions 462
References 463
Part VIII: Nonphotoreceptor Light Detection and Circadian Rhythms 475
A Nonspecific System Provides Nonphotic Information for the Biological Clock 477
Introduction 477
Nonphotic Information 478
Nonspecific Systems 479
Ascending Reticular-Activating System 479
Orexin/Hypocretin Projection 480
Intergeniculate Leaflet of the Thalamus 483
Anatomy 483
The Pharmacology of the IGL 484
Chronobiology 485
The Electrophysiology of the IGL 485
IGL as an Integrator of Photic and Nonphotic Information 487
Conclusions 487
References 488
The Circadian Clock: Physiology, Genes, and Disease 493
Introduction 493
Circadian Rhythms in Physiology and Behavior 493
Circadian Rhythms in Visual Function 494
Entrainment 495
Anatomy 496
The Suprachiasmatic Nucleus 496
Inputs to the SCN 498
Peripheral Oscillators 499
A Clock in the Eye 499
Oscillators Outside the Nervous System 499
Clock Genes 500
Human Implications 504
Summary 504
References 504
Index 513

Produkt-Details

• Erscheint lt. Verlag: 11.8.2008
• Reihe/Serie: Ophthalmology Research
• Reihe/Serie: Ophthalmology Research
• Zusatzinfo: XI, 509 p.
• Verlagsort: Totowa
• Sprache: englisch
• Themenwelt: Medizin / Pharmazie ► Medizinische Fachgebiete ► Augenheilkunde
• Themenwelt: Naturwissenschaften ► Biologie
• Themenwelt: Technik
• Schlagworte: Cascade • Eye • genes • Molecular Biology • Molecular mechanisms • Non-Visual • Regulation • Transduction • Visual
• ISBN-10: 1-59745-374-9 / 1597453749
• ISBN-13: 978-1-59745-374-5 / 9781597453745