Besharse / Bok The Retina and its Disorders

1. Auflage 2011
ISBN: 978-0-12-382199-7
Verlag: Elsevier Science & Techn.
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 910 Seiten, Web PDF

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

Autoren/Hrsg.

Besharse, Joseph

Bok, Dean

Inhaltsverzeichnis

1;Front Cover;1
2;The Retina and its Disorders;4
3;Copyright Page;5
4;Contributors;6
5;Preface;12
6;Contents;14
7;Acuity;18
7.1;Glossary;18
7.2;Detection and Resolution Acuity;18
7.3;Measurement of Visual Acuity;18
7.4;Reporting Visual Acuity;20
7.5;Optical and Neural Limits on Visual Acuity;20
7.6;Visual Acuity across the Retina;21
7.7;Visual Acuity over Life;21
7.7.1;Visual Standards;21
7.8;Hyperacuity;21
7.9;Dynamic Visual Acuity;22
7.10;Further Reading;22
8;Adaptive Optics;24
8.1;Glossary;24
8.2;The Benefit of Adaptive Optics in Vision Science;24
8.3;Correcting the Eye's Monochromatic Aberration;25
8.4;Vision Correction with AO;26
8.5;Retinal Imaging with AO;26
8.5.1;Compensating for Eye Motion;26
8.5.2;Imaging Cones;28
8.5.3;The Cone Mosaic and Color Vision;28
8.5.4;Imaging Retinal Pigment Epithelium;30
8.5.5;Imaging Retinal Ganglion Cells;31
8.5.6;Imaging Retinal Vasculature;32
8.5.7;Imaging Retinal Disease;32
8.6;Further Reading;33
9;Alternative Visual Cycle in Muumlller Cells;34
9.1;Glossary;34
9.2;Visual Cycle in Retinal Pigment Epithelium Cells;34
9.3;A Role for Muumlller Cells in Visual Pigment Regeneration;34
9.4;A Second Source of Chromophore for Cones;35
9.5;Functional Differences between Rods and Cones;35
9.6;An Alternate Retinoid Isomerase Activity in Cone-Dominant Retinas;36
9.7;11-cis-ROL Dehydrogenase Activity in Cones but Not in Rods;36
9.8;An Alternate Visual Cycle that Mediates Pigment Regeneration in Cones;37
9.9;A New Role for IRBP;37
9.10;Alternate Visual Cycle in Rod-Dominant Species;38
9.11;Further Reading;38
10;Anatomically Separate Rod and Cone Signaling Pathways;39
10.1;Glossary;39
10.2;Rod and Cone Photoreceptors;39
10.3;Cone Postreceptoral Circuitry;39
10.4;Lateral Communication Networks;41
10.4.1;Gap Junctions;41
10.4.2;Horizontal Cells;41
10.4.3;Amacrine Cells;41
10.4.4;Ganglion Cells;42
10.4.5;Multiple Rod Signaling Pathways;42
10.5;Concluding Statements;44
10.6;Acknowledgments;44
10.7;Further Reading;44
11;Anatomy and Regulation of the Optic Nerve Blood Flow;45
11.1;Glossary;45
11.2;Introduction;45
11.3;Anatomy of the Vascular Supply;45
11.3.1;Retina;46
11.3.2;Choroid;47
11.3.3;Optic Nerve;47
11.4;Histology of Blood Vessels in the Optic Nerve;49
11.5;Regulation of Ocular Blood Flow;51
11.6;Technology for Measuring Ocular Blood Flow;52
11.6.1;Color Doppler Imaging;52
11.6.2;Angiography;52
11.6.3;Blue Field Entotpic Technique;53
11.6.4;Laser Doppler Velocimetry;53
11.6.5;Retinal Vessel Diameters;53
11.6.6;Laser Speckle Technique;53
11.6.7;Laser Doppler Flowmetry;53
11.6.8;Pulsatile Ocular Blood Flow;53
11.6.9;Optical Doppler Tomography;54
11.7;Future Studies;54
11.8;Further Reading;54
12;Animal Models of Glaucoma;55
12.1;Glossary;55
12.2;Mammalian Models;55
12.2.1;Primate Models of Glaucoma;55
12.2.2;Rodent Models of Glaucoma;56
12.2.3;Rat Models;56
12.2.4;Mouse Models;57
12.2.4.1;Pressure-induced mouse models;57
12.2.4.2;Normal-tension mouse models;58
12.2.4.3;Developmental mouse models;58
12.2.5;Other Mammalian Models;58
12.3;Nonmammalian Models;59
12.3.1;Zebrafish;59
12.4;Other Nonmammalian Models;59
12.5;Conclusion;59
12.6;Further Reading;59
13;Blood-Retinal Barrier;61
13.1;Glossary;61
13.2;Blood-Retinal Barrier;61
13.2.1;Inner Blood-Retinal Barrier;62
13.2.1.1;Retinal endothelial cells;62
13.2.1.2;Retinal endothelial TJs;63
13.2.1.3;Muumlller cells, astrocytes, and pericytes;63
13.2.2;Outer Blood-Retinal Barrier;64
13.2.2.1;RPE cells;64
13.2.2.2;RPE tight junctions;64
13.2.2.3;Polarity of the outer and inner barriers: TJ modulation;64
13.2.2.4;Other factors regulating the molecular movement in the eye;64
13.2.3;The Blood-Retinal Barrier and Ocular Immune Privilege;65
13.2.3.1;Clinical evaluation of the blood-retinal barrier;65
13.2.3.2;Blood-retinal barrier and macular edema;66
13.2.4;Relevance of BRB to Treatment of Retinal Diseases;66
13.3;Further Reading;67
14;Breakdown of the Blood-Retinal Barrier;68
14.1;Glossary;68
14.2;Introduction;68
14.3;Tight Junctions;68
14.4;Vesicular Transport;69
14.5;Role of Inflammation;69
14.6;Molecular Mechanisms;70
14.7;Assessing BRB Breakdown;71
14.8;Inhibiting BRB Breakdown;72
14.9;Prospects for the Future;73
14.10;Conclusions;73
14.11;Acknowledgments;73
14.12;Further Reading;73
15;Breakdown of the RPE Blood-Retinal Barrier;75
15.1;Glossary;75
15.2;Introduction;75
15.3;RPE Barrier Structure;75
15.4;RPE Barrier Functions;76
15.5;Transport and Fluid Flow within the RPE and Eye;76
15.6;RPE Na,K-ATPase pump;77
15.7;Methods to Assess RPE Barrier Structure and Function;77
15.7.1;Tight Junction Structure;77
15.7.2;Barrier Function;77
15.7.3;Assays That Measure Barrier Properties of RPE;77
15.8;Clinical Conditions Associated with Breakdown of the RPE Barrier;78
15.8.1;Inflammation/Infection;79
15.8.2;Age-Related Macular Degeneration;79
15.8.3;Diabetes Mellitus;81
15.8.4;Proliferative Vitreoretinopathy;81
15.8.5;Drug Toxicity;81
15.8.6;Central Serous Retinopathy;82
15.8.7;Retinitis Pigmentosa;83
15.8.8;Growth Factors;83
15.9;Studies to Increase the Function of the BRB;84
15.10;Further Reading;84
16;Circadian Metabolism in the Chick Retina;85
16.1;Glossary;85
16.2;Introduction;85
16.3;Clock Gene Expression;85
16.4;Circadian Regulation of Cyclic AMP in Retina;86
16.5;Circadian Regulation of Melatonin Biosynthesis;88
16.6;Other Rhythms of Gene Expression and Metabolism in the Chick Retina;90
16.7;Conclusion;91
16.8;Acknowledgments;91
16.9;Further Reading;91
17;Central Retinal Vein Occlusion;92
17.1;Glossary;92
17.2;Pathogenesis;92
17.3;Site of Occlusion in CRVO;93
17.4;Demographic Characteristics;93
17.5;Clinical Features;94
17.6;Differentiation of Ischemic from Nonischemic CRVO;95
17.7;Course of CRVO;96
17.7.1;Complications;96
17.8;Management of CRVO;98
17.8.1;Medical Treatments;99
17.8.2;Surgical or Invasive Treatments;99
17.8.3;Panretinal Photocoagulation;100
17.8.4;Primary Factor Responsible for Blindness in Ischemic CRVO with Neovascular Glaucoma;102
17.9;Overall Conclusions About Advocated Treatments for CRVO;102
17.9.1;Natural History of Visual Outcome in CRVO;102
17.9.2;Investigations of CRVO Patients;102
17.10;Further Reading;103
18;Choroidal Neovascularization;104
18.1;Glossary;104
18.2;Choroidal Neovascularization;104
18.2.1;Clinical Detection of CNV;104
18.2.2;Histopathology of CNV;106
18.2.3;Animal Models of CNV;107
18.2.3.1;Laser-induced CNV;107
18.2.3.2;Growth factor models;107
18.2.4;Pathobiology of CNV;108
18.2.4.1;Angiogenesis;108
18.2.4.1.1;Vascular endothelial growth factor;108
18.2.4.1.2;Other angiogenic factors;108
18.2.4.1.3;Natural inhibitors of angiogenesis;108
18.2.4.1.3.1;Inflammation;108
18.2.4.1.3.2;Monocytes and macrophages;108
18.2.4.1.3.3;Complement;109
18.2.4.1.3.4;Vasculogenesis;109
18.2.5;Therapy of CNV;109
18.2.6;Variants of Pathologic Neovascularization in NVAMD;110
18.2.6.1;Polypoidal choroidal vasculopathy;110
18.2.6.2;Retinal angiomatous proliferation;111
18.3;Future Directions;112
18.4;Further Reading;112
19;Chromatic Function of the Cones;113
19.1;Glossary;113
19.2;Introduction;113
19.3;Photopigments and Phototransduction;114
19.4;Fundamental Spectral Sensitivities;114
19.5;Prereceptoral Attenuation;115
19.6;Cone Spectral Sensitivities;115
19.6.1;Template for Cone Spectral Sensitivity;116
19.6.2;Cone Gains and von Kries Scaling;116
19.7;Isolating Cone Responses;116
19.7.1;Selective Chromatic Adaptation;117
19.7.2;Silent Substitution;117
19.7.3;Rod Intrusion;118
19.8;Spatial Densities;118
19.8.1;Individual Variations;118
19.8.2;Retinal Distributions;118
19.8.3;Eccentricity and Chromatic Function;119
19.9;Postreceptoral Spectra;119
19.9.1;Cone Opponency;119
19.9.2;Advantages of Cone Opponency;119
19.10;Further Reading;120
20;The Circadian Clock in the Retina Regulates Rod and Cone Pathways;122
20.1;Glossary;122
20.2;Introduction;122
20.3;Rod and Cone Pathways in the Fish Retina;123
20.4;Day/Night Differences in the Light Responses of Neurons in the Fish Outer Retina;124
20.5;The Circadian Clock in the Retina, and Not the Retinal Response to the Ambient Illumination, Controls Rod-Cone Coupling;125
20.6;The Circadian Clock in the Mammalian Retina Controls Rod-Cone Coupling;126
20.7;A Circadian Clock Pathway in the Retina;126
20.8;Functional Implications of Circadian Clock Control of Rod-Cone Coupling;127
20.9;Further Reading;128
21;Circadian Photoreception;129
21.1;Glossary;129
21.2;Introduction;129
21.3;Nonvisual Photoreception;129
21.4;Melanopsin and the Mammalian ipRGC;131
21.5;Functions of ipRGCs;132
21.6;Further Reading;134
22;Circadian Regulation of Ion Channels in Photoreceptors;135
22.1;Glossary;135
22.2;Circadian Oscillators Regulate the Functions of the Visual System;135
22.3;Circadian Regulation of Photoreceptors;135
22.4;Ion Channels in Photoreceptors;136
22.5;Circadian Regulation of cGMP-gated Cation Channels;136
22.5.1;Signaling Pathways Leading to the Circadian Regulation of CNGCs;137
22.5.2;Circadian Phase-Dependent Modulation of Cone CNGCs by Dopamine;137
22.5.3;Modulation of Cone CNGCs by Somatostatin;138
22.6;Circadian Regulation of L-VGCCs;138
22.7;Circadian Regulation of Other Photoreceptor Ion Channels: Potassium Channels (K+ Channels);139
22.8;Conclusion;139
22.9;Further Reading;140
23;Circadian Rhythms in the Fly's Visual System;141
23.1;Glossary;141
23.2;The Fly's Visual System;141
23.3;The Fly's Circadian System;143
23.4;Circadian Rhythms in the Retina of the Compound Eye;144
23.5;Circadian Rhythms in the First Visual Neuropil (Lamina);146
23.5.1;Circadian Plasticity of Synaptic Contacts;146
23.5.2;Circadian Plasticity of Second-Order Neurons and Glial Cells;147
23.5.3;Circadian Rhythms in Organelles inside Photoreceptor Terminals;148
23.6;Neurotransmitter Regulation of Circadian Rhythms in the Visual System;148
23.7;Larval Visual System;149
23.8;Circadian Circuits in the Fly's Visual System;149
23.9;The Role of Circadian Clocks in the Visual System;149
23.10;Further Reading;150
23.11;Relevant Websites;150
24;Color Blindness: Acquired;151
24.1;Glossary;151
24.2;Introduction;151
24.3;Classifying Acquired Color Blindness;151
24.4;Discriminating Acquired from Inherited Color Blindness;152
24.5;Conditions Resulting in an Acquired Color-Vision Defect;153
24.5.1;Ocular Diseases;153
24.5.1.1;Age-related macular degeneration;153
24.5.1.2;Glaucoma;153
24.5.1.3;Retinitis pigmentosa;153
24.5.1.4;Cataract;154
24.5.1.5;Diabetic retinopathy;154
24.5.1.6;Optic neuritis;154
24.5.2;Cortical Defects;154
24.5.2.1;Cerebral achromatopsia;154
24.5.2.2;Neurodegenerative diseases;154
24.5.3;Toxin-Induced Defects;155
24.5.3.1;Digitalis;155
24.5.3.2;PDE5 inhibitors;155
24.5.3.3;Chloroquine;155
24.5.3.4;Ethambutol;155
24.5.3.5;Vitamin A deficiency;156
24.5.3.6;Exposure to metals and chemicals;156
24.6;Conclusion;156
24.7;Further Reading;156
25;Color Blindness: Inherited;157
25.1;Glossary;157
25.2;Introduction;157
25.3;Photoreceptor Basis of Human Color Vision;157
25.4;Genetic Basis of Human Color Vision;158
25.5;Red-Green Color-Vision Deficiencies;160
25.6;Tritan Color-Vision Deficiencies;161
25.7;Blue-Cone Monochromacy;163
25.8;Achromatopsia;163
25.9;Conclusion;163
25.10;Further Reading;164
26;The Colorful Visual World of Butterflies;165
26.1;Glossary;165
26.2;Introduction;165
26.3;The Butterflies and Their Evolutionary History;165
26.4;Color Vision and the Butterfly Eye;166
26.5;Spectral Heterogeneity of Butterfly Eyes;167
26.6;Diversification of Visual Pigments via Gene Duplication and Positive Selection;168
26.7;Diversification of Photoreceptor Types via Filtering Pigments;170
26.8;Evolution of Sexually Dimorphic Eyes: Opsin Duplications and Sex-Specific Filtering Pigment Expression;171
26.9;Ecological Significance of Butterfly Visual System Diversity;171
26.10;Conclusions;172
26.11;Further Reading;172
27;Cone Photoreceptor Cells: Soma and Synapse;173
27.1;Glossary;173
27.2;Introduction;173
27.3;Structure;173
27.3.1;Morphology and Topology;173
27.3.2;Axon and Terminal;173
27.3.3;Synapse;175
27.3.4;Invagination and Triad;175
27.3.5;Biophysical Properties;175
27.3.6;Gap Junctions;176
27.3.7;Morphological Implications of Spectral Sensitivity;176
27.4;Function;176
27.4.1;Adaptation and Predictive Coding;176
27.4.2;Synaptic Transfer Function;176
27.4.3;Rate of Vesicle Release;177
27.4.4;Electrical Coupling;177
27.4.5;Negative Feedback;178
27.5;Theory of Ephaptic Feedback;178
27.5.1;Bandpass Adaptation Filter;179
27.6;Conclusion;179
27.7;Acknowledgments;179
27.8;Further Reading;179
28;Contrast Sensitivity;180
28.1;Glossary;180
28.2;Contrast-Detection Threshold;180
28.3;Psychophysical Assessment of Vision;180
28.4;Spatial Frequency Channels;181
28.5;Contrast Sensitivity Function;182
28.6;Temporal Contrast Sensitivity;183
28.7;Further Reading;185
29;Coordinating Division and Differentiation in Retinal Development;186
29.1;Glossary;186
29.2;Introduction;186
29.3;A Few Basics of Cell-Cycle Regulation;187
29.4;Cyclins and Cdks in Retinal Development;189
29.5;The Rb Family in Retinal Development;190
29.6;Ink4 CKIs and p19Arf in Retinal Development;191
29.7;Cip/Kip CKIs in Retinal Development;191
29.8;E2Fs in Retinal Development;192
29.9;Separating Rate, Birth, and Exit;192
29.10;Distance from Notch Predicts Birth;192
29.11;Birth Does Not Require Exit;193
29.12;Mechanisms Linking Birth to Exit;194
29.13;Conclusion;194
29.14;Acknowledgments;195
29.15;Further Reading;195
30;Developmental Anatomy of the Retinal and Choroidal Vasculature;196
30.1;Glossary;196
30.2;Choroidal Vascular Network;196
30.2.1;Embryology;196
30.2.2;Gross Anatomy;196
30.2.3;Physiology;199
30.2.4;Pathology;199
30.3;Hyaloid Vascular Network;199
30.3.1;Embryology;199
30.3.2;Physiology;200
30.3.3;Pathology;200
30.4;Retinal Vascular Network;200
30.4.1;Embryology;200
30.4.2;Gross Anatomy;200
30.4.3;Physiology;201
30.4.4;Pathology;202
30.5;Further Reading;202
31;Development of the Retinal Vasculature;203
31.1;Glossary;203
31.2;Introduction;203
31.3;An Overview of Human Adult Retinal Vasculature;203
31.3.1;Vasculature of the Primordial Retina;203
31.3.2;Formation of the Human Retinal Vasculature Takes Place Through Vasculogenesis and Angiogenesis;205
31.3.2.1;Vasculogenesis: Vascular formation through transformation from VPCs;205
31.3.3;Lack of Involvement of VEGF in Early Stages of Vascularization;210
31.3.3.1;Angiogenic and anti-angiogenic factors;212
31.3.4;Cell-Cell Interactions in the Formation of the Human Retinal Vasculature;212
31.3.4.1;Muumlller cell-endothelial cell interactions;212
31.3.4.2;Pericyte-endothelial cell interactions: Vessel stability;212
31.3.5;Vascular Remodeling;212
31.3.6;Vascularization and the Health of the Eye;213
31.4;Conclusions;213
31.5;Further Reading;213
32;Embryology and Early Patterning;215
32.1;Glossary;215
32.2;Embryology;215
32.3;Early Patterning;217
32.3.1;Proximo-Distal Patterning of the Optic Vesicle;217
32.3.2;Specification of the RPE and NR;219
32.3.3;Dorso-Ventral Patterning of the Optic Cup;220
32.4;Conclusions;220
32.5;Further Reading;221
32.6;Relevant Website;221
33;Evolution of Opsins;222
33.1;Glossary;222
33.2;Introduction;223
33.3;General Opsin Structure and Function;223
33.4;Type I and Type II Opsins;223
33.5;Major Type II Opsin Classes;223
33.5.1;Cnidops;223
33.5.2;Retinal G-Protein Receptor/Go;225
33.5.3;Rhabdomeric (Gq);225
33.5.4;Ciliary (Gt);225
33.6;Opsin and Color Vision;225
33.7;Molecular Basis of Wavelength Sensitivity;227
33.8;Opsin and Modes of Phototransduction Evolution;227
33.9;Further Reading;227
34;Eye Field Transcription Factors;229
34.1;Glossary;229
34.2;Discovery and Structural Features of Eye- Field Transcription Factors;229
34.2.1;Pax6;229
34.2.2;Six3;229
34.2.3;Six6;229
34.2.4;Rax;230
34.2.5;Lhx2;230
34.2.6;Tbx3;230
34.2.7;Nr2e1;230
34.3;The EFTFs are Expressed during and are Required for Normal Eye Formation;231
34.4;The EFTFs Form a Self-Sustaining Feedback Network;233
34.5;The Coordinated Expression of EFTFs is Sufficient for Eye Formation;233
34.6;Conclusions;235
34.7;Further Reading;235
35;Fish Retinomotor Movements;236
35.1;Glossary;236
35.2;Nature and Occurrence;236
35.3;Mechanisms of Force Production for Retinomotor Movements;237
35.3.1;Force Production for Photoreceptor Elongation and Contraction;237
35.3.2;The RPE Cytoskeleton and Force Production for Pigment Granule Dispersion and Aggregation;238
35.4;Intracellular Regulation of Retinomotor Movements: The Role of Cyclic Adenosine Monophosphate;239
35.5;Regulation of Photoreceptor Retinomotor Movements by Paracrine Messenger;240
35.5.1;Dopamine;240
35.5.2;Adenosine;242
35.6;Regulation of Retinomotor Movements in RPE Cells by Paracrine Messengers;242
35.7;Functions and Significance of Retinomotor Movements;243
35.8;Summary;243
35.9;Further Reading;244
36;GABA Receptors in the Retina;245
36.1;Glossary;245
36.2;Introduction;245
36.3;Vesicular Transporters;245
36.4;Plasma Membrane Transporters;246
36.4.1;Neuronal Localization;247
36.4.2;Function;248
36.5;Synaptic Receptors;248
36.5.1;Photoreceptors;249
36.5.2;Horizontal Cells;249
36.5.3;Bipolar Cells;249
36.5.4;Amacrine Cells and Ganglion Cells;250
36.5.5;Muumlller's Cells;251
36.6;Further Reading;251
36.7;Relevant Website;251
37;Ganglion Cell Development: Early Steps/Fate;252
37.1;Glossary;252
37.2;Retinal Ganglion Cell Formation;252
37.3;Atoh7/Ath5 Function is Critical for RGC Development;252
37.4;Integrated Regulation of Atoh7/Ath5 Retinal Expression;253
37.5;Atoh7/Ath5 Activates Pou4f/Brn3 Expression in RGCs;254
37.6;Pou4f2/Brn3b Controls Numerous RGC Processes;255
37.7;Islet1 Acts Parallel to Pou4f2 During RGC Development;255
37.8;Conclusion;256
37.9;Further Reading;256
38;Genetic Dissection of Invertebrate Phototransduction;257
38.1;Glossary;257
38.2;The Drosophila Phototransduction Cascade;259
38.2.1;Genetic Screens for Mutants Defective in Phototransduction Proteins;259
38.3;The Photochemical Cycle and the Mechanism Underlying Termination of M Activity;259
38.4;Coupling of Photoexcited R to Inositol Phospholipid Hydrolysis;261
38.4.1;Light-Activated Gq Protein;261
38.4.2;Light-Activated PLC;262
38.5;The TRP Channels;262
38.5.1;The trp Mutant and the Discovery of the TRP Channel;262
38.6;Biophysical Properties of the TRP Channel;262
38.7;Lipids Activate the Light-Sensitive Channels in the Dark;265
38.8;Organization in a Supramolecular Signaling Complex via the Scaffold Protein Inactivation No Afterpotential D;266
38.9;The Photoreceptor Cells Are Sensitive to Single Photons;267
38.10;Conclusions;268
38.11;Further Reading;268
38.12;Relevant Website;268
39;Hereditary Vitreoretinopathies;269
39.1;Glossary;269
39.2;Introduction;269
39.3;Classification of the Hereditary Vitreoretinopathies;269
39.4;Clinical Features of the Hereditary Vitreoretinopathies;269
39.4.1;Vitreoretinopathies Associated with Skeletal Abnormalities;269
39.4.1.1;Stickler syndrome (OMIM #108300, #604841, and #184840);269
39.4.1.2;Kniest dysplasia (OMIM #156550);270
39.4.1.3;Spondyloepiphyseal dysplasia congenital (OMIM #183900);270
39.4.1.4;Marshall syndrome (OMIM #154780);270
39.4.1.5;Knobloch syndrome (OMIM #267750);273
39.4.1.6;Marfan syndrome (OMIM #154700);273
39.4.2;Vitreoretinopathies Associated with Progressive Retinal Dysfunction;274
39.4.2.1;Wagner syndrome (OMIM #143200);274
39.4.2.2;Goldmann-Favre syndrome/enhanced S-cone dystrophy (OMIM #268100);275
39.4.3;Vitreoretinopathies Associated with Abnormal Retinal Vasculature;275
39.4.3.1;Familial exudative vitreoretinopathy (OMIM #133780, #601813, and #305390);276
39.4.3.2;Autosomal dominant vitreochoroidopathy (OMIM #193220);276
39.4.4;Vitreoretinopathy Associated with Corneal Changes;276
39.4.4.1;Snowflake vitreoretinal degeneration (OMIM #193230);277
39.5;Molecular Genetics of the Hereditary Vitreoretinopathies;277
39.6;Further Reading;279
39.7;Relevant Website;279
40;Histogenesis: Cell Fate: Signaling Factors;280
40.1;Glossary;280
40.2;Introduction;280
40.3;Notch;280
40.4;The Wnt Pathway;281
40.5;The Hedgehog Signaling Pathway;282
40.6;Transforming Growth Factor-beta;283
40.7;Signaling Molecules and Photoreceptor Development;285
40.8;Conclusion;286
40.9;Further Reading;286
41;Immunobiology of Age-Related Macular Degeneration;287
41.1;Glossary;287
41.2;Epidemiology and Clinical Findings of Age-Related Macular Degeneration;287
41.3;The Immune System in AMD;288
41.3.1;Histopathology of Drusen;288
41.3.2;Role of Macrophages;288
41.3.3;Adaptive Immune System;289
41.3.4;Infectious Agents;289
41.4;Genetics of AMD and Evidence for a Role of Inflammation in the Pathogenesis of AMD;289
41.5;Mouse Models of AMD;290
41.6;Summary;291
41.7;Further Reading;292
42;Information Processing: Amacrine Cells;293
42.1;Glossary;293
42.2;Amacrine Cells;293
42.3;AC Classification, Form, and Patterns;293
42.4;AC Synapses and Neurochemistry;295
42.5;ACs and Signal-Processing Fundamentals;296
42.6;Examples of AC Networks;297
42.6.1;gamma ACs of the Rod Pathway;297
42.6.2;Gly ACs of the Rod Pathway;298
42.6.3;Small gamma ACs of the Primate Midget BC rarr GC Pathway;298
42.6.4;gamma ACs of the Directionally Selective GC pathway;299
42.7;Axonal Cells;299
42.8;ACs and Disease;300
42.9;Further Reading;300
43;Information Processing: Bipolar Cells;301
43.1;Glossary;301
43.2;Further Reading;306
44;Information Processing: Contrast Sensitivity;307
44.1;Glossary;307
44.2;Contrast Processing and Adaptation;307
44.3;The Spatial Receptive Field;307
44.4;The Temporal Receptive Field;308
44.5;Receptive Field Properties Explain Contrast Sensitivity Functions;309
44.6;Disrupting Specific Retinal Pathways Alters Perceptual Contrast Sensitivity in Selective Ways;309
44.7;Physical Limits to Contrast Sensitivity;310
44.8;Further Reading;311
45;Information Processing: Direction Sensitivity;312
45.1;Glossary;312
45.2;Physiological Functions of DSGCs;312
45.3;Synaptic Circuitry of DSGCs;313
45.4;Direction-Selective Responses in SAC Processes;315
45.5;Integration of Multiple Cooperative Mechanisms for Direction Selectivity;316
45.6;Concluding Remarks;316
45.7;Acknowledgments;316
45.8;Further Reading;317
46;Information Processing: Ganglion Cells;318
46.1;Glossary;318
46.2;Ganglion Cell Types;318
46.3;Principles of Ganglion Cell Processing;318
46.4;Temporal Processing;318
46.5;Spatial Processing;319
46.5.1;Center-Surround Receptive Fields;319
46.5.2;Tiling;319
46.6;Stimulus Features that Trigger Ganglion Cell Activity;321
46.6.1;Ganglion Cells as Spatiotemporal Filters;321
46.6.2;Ganglion Cells as Specific Feature Detectors;321
46.6.2.1;Direction-selective (DS) ganglion cells;322
46.6.2.2;Object motion sensitive (OMS) ganglion cells;323
46.6.2.3;Saccadic suppression;324
46.6.2.4;Approach-sensitive ganglion cells;324
46.7;Further Reading;325
47;Information Processing: Horizontal Cells;326
47.1;Glossary;326
47.2;Introduction;326
47.2.1;Synaptic Interactions and Gap-Junction Coupling of Horizontal Cell Subclasses;327
47.2.2;Ionic Conductances of Horizontal Cells and the Response to Light;328
47.3;Cellular Mechanisms of Horizontal Cell Neurotransmission;329
47.3.1;Horizontal Cell Feedback and Feed-Forward;329
47.3.2;Feed-Forward onto Bipolar Cell Dendrites;330
47.3.3;Feedback onto Photoreceptor Terminals;330
47.3.4;Ephaptic Transmission between Horizontal Cells and Photoreceptor Terminals;331
47.3.5;Proton Mediation of Horizontal Cell Feedback;331
47.4;Functional Roles of Horizontal Cells;331
47.4.1;Retinal Adaptation;331
47.4.2;Gain Control of Synapses in the Outer Retina;332
47.4.3;Spatial and Temporal Processing;333
47.4.4;Chromatic Processing;333
47.5;Conclusions;334
47.6;Acknowledgments;334
47.7;Further Reading;334
48;Information Processing in the Retina;335
48.1;Glossary;335
48.2;Introduction;335
48.3;The Outer Retina, Gain and Level Adjustment;335
48.4;Bifurcation of the Visual Pathways into ON and OFF streams;336
48.5;Horizontal Cell Synaptic Interactions;336
48.6;Horizontal Cells and Local Gain Control;336
48.7;Interactions at the Inner Retina: Contrast Gain;337
48.8;General Organizational Principles;337
48.8.1;Lateral Interactions are Concatenated;337
48.8.2;Mutual Antagonism is a Form of Amplification;337
48.8.3;Redundant Feedforward and Feedback Interactions;337
48.8.4;Interaction between the Two Complementary Visual Streams in the Visual System;337
48.9;Inner Retinal Processing: Circuitry for Feature Extraction;338
48.9.1;Amacrine Cell Morphological Types;339
48.9.2;Specific Ganglion Cell Circuitries;339
48.9.2.1;Directional selectivity;339
48.10;Functions of AII Amacrine Cells;340
48.11;Further Reading;341
49;Information Processing: Retinal Adaptation;342
49.1;Glossary;342
49.2;Light Adaptation;343
49.2.1;Characteristics of Light Adaptation;343
49.2.2;Mechanisms and Sites of Light Adaptation;345
49.3;Contrast Adaptation;346
49.4;Chromatic Adaptation;347
49.5;Dark Adaptation;347
49.5.1;Characteristics of Dark Adaptation;348
49.5.2;Mechanisms of Dark Adaptation;349
49.6;Conclusion;349
49.7;Further Reading;349
49.8;Relevant Websites;349
50;Optic Nerve: Inherited Optic Neuropathies;350
50.1;Glossary;350
50.2;Leber's Hereditary Optic Neuropathy;350
50.3;Dominant Optic Atrophy (DOA);352
50.4;Recessive Optic Atrophy;352
50.5;Other Inherited Conditions with Optic Atrophy;353
50.6;Conclusion;353
50.7;Further Reading;354
51;Injury and Repair: Light Damage;355
51.1;Glossary;355
51.2;Introduction;355
51.3;Role of Rhodopsin Activation in Light Damage;356
51.4;Mechanisms of Photic Injury: From Gene Expression to the Molecular Pathway;357
51.4.1;Apoptosis Genes;358
51.4.2;Role of Oxidant Stress in Light Damage;358
51.4.3;Role of Inflammation in Light Damage;358
51.4.4;Tissue Remodeling;359
51.4.5;Transcription Factors;359
51.5;Identification of Two Nonredundant Mechanisms of Endogenous Protection of Photoreceptors;359
51.5.1;Rhodopsin-Activated Endogenous Protection;360
51.5.2;Identification of Mechanisms for Chronic Light Stress-Induced Endogenous Protection;360
51.5.3;Role of Leukemia Inhibitory Factor;360
51.6;Concluding Remarks;361
51.7;Further Reading;361
52;Injury and Repair: Neovascularization;363
52.1;Glossary;363
52.2;Introduction;363
52.3;Mechanisms of Injury;363
52.4;Animal Models of NV after Laser- Induced Injury;365
52.5;Acute Responses to Retinal Injury;365
52.5.1;Blood-Retina Barrier Breakdown;365
52.5.2;Acute Release of Cytokines;365
52.5.3;Injury-Induced Complement Activation;367
52.5.4;Other Angiogenic Mediators in the Retinal Response to Injury;367
52.5.5;Modulation of the Extracellular Matrix;367
52.6;Cellular Response in Injury-Induced NV;367
52.6.1;Neutrophils;368
52.6.2;Macrophages;368
52.6.3;Progenitor/Stem Cells;368
52.6.4;Other Infiltrating Cell Types;368
52.6.5;Resident Tissue Cells;368
52.6.5.1;Microglia;369
52.6.5.2;Retinal astrocytes;369
52.6.5.3;Muumlller cells;369
52.6.6;Cellular Responses to VEGF-A Receptor Binding;369
52.7;Conclusion;369
52.8;Further Reading;370
53;Injury and Repair: Prostheses;371
53.1;Glossary;371
53.2;Rationale for a Prosthetic Device;371
53.3;Brain Prosthetic Devices;371
53.4;Retinal Prosthetic Devices;372
53.5;Clinical Trials;373
53.6;Challenges;374
53.7;Future Prospects;375
53.8;Further Reading;375
54;Injury and Repair: Retinal Remodeling;377
54.1;Glossary;377
54.2;Overview;377
54.3;Progression;377
54.3.1;Phase 1;378
54.3.2;Phase 2;378
54.3.3;Phase 2+;379
54.3.4;Phase 3;379
54.4;Remodeling Events;379
54.4.1;Reprogramming;379
54.4.2;Rewiring;380
54.4.3;Neuritogenesis;380
54.4.4;Synaptogenesis and Microneuromas;380
54.4.5;Self-Signaling;380
54.4.6;Migration;380
54.4.7;Cell Death;381
54.4.8;MC Remodeling;381
54.4.9;RPE Remodeling;381
54.4.10;Vascular Remodeling;381
54.5;Impact of Remodeling on Therapeutics;381
54.5.1;Primary Gene Therapy;381
54.5.2;Survival Factor Therapy;382
54.5.3;Stem/Neuroprogenitor Cell Therapy;382
54.5.4;Retinal Transplantation;382
54.5.5;Secondary Gene Therapies: Photosensitive Proteins;382
54.5.6;Bionic Implants;382
54.6;The Importance of Cone Rescue;383
54.7;Further Reading;383
55;Injury and Repair: Stem Cells and Transplantation;384
55.1;Glossary;384
55.2;Introduction;384
55.3;Early Transplant Work;384
55.4;Neural Progenitor Cells;384
55.5;Retinal Progenitor Cells;385
55.6;Induced Pluripotent Stem Cells;385
55.7;Stem Cells for Neuroprotection;386
55.8;Retinal Transplantation;386
55.9;Transplantation Strategies;387
55.10;Polymer Substrates;387
55.11;Inhibitory Barriers;388
55.12;Conclusions;390
55.13;Further Reading;390
55.14;Relevant Websites;390
56;Innate Immune System and the Eye;391
56.1;Glossary;391
56.2;Introduction;391
56.3;Passive Innate Defense System;391
56.3.1;Anatomic and Physical Barriers;391
56.3.1.1;Eyelids and eyelashes;391
56.3.1.2;Tear film;391
56.3.1.3;Corneal epithelium;392
56.3.1.4;Posterior lens capsule;392
56.3.1.5;Retinal pigment epithelium;392
56.3.2;Chemical Barriers;393
56.3.2.1;Lysozyme;393
56.3.2.2;Secretory phospholipase A2;393
56.3.2.3;Cathelicidin (LL-37);393
56.3.2.4;Defensins;393
56.3.2.5;Lactoferrin;394
56.3.2.6;Lipocalin-A;394
56.3.2.7;Secretory IgA;394
56.3.2.8;Complement;394
56.4;Active Innate Defense System;394
56.4.1;Pattern Recognition Receptors;394
56.4.1.1;Toll-like receptors;394
56.4.1.2;NOD-like receptors;394
56.4.1.3;Complement;395
56.4.2;Cytokines, Chemokines, and Effector Cells;396
56.4.2.1;Initiation and amplification;396
56.4.2.2;Clearing the pathogen;396
56.4.3;Innate Immune Privilege;396
56.4.4;Link between Innate and Adaptive Immunity;396
56.5;Conclusion;397
56.6;Further Reading;397
57;IOP and Damage of ON Axons;398
57.1;Glossary;398
57.2;Introduction - Intraocular Pressure as a Risk Factor for Glaucoma;398
57.3;Biomechanical Engineering Studies;399
57.4;Modulation of Glia Behavior at the Optic Nerve Head and Dysfunction of Ganglion Cell Axons;399
57.5;Compartmentalized Self-Destruct Pathways and the Pathology of Glaucoma;403
57.6;Acknowledgments;404
57.7;Further Reading;404
58;Intraretinal Circuit Formation;406
58.1;Introduction;406
58.2;Organization of Retinal Circuits of Vertebrates;406
58.3;Formation of Retinal Synaptic Laminae;406
58.4;Assembly of the Vertical Pathway;406
58.4.1;Retinal Ganglion Cells;408
58.4.2;Bipolar Cells;409
58.4.3;Photoreceptors;410
58.4.4;Synaptogenesis in the Vertical Pathway;410
58.5;Assembly of Lateral Circuits;412
58.5.1;Inner Retina - Amacrine Cells;412
58.5.2;Outer Retina - Horizontal Cells;413
58.6;Emergence of Function - Spontaneous and Light-Evoked Activity;413
58.7;Conclusions;414
58.8;Further Reading;415
59;Ischemic Optic Neuropathy;416
59.1;Glossary;416
59.2;Classification;416
59.3;Nonarteritic Anterior Ischemic Optic Neuropathy;416
59.3.1;Pathogenesis;416
59.3.2;Risk Factors for Development of NA-AION;416
59.3.2.1;Conclusion;418
59.3.3;Clinical Features of NA-AION;418
59.3.3.1;Bilateral NA-AION;419
59.3.3.2;Recurrence of NA-AION in the same eye;420
59.3.3.3;NA-AION and phosphodiesterase-5 inhibitors;420
59.3.3.4;Amiodarone and NA-AION;420
59.3.3.5;Familial NA-AION;420
59.4;Management of NA-AION;420
59.5;Incipient NA-ION;422
59.6;Arteritic AION;422
59.6.1;Pathogenesis;422
59.6.2;Clinical Features of GCA and A-AION;422
59.6.2.1;Symptoms;422
59.6.2.2;Signs;422
59.6.2.3;Laboratory investigations;422
59.7;Management of A-AION;423
59.8;Differentiation of A-AION from NA-AION;424
59.8.1;Steroid Therapy to Prevent Blindness in GCA;424
59.8.1.1;Conclusion;424
59.9;Posterior Ischemic Optic Neuropathy;425
59.9.1;Classification;425
59.9.2;Pathogenesis;425
59.9.2.1;Arteritic PION;425
59.9.2.2;Nonarteritic PION;425
59.9.2.3;Surgical PION;425
59.9.3;Clinical Features of PION;426
59.9.3.1;Symptoms;426
59.9.3.2;Signs;426
59.9.4;Management of PION;427
59.9.4.1;Arteritic PION;427
59.9.4.2;Nonarteritic PION;427
59.9.4.3;Surgical PION;427
59.10;Conclusions;427
59.11;Further Reading;427
60;Light-Driven Translocation of Signaling Proteins in Vertebrate Photoreceptors;429
60.1;Glossary;429
60.2;Introduction;429
60.3;Light Dependency of Protein Translocation;429
60.4;Hypotheses on the Functional Roles of Protein Translocation;430
60.5;What Is the Mode of Protein Translocation: Active Transport or Diffusion?;430
60.6;Specific Mechanisms of Protein Translocation;431
60.6.1;Transducin;431
60.6.2;Arrestin;432
60.6.3;Proteins' Return in the Dark;432
60.7;Further Reading;432
61;Limulus Eyes and Their Circadian Regulation;433
61.1;Glossary;433
61.2;Organization of the Limulus Visual System;433
61.2.1;Lateral Compound Eyes;433
61.2.2;Median Eyes;435
61.2.3;Rudimentary Eyes;435
61.2.4;The Photoreceptors;436
61.2.5;Circadian Organization of the Limulus Visual System;437
61.3;Effects of the Clock on Limulus Eyes;437
61.3.1;Structure;437
61.3.2;Physiology;438
61.3.3;Rhabdom Shedding;439
61.3.4;Gene Expression;439
61.4;Biochemical Processes Mediating Clock Effects on Limulus Eyes;440
61.4.1;Octopamine and the Activation of a cAMP Cascade;440
61.4.2;Clock-Driven Protein Phosphorylation;440
61.5;Conclusion;441
61.6;Further Reading;441
62;Macular Edema;443
62.1;Glossary;443
62.2;Diagnosis of Macular Edema;444
62.3;Anatomy of the Macula;444
62.4;Clinical Findings in Macular Edema;445
62.4.1;Clinically Significant Diabetic Macular Edema;445
62.4.2;Findings by Fluorescein Angiography;445
62.5;Causes of Macular Edema;449
62.6;Treatment of Macular Edema;449
62.6.1;Results from the ETDRS;449
62.6.2;Results of Other Clinical Trials;451
62.6.3;Anti-VEGF Therapies and Macular Edema;451
62.7;A Puzzling Question;452
62.8;Further Reading;454
63;Microvillar and Ciliary Photoreceptors in Molluskan Eyes;455
63.1;Glossary;455
63.2;Microvillar (Rhabdomeric) Photoreceptors;456
63.2.1;Excitation;456
63.2.2;Light Adaptation;458
63.2.3;Ciliary Photoreceptors;459
63.2.4;Excitation;459
63.2.5;Photopigment, G Protein, and Arrestin;460
63.2.6;Guanylate Cyclase;461
63.2.7;Light-Dependent Ion Channels;462
63.2.8;Light Adaptation;462
63.3;Further Reading;463
64;Morphology of Interneurons: Amacrine Cells;464
64.1;Glossary;464
64.2;AII Amacrine Cells;466
64.3;Starburst Amacrines;467
64.4;Further Reading;468
65;Morphology of Interneurons: Bipolar Cells;469
65.1;Glossary;469
65.2;Introduction;469
65.3;Bipolar Cell Types of the Mammalian Retina;469
65.3.1;Midget Bipolar Cells of the Primate Retina;470
65.3.2;Blue Cone Bipolar Cells;470
65.3.2.1;Clomeleon-labeled ganglion cells, amacrine cells and bipolar cells;471
65.3.3;Diffuse Bipolar Cells;472
65.3.4;Cone Bipolar Cells with Rod Input;472
65.4;Immunocytochemical Markers and Transgenic Mouse Lines;472
65.5;Synaptic Contacts of Bipolar Cells in the Inner Plexiform Layer;474
65.6;Costratification of Pre- and Postsynaptic Partners in the Inner Plexiform Layer;475
65.7;Bipolar Cells of Nonmammalian Vertebrates;476
65.7.1;Color-Coded Bipolar Cells in the Turtle Retina;477
65.8;Further Reading;477
66;Morphology of Interneurons: Horizontal Cells;478
66.1;Glossary;478
66.2;General Morphology and Connectivity;478
66.2.1;Basic Morphology;478
66.2.2;Photoreceptor Contacts;479
66.2.2.1;Contacts with cones;479
66.2.2.2;Contacts with rods;480
66.2.3;Population Properties and Gap-Junctional Coupling;481
66.3;Diversity of Morphology and Connectivity across Species;481
66.3.1;Variations of Shape;482
66.3.2;Species with Selective Cone Contacts;484
66.4;Conclusions and Open Questions;485
66.5;Further Reading;485
66.6;Relevant Website;486
67;Morphology of Interneurons: Interplexiform Cells;487
67.1;Glossary;487
67.2;Introduction;487
67.3;Morphology of Dopaminergic Interplexiform Neurons;487
67.3.1;Morphology and Distribution;488
67.3.1.1;Soma;488
67.3.1.2;Dendrites;488
67.3.1.3;Axon-like fine process;489
67.3.2;Synaptic Input to DA Neurons;489
67.3.2.1;Input from bipolar cells and amacrine cells;490
67.3.2.2;Input from intrinsically photoreceptive ganglion cells;490
67.3.2.3;Input from centrifugal fibers;490
67.4;Physiology of Dopaminergic Interplexiform Neurons;490
67.4.1;Dopamine Reconfigures Retinal Circuits;490
67.4.2;Light Drives Interplexiform Neurons via Both Conventional and Novel Pathways;491
67.4.3;IPCs Signal Time of Day from the Retinal Clock;492
67.5;DA Neurons and Retinal Degenerative Disease;492
67.5.1;Parkinson's Disease;492
67.5.2;Diabetic Retinopathy;492
67.5.3;Human Health Implications of the Retinal Clock;492
67.6;Summary;493
67.7;Further Reading;493
68;Neuropeptides: Function;494
68.1;Glossary;494
68.2;Introduction;494
68.3;Peptide Receptor Expression;494
68.3.1;Peptide-Binding Sites and Localization;495
68.3.2;Peptide Receptor messenger RNAs;495
68.4;Peptide Receptor Localization;495
68.4.1;Intracellular Signaling;495
68.5;Cellular Signaling;496
68.5.1;Ca2+ Imaging and Ion Channel Physiology;496
68.6;Functional Studies;499
68.6.1;Electroretinogram Recording;499
68.6.2;Extracellular Recordings;499
68.7;Peptide Influence on Transmitter Release;500
68.8;Peptide Function;501
68.9;Conclusion;502
68.10;Acknowledgments;502
68.11;Further Reading;502
69;Neuropeptides: Localization;504
69.1;Glossary;504
69.2;Introduction;504
69.3;Peptide Expression;504
69.3.1;Bioassays and Radioimmunoassays;504
69.4;Peptide Localization;505
69.4.1;Peptide Messenger RNA;505
69.4.2;Peptide Immunostaining;506
69.5;Peptide Receptor Expression;508
69.5.1;Peptide-Binding Sites and Localization;508
69.5.1.1;Peptide receptor mRNAs;508
69.5.2;Pharmacological Studies;508
69.6;Peptide Receptor Localization;508
69.6.1;Peptide Receptor mRNAs;508
69.6.2;Peptide Receptor Localization;508
69.7;Acknowledgments;510
69.8;Further Reading;510
70;Neurotransmitters and Receptors: Dopamine Receptors;511
70.1;Glossary;511
70.2;Localization of Dopamine Neurons in the Retina;511
70.3;Regulation of Dopamine Neuronal Activity;511
70.4;Dopamine Neuronal Activity Is Coupled to Dopamine Synthesis and Metabolism;511
70.5;Circadian Control of Dopamine Release and Metabolism;512
70.6;Dopamine Receptors;512
70.7;Functions of Dopamine in the Retina;513
70.7.1;Retinal Pigment Epithelium;513
70.7.2;Photoreceptor Cells;513
70.7.3;Horizontal Cells;513
70.7.4;Bipolar Cells;514
70.7.5;Amacrine Cells;514
70.7.6;Ganglion Cells;514
70.7.7;Muumlller Glial Cells;514
70.7.8;Role of Dopamine in Photopic Visual Processing;515
70.7.9;Dopamine and Circadian Organization of the Retina;515
70.7.10;Dopamine, Retinal Development, Ocular growth, and Myopia;515
70.8;Summary;515
70.9;Acknowledgments;515
70.10;Further Reading;516
71;Neurotransmitters and Receptors: Melatonin Receptors;517
71.1;Glossary;517
71.2;Introduction;517
71.3;Sites of Retinal Melatonin Synthesis;517
71.3.1;Melatonin Synthesis by Photoreceptors;517
71.3.2;Phylogenetic Relationships between Photoreceptors and Pinealocytes;518
71.4;Classification of Melatonin Receptors;518
71.5;Sites of Melatonin Receptors in the Retina;518
71.5.1;Melatonin Receptors in Photoreceptor Cells;518
71.5.2;Melatonin Receptors in RPE;519
71.5.3;Melatonin Receptors in Inner Retinal Neurons;519
71.6;Effects of Melatonin on Retinal Function;520
71.6.1;Modulation of Neurotransmitter Release;520
71.6.2;Modulation of Photoreceptor Function;520
71.7;Further Reading;521
72;Non-Invasive Testing Methods: Multifocal Electrophysiology;523
72.1;Glossary;523
72.2;Why Multifocal?;523
72.2.1;The Basic Principle;523
72.3;Recording of Multifocal Data;524
72.3.1;Multifocal Stimulators;525
72.3.2;Patient Positioning and Data Collection;525
72.3.3;Data Analysis and Presentation;525
72.3.4;Dealing with Noisy Data;525
72.3.5;How Long Does the Test Take?;525
72.4;Some Examples from the Retina Clinic;527
72.4.1;Central Serous Retinopathy;527
72.4.2;Hydroxychloroquine Retinopathy;527
72.4.3;Juvenile X-Linked Retinoschisis;527
72.4.4;Detecting Small Central Dysfunction;528
72.5;Applications to Neuro-Ophthalmology and Glaucoma;529
72.5.1;The mfVECP in Optic Neuritis;531
72.5.2;Comparison of the mfVEP and the mfERG in Optic Neuropathies and Glaucoma;531
72.5.3;Comparison of the mfVEP and the ONHC of the mfERG in an Asymmetric Glaucoma Patient;538
72.5.4;Patient with Unknown Vision Loss;540
72.6;Summary and Conclusion;540
72.7;Acknowledgments;541
72.8;Further Reading;541
73;Optical Coherence Tomography;542
73.1;Glossary;542
73.2;3D Ultrahigh Resolution Retinal OCT;543
73.3;3D Wide-Field Choroidal OCT;544
73.4;Cellular Resolution Retinal OCT;544
73.5;Functional Retinal Imaging Using OCT;548
73.6;Conclusion;551
73.7;Acknowledgments;551
73.8;Further Reading;551
74;Optic Nerve: Optic Neuritis;553
74.1;Glossary;553
74.2;Definition;553
74.3;Optic Nerve Anatomy;553
74.4;Immunopathogenesis;553
74.5;Epidemiology;554
74.6;Etiology;554
74.7;Symptoms;554
74.8;Diagnosis;554
74.8.1;Clinical Examination;554
74.8.2;Visual Evoked Potential;554
74.8.3;Magnetic Resonance Imaging;555
74.8.4;Cerebrospinal Fluid;555
74.8.5;Optical Coherence Tomography;556
74.9;Differential Diagnosis;556
74.10;Treatment;556
74.10.1;Neuroprotective Treatment Strategies;557
74.11;Prognosis;557
74.12;Further Reading;557
75;Pathological Retinal Angiogenesis;558
75.1;Glossary;558
75.2;Introduction;558
75.3;Promoters and Inhibitors of Angiogenesis;558
75.3.1;Promoters of Angiogenesis;559
75.3.1.1;Vascular endothelial growth factor;559
75.3.1.2;Placental growth factor;561
75.3.1.3;Platelet-derived growth factor;561
75.3.1.4;Notch;562
75.3.1.5;Tumor necrosis factor-alpha;563
75.3.1.6;Ephrins and Ephs;563
75.3.1.7;Angiopoietins;564
75.3.1.8;Erythropoietin;565
75.3.1.9;Integrins;565
75.3.1.10;Matrix metalloproteinases;565
75.3.1.11;Components of the complement cascade;565
75.3.2;Inhibitors of Angiogenesis;566
75.3.2.1;Pigment epithelium-derived factor;566
75.3.2.2;VEGFxxxb isoforms;566
75.3.2.3;Soluble VEGF receptor 1;566
75.3.2.4;Complementary regulatory protein CD59;566
75.3.2.5;Tryptophanyl-tRNA synthase fragment;566
75.3.2.6;Slit/Roundabout4;566
75.3.2.7;Other inhibitors;566
75.4;New Directions in Antiangiogenic Therapy;566
75.5;Conclusions;567
75.6;Further Reading;567
76;Perimetry;568
76.1;Glossary;568
76.2;Perimetric Techniques;568
76.2.1;Kinetic Perimetry;568
76.2.2;Static Threshold Perimetry;568
76.2.3;Static Suprathreshold Perimetry;569
76.3;Test Targets;569
76.3.1;Standard Achromatic Perimetry;570
76.3.2;Short-Wavelength Automated Perimetry;570
76.3.3;High-Pass Resolution Perimetry (Ring Perimetry);570
76.3.4;Frequency-Doubling Technology Perimeter;571
76.4;Reliability Estimates;571
76.4.1;Fixation Accuracy;571
76.4.2;False-Positive Responses;572
76.4.3;False-Negative Responses;572
76.5;Analytical Techniques;572
76.5.1;Total Deviation and Pattern Deviation Plots;572
76.5.2;Global Indices;572
76.5.3;Linear Regression;573
76.5.4;Change Probability;573
76.6;Further Reading;573
76.7;Relevant Websites;574
77;Photopic, Mesopic and Scotopic Vision and Changes in Visual Performance;575
77.1;Glossary;575
77.2;Introduction;575
77.3;The Concept of Luminous Efficiency Function;577
77.4;Quality of Vision and Light Level;578
77.4.1;Spatial Acuity, Spatial Contrast Sensitivity, and Light Level;578
77.4.2;Pupil Size, Higher order Aberrations, and Light Level;579
77.4.3;Flicker Perception;580
77.4.4;Color Vision and Light Level;582
77.5;Conclusions;582
77.6;Further Reading;583
78;Photoreceptor Development: Early Steps/Fate;584
78.1;Glossary;584
78.2;Introduction;584
78.3;Photoreceptor Development;585
78.3.1;Rod and Cone Pattern in Human and Mouse Retina;585
78.3.2;Development of Cone and Rod Photoreceptors;585
78.4;Factors Affecting Photoreceptor Genesis;586
78.5;Early Stages in Photoreceptor Development;586
78.5.1;From RPC to Photoreceptor Precursor;586
78.6;From Cone Precursor to Cone Photoreceptor;588
78.7;From Rod Precursor to Rod Photoreceptor;589
78.8;Maturation of Photoreceptors;590
78.9;Current Research in Photoreceptor Development;590
78.10;Conclusions;591
78.11;Further Reading;591
79;The Photoreceptor Outer Segment as a Sensory Cilium;592
79.1;Glossary;592
79.2;Introduction;592
79.3;Turnover of the OS and Phototransduction Machinery;592
79.4;The Photosensitive Organelle as a Sensory Cilium;593
79.5;Evidence for Intraflagellar Transport in Photoreceptors;595
79.6;A Special Role for KIF17 in Photoreceptors;596
79.7;What Is the IFT Cargo?;597
79.8;Summary and Perspective;598
80;The Photoresponse in Squid;599
80.1;Glossary;599
80.2;Introduction;599
80.3;Molecular Components of Squid Visual Signal Transduction;599
80.4;Squid Rhodopsin;599
80.5;Squid Visual Guanine Nucleotide-Binding Protein, Gq;602
80.6;Squid Visual PLC;603
80.7;Light-Activated Ion Channel;603
80.8;Desensitization of Visual Signal Transduction;603
80.9;Squid Rhodopsin Kinase;603
80.10;Squid Visual Arrestin;604
80.11;Conclusion;605
80.12;Further Reading;605
81;Phototransduction: Adaptation in Cones;606
81.1;Glossary;606
81.2;Performance of the Photopic (Cone) System;606
81.2.1;Workhorse of Vision;606
81.2.2;Rapid Response and Moderate Sensitivity;606
81.2.3;Avoidance of Saturation;606
81.3;Light Adaptation of the Cones;607
81.3.1;Flashes on Backgrounds: Desensitization and Acceleration;607
81.3.2;Dependence of Sensitivity on Background Intensity: Weber's Law;608
81.3.3;Extremely Rapid Recovery of Cone Photocurrent;609
81.4;Molecular Basis of Cone Light Adaptation;610
81.4.1;Reaction Steps Underlying Rapid Recovery of the Cone's Light Response;610
81.4.2;Cone Avoidance of Saturation;611
81.4.3;Modeling of Human Cone Light Adaptation;611
81.5;Further Reading;612
82;Phototransduction: Adaptation in Rods;613
82.1;Glossary;613
82.2;Vision over a Billion-Fold Range of Light Intensities;613
82.3;Performance of the Scotopic (Rod) System;613
82.4;The Purpose of Light Adaptation: Optimization of Performance;615
82.4.1;Avoidance of Saturation: Range Extension;615
82.4.2;Extraction of Contrast Information and Optimization of Response Kinetics;615
82.5;Light Adaptation of the Rod Photoreceptors: Range Extension, Desensitization, and Acceleration;615
82.5.1;Prevention of Rod Photoreceptor Saturation: Range Extension;615
82.5.2;Desensitization and Acceleration;616
82.5.3;Unaltered Rising Phase, but Accelerated Recovery;616
82.6;Saturation of the Rod Photocurrent at Higher Background Intensities;617
82.7;Calcium-Dependent Mechanisms of Rapid Light Adaptation in Rod Photoreceptors;617
82.7.1;Role of Calcium: Resensitization through Prevention of Saturation;617
82.7.2;Powerful Negative-Feedback Loop Mediated by Calcium;617
82.7.3;Three Calcium-Sensitive Molecular Pathways;618
82.7.3.1;Guanylyl cyclase activation;618
82.7.3.2;Shortened Rast lifetime;618
82.7.3.3;Channel reactivation;619
82.8;Rod Photoreceptor Light Adaptation Independent of Calcium;619
82.8.1;Accelerated Turnover of cGMP;619
82.9;Slow Changes in Rods: Light Adaptation or Dark Adaptation?;619
82.9.1;Light-Induced Change in the Dominant Time Constant;619
82.9.2;Light-Induced Translocation of Proteins;620
82.10;Dark Adaptation of the Rods: Very Slow Recovery from Bleaching;620
82.11;Further Reading;621
83;Phototransduction: Inactivation in Cones;622
83.1;Glossary;622
83.2;Cone Signaling Cascade;622
83.3;Shutoff of the Light-Activated Cone Opsins;623
83.4;Inactivation of Transducin and PDE;624
83.5;Restoration of cGMP and Intracellular Calcium Level;624
83.6;Conclusions;624
83.7;Further Reading;626
84;Phototransduction: Inactivation in Rods;627
84.1;Glossary;627
84.2;What Needs to Be Inactivated: Overview of the Signaling Cascade;627
84.3;Shutoff of the Light-Activated Rhodopsin;628
84.4;Inactivation of Td and PDE;629
84.5;Resynthesis of cGMP and Restoration of Calcium Level;629
84.6;Light-Dependent Protein Translocation and Rod Signaling;631
84.7;Why Rods Do Not Have an Action Potential;632
84.8;Conclusions;632
84.9;Further Reading;632
85;Phototransduction in Limulus Photoreceptors;633
85.1;Glossary;633
85.2;Arrangement of Eyes in Limulus;633
85.3;The Microvillus is the Cellular Structure Mediating Visual Transduction;633
85.4;Studies of Visual Transduction Using Limulus Ventral Photoreceptors;634
85.5;The Light-Sensitive Conductance Consists of the Summed Effect of Conventional Ion Channels;635
85.6;The Response of the Ventral Photoreceptor is Mediated by the Phosphoinositide Cascade;636
85.7;The PI Cascade Generates at Least Two Intracellular Messenger Molecules;636
85.8;Roles of IP3 and Intracellular Ca2+ Ions in Excitation of Limulus Ventral Photoreceptors;637
85.9;IP3 Can Release Ca2+ from the SER;637
85.10;Released Ca2+ Ions can Activate an Inward Current;638
85.11;Light-Induced Ca2+ Release can be Detected before the Electrical Response;638
85.12;How Does IP3-Induced Ca2+ Release Activate Inward Current and is this Current Flowing through the Light- Sensitive Conductance?;639
85.13;Adaptation, a Decrease in the Sensitivity of the Visual Cascade, is Mediated by Small, Lingering Elevations of Ca2+;639
85.14;Drosophila and Limulus Photoreceptors Operate Differently and Illustrate Two General Mechanisms Coupling the PI Cascade to an E;640
85.15;Extension of Phototransduction Mechanisms to other Microvillar Photoreceptor Types;640
85.16;Further Reading;640
86;Phototransduction: Phototransduction in Cones;641
86.1;Glossary;641
86.2;Introduction;641
86.3;Functional Properties of Cones;641
86.4;Obstacles for Studying Cone Phototransduction;642
86.5;Cone Visual Pigment and Phototransduction;643
86.6;Activation of Cone Phototransduction;644
86.7;Inactivation of Cone Phototransduction;644
86.8;Dark Adaptation of Cones;645
86.9;Light Adaptation in Cones;646
86.10;Epilog;647
86.11;Further Reading;647
87;Phototransduction: Phototransduction in Rods;648
87.1;Glossary;648
87.2;Introduction;648
87.3;Vertebrate Rods Are Highly Efficient Photon Detectors;648
87.4;Phototransduction in Rods: A G-Protein-Signaling Pathway;648
87.5;High Quantum Efficiency of Photoactivation;649
87.6;The Great Thermal Stability of Rhodopsin;649
87.7;The Activation of Transducin Constitutes the First Amplification Step;650
87.8;The High Catalytic Power of PDE Accounts For the Second Amplification Step;651
87.9;cGMP Is the Second Messenger Mediating Rod Phototransduction;652
87.10;The cGMP-Gated Channel Provides the Final Step of Signal Amplification;652
87.11;Further Reading;653
88;Phototransduction: Rhodopsin;654
88.1;Glossary;654
88.2;Rod Cells and Rhodopsin;654
88.3;Structure of Rhodopsin;655
88.4;Chromophore-Binding Site;658
88.5;Rhodopsin Cycle - Retinal Isomerization;658
88.6;Visual Cycle - Rhodopsin Regeneration;659
88.7;Vertebrate versus Invertebrate Rhodopsins;660
88.8;Signaling Cycle;661
88.9;Rhodopsin Interaction with Other Proteins;661
88.9.1;Rhodopsin-G t;662
88.9.2;Rhodopsin-GRK 1;662
88.9.3;Rhodopsin-Arrestin ;662
88.10;Mutations in Rhodopsin and Retinal Diseases;662
88.11;Further Reading;663
89;Phototransduction: The Visual Cycle;665
89.1;Glossary;665
89.2;Clearance of All-trans-RAL from OS Disks;665
89.3;Reduction of All-trans-RAL to All- trans- ROL;666
89.4;Transfer of All-trans-ROL from Photoreceptors to the RPE;666
89.5;Synthesis of Retinyl Esters;667
89.6;Retinoid Isomerization;667
89.7;Synthesis of 11-cis-RAL Chromophore;668
89.8;Regeneration of Rhodopsin or Cone Opsin;668
89.9;Regulation of the Visual Cycle;668
89.10;Further Reading;668
90;Physiological Anatomy of the Retinal Vasculature;670
90.1;Glossary;670
90.2;Arterial Supply of the Retina;670
90.2.1;Central Retinal Artery;670
90.2.2;Cilioretinal Artery;670
90.2.3;Intraretinal Branches of the CRA;671
90.2.4;Retinal Capillary Bed;672
90.3;Retinal Venous Drainage;674
90.4;Nerve Supply;675
90.5;Blood-Retinal Barrier;676
90.6;Autoregulation of Retinal Blood Flow;676
90.7;Further Reading;677
91;The Physiology of Photoreceptor Synapses and Other Ribbon Synapses;678
91.1;Glossary;678
91.2;Anatomy of the Ribbon Synapse;678
91.3;Vesicle Pools and Vesicular Release at Synaptic Ribbons;679
91.4;Role of the Ribbon in Release;680
91.5;Synaptic Proteins;680
91.6;Photoreceptor Calcium Channels;681
91.7;Role of Intracellular Ca2+ in Release;682
91.8;Physiology of Release at Photoreceptor Synapses;682
91.9;Disease-Related Mutations in Synaptic Proteins at the Photoreceptor Synapse;683
91.10;Further Reading;684
92;Polarized-Light Vision in Land and Aquatic Animals;685
92.1;Glossary;685
92.2;Polarized Light in Nature;686
92.3;Polarization Sensitivity and Polarization Vision;687
92.3.1;Polarization Responses of Photoreceptor Cells;687
92.3.1.1;Polarization sensitivity;688
92.3.1.2;Polarization vision;689
92.3.1.3;Disentangling polarization and color sensitivity;689
92.4;The Contributions of Polarized-Light Perception to Behavior;690
92.5;Sensitivity to Circularly Polarized Light;691
92.6;Summary;691
92.7;Further Reading;692
93;Post-Golgi Trafficking and Ciliary Targeting of Rhodopsin;693
93.1;Glossary;693
93.2;Introduction;693
93.3;Photoreceptor Polarity;693
93.4;Photoreceptor Biosynthetic Membrane Trafficking: Endoplasmic Reticulum, Golgi, and Post-Golgi Transport Carriers;694
93.5;Small GTPases of the Rab and Arf Families and Their Regulators in Rhodopsin Trafficking;695
93.5.1;Rabs;695
93.5.2;Arfs;696
93.5.3;SNAREs and their Regulators in Rhodopsin Trafficking;696
93.6;ROS is a Modified Primary Cilium;697
93.7;Conclusions anSummary;699
93.8;Further Reading;700
93.9;Relevant Websites;700
94;Primary Photoreceptor Degenerations: Retinitis Pigmentosa;701
94.1;Glossary;701
94.2;Background;702
94.3;Prevalence;703
94.4;Inheritance;703
94.4.1;Autosomal Recessive;703
94.4.2;X-Linked RP;703
94.4.3;Autosomal Dominant;703
94.5;Nonsyndromic versus Syndromic Retinal Degeneration;703
94.6;Classification of RP;704
94.6.1;Classification by Age of Onset;704
94.6.2;Classification by Fundus Appearance;706
94.6.3;Classification by Functional Loss;707
94.7;Mechanism of Disease;707
94.8;Clinical Presentation;707
94.8.1;Symptoms;707
94.8.2;Refraction;707
94.8.3;Anterior Segment and Cataract;707
94.8.4;Fundus Findings;707
94.9;Diagnostic Tests for RP;708
94.9.1;Dark Adaptation;708
94.9.2;Visual Fields;708
94.9.3;Electroretinograms;708
94.9.4;Fundus Photography/Fluorescein Angiography;709
94.9.5;Optical Coherence Tomography;709
94.10;Differential Diagnosis;709
94.11;Prognosis in RP;711
94.12;Current Treatments;711
94.12.1;Treatable Forms of RP;711
94.12.2;Resources/Support for Patients with RP;711
94.12.3;Optimizing Remaining Vision;712
94.12.4;Vitamin A;713
94.12.5;Docosahexanoic Acid;713
94.12.6;Neuroprotection/CNTF;713
94.12.7;Gene Therapy;713
94.12.8;Autologous RPE Transplantation;714
94.12.9;Stem-Cell-Based Therapies;714
94.12.10;Microelectrode Implants;714
94.12.11;Expression of Photosensitive Proteins;714
94.13;Conclusions;714
94.14;Further Reading;714
94.15;Relevant Websites;714
95;Primary Photoreceptor Degenerations: Terminology;715
95.1;Glossary;715
95.2;Histological and Fundus Features of Retinitis Pigmentosa;716
95.2.1;Bone Spicule Pigmentation;716
95.2.2;Waxy Pallor of the Optic Nerve;716
95.2.3;Peripapillary/Optic Nerve Head Drusen;716
95.2.4;Bull's Eye Maculopathy;716
95.2.5;Coats-Like Response;717
95.3;Classification of RP by Fundus Pattern;717
95.3.1;Classic Pattern for RP;717
95.3.2;Inverse RP;717
95.3.3;Concentric RP;718
95.3.4;Sector RP;718
95.3.5;RP Sine Pigmento;718
95.3.6;Tapetal-Like Reflex/Sheen;718
95.3.7;RP with Preserved Peri-Arteriolar RPE;718
95.3.8;Pigmented Paravenous Retinochoroidal Atrophy;719
95.3.9;Fundus Albipunctata;719
95.3.10;Retinitis Punctata Albescens;719
95.3.11;Gyrate Atrophy;719
95.3.12;Choroideremia;720
95.4;Syndromic Forms of RP;720
95.4.1;Abetalipoproteinemia;720
95.4.2;Alstroumlm Syndrome;721
95.4.3;Bardet-Biedl Syndrome;721
95.4.4;Chronic Progressive External Ophthalmoplegia/Kearns-Sayre Syndrome;721
95.4.5;Friedreich's Ataxia;721
95.4.6;Vitamin E Deficiency;721
95.4.7;Incontinentia Pigmenti (Bloch-Schulzberg Syndrome);721
95.4.8;Joubert Syndrome;721
95.4.9;Mucopolysaccharide Disorders;721
95.4.10;Neuronal Ceroid Lipofuscinosis (Batten Disease);721
95.4.11;Infantile Refsum Disease;722
95.4.12;Adult Refsum Disease;722
95.4.13;Senior-Loken Syndrome;722
95.4.14;Spinocerebellar Ataxia Type 7;722
95.4.15;Usher Syndrome;722
95.5;Visual Testing in RP;722
95.5.1;Terminology of Light Adaptation;722
95.5.2;Dark Adaptation;722
95.5.3;Visual Fields;722
95.6;ERG Terminology;722
95.6.1;Full-Field ERG;722
95.6.2;Multifocal ERG;723
95.6.3;Rod-Isolated ERG Response;723
95.6.4;Mixed Rod-Cone ERG Response;723
95.6.5;Cone-Isolated ERG Response;723
95.7;Further Reading;723
95.8;Relevant Websites;724
96;Proliferative Vitreoretinopathy;725
96.1;Glossary;725
96.2;Introduction;725
96.3;Definition;725
96.4;Location of PVR Membranes;725
96.5;The Significance of Membrane Formation in PVR;725
96.6;The Cells Involved in PVR;726
96.6.1;Glial Cells;727
96.6.2;RPE Cells;728
96.6.3;Fibroblastic Cells;728
96.6.4;Macrophages;728
96.6.5;Vascular Elements;728
96.6.6;Other Cells;728
96.7;The Extracellular Matrix in PVR Membranes;728
96.8;Pathogenesis and Natural History;729
96.8.1;Intraretinal PVR;730
96.9;Incidence and Risk Factors;730
96.10;Clinical Classification of Proliferative Vitreoretinopathy;731
96.11;Management;731
96.12;Outcomes;732
96.13;Conclusions;732
96.14;Further Reading;732
96.15;Relevant Website;733
97;Retinal Cannabinoids;734
97.1;Glossary;734
97.2;Marijuana and the Endocannabinoids;734
97.2.1;Synthesis and Release;734
97.2.2;Inactivation;734
97.2.3;Receptors;734
97.2.4;Distribution and Function;735
97.3;Cannabinoids and Ocular Tissues;736
97.4;Cannabinoids - Retinal Anatomy;736
97.4.1;Biochemical Assay;736
97.4.2;Localization - Cannabinoid Receptors;736
97.4.3;Localization - Metabolizing Enzymes;737
97.5;Cannabinoids - Retinal Physiology;737
97.5.1;Effects on Transmitter Release;737
97.5.2;Effects on Ganglion cells;738
97.5.3;Effects on Bipolar Cells;738
97.6;Cannabinoids and Photoreceptors;738
97.6.1;Voltage-Gated Currents;738
97.6.2;WIN 55,212-2 Affects the Cone Light Response;741
97.7;Cannabinoids - Development and Neuroprotection;741
97.8;Conclusion;741
97.9;Further Reading;742
97.10;Relevant Websites;742
98;Retinal Degeneration through the Eye of the Fly;743
98.1;Glossary;743
98.2;The Compound Eye and Phototransduction;746
98.3;Genetic Screens Identify Retinal Degeneration Loci;747
98.4;Retinal Degenerations in Flies and Humans;747
98.5;Mechanisms of Retinal Degenerations;748
98.5.1;Light-Dependent Retinal Degenerations;748
98.5.2;Light-Independent Retinal Degenerations;748
98.5.3;Retinal Degenerations Caused by Mutations in Dual-Role Proteins;749
98.5.4;Summary;749
98.6;Acknowledgments;749
98.7;Further Reading;750
98.8;Relevant Website;750
99;Retinal Ganglion Cell Apoptosis and Neuroprotection;751
99.1;Glossary;751
99.2;Introduction;751
99.3;Apoptosis;751
99.3.1;Apoptosis in Glaucoma;751
99.4;Diagnosis and Measuring Glaucoma Progression;751
99.5;Current Treatments for Glaucoma;752
99.6;Neuroprotection;753
99.7;Research Models;753
99.7.1;In Vitro Glaucoma Models;753
99.7.2;In Vivo Glaucoma Models;753
99.8;Mechanisms of Apoptosis and Development of Neuroprotective Agents;753
99.8.1;Neurotrophic Factor Withdrawal;753
99.8.2;NFs as Neuroprotective Agents;753
99.8.3;Excitotoxicity;754
99.8.4;NMDA-Antagonists and Neuroprotective Agents;755
99.8.5;Reactive Oxygen Species;756
99.8.6;Mitochondrial Dysfunction and ROS Generation;756
99.8.7;Antioxidants as Neuroprotective Agents;757
99.8.8;Protein Misfolding;757
99.8.9;Reduction of Misfolded Proteins in Neuroprotection;758
99.8.10;Glial-Neuronal Interactions;758
99.8.11;Extracellular Matrix Degradation;759
99.8.12;Neuroprotective Vaccine;760
99.9;Summary;760
99.10;Further Reading;760
100;Retinal Histogenesis;762
100.1;Glossary;762
100.2;Birthdating;762
100.3;Lineage Tracing;763
100.4;Environmental Challenge;765
100.5;Transcription Factors and Competence;767
100.6;Conclusions;768
100.7;Further Reading;769
101;Retinal Pigment Epithelial-Choroid Interactions;770
101.1;Glossary;770
101.2;Introduction;770
101.3;RPE-C horoid Complex Development;770
101.3.1;RPE Development;770
101.3.2;Choroid Development;771
101.3.3;BrM Development;772
101.4;RPE-C horoid Complex: Structure and Function;772
101.4.1;RPE Structure and Function;772
101.4.2;Choroid Structure and Function;772
101.4.3;BrM Structure and Function;773
101.5;RPE-C horoid Interactions;773
101.5.1;Interactions During Development;773
101.5.2;Interactions in the Adult;774
101.5.2.1;Growth factor secretion;774
101.5.2.2;Receptor expression;774
101.5.2.3;Isoform-specific VEGF mouse model;774
101.5.2.4;Choroidal change impact on RPE;774
101.6;RPE-C horoid Changes with Age;775
101.6.1;BrM Changes;775
101.6.2;Gene Expression;775
101.7;Conclusions;776
101.8;Further Reading;777
102;Retinal Pigment Epithelium: Cytokine Modulation of Epithelial Physiology;778
102.1;Glossary;778
102.2;Introduction;778
102.3;Human RPE: Morphology, Polarity, and Function;779
102.3.1;pHi - Induced Changes in Fluid Absorption;779
102.4;Modulation of SRS Metabolic Load and Chemical Composition;780
102.5;Oxidative Stress;783
102.6;RPE-I mmune System Interactions in and around the SRS;784
102.7;Modulation of RPE Proliferation and Migration by Cytokines and Growth Factors;784
102.8;IFNgamma Regulation of RPE Fluid Transport;787
102.9;Leukocyte Migration across the RPE: A Model of Disease Progression;788
102.10;Further Reading;789
103;RPE Barrier;790
103.1;Glossary;790
103.2;Introduction;790
103.3;Structure and Function;791
103.3.1;Tissue Level;791
103.3.2;Cellular Level;792
103.3.3;Molecular Level;792
103.4;Regulation of RPE Tight Junctions;794
103.4.1;Clues from Embryonic Maturation;794
103.4.2;Assembly of Tight Junctions during Differentiation;794
103.5;Culture Models to Study Regulation of the Outer Blood-Retinal Barrier;795
103.6;RPE in the Larger Context of Ocular Biology and Disease;796
103.7;Further Reading;796
104;Retinal Vasculopathies: Diabetic Retinopathy;798
104.1;Glossary;798
104.2;Background;798
104.3;Risk Factors for DR;799
104.4;Pathogenesis;799
104.5;Classifications;801
104.6;Nonproliferative Diabetic Retinopathy;801
104.7;Macular Edema;802
104.8;Proliferative Diabetic Retinopathy;803
104.9;Screening for Diabetic Retinopathy;805
104.10;Further Reading;805
105;Retinopathy of Prematurity;807
105.1;Glossary;807
105.2;Clinical Background;807
105.2.1;Epidemiology;807
105.2.2;Clinical Classification of ROP;807
105.2.3;Management of ROP;808
105.2.4;Treatment of ROP;809
105.2.4.1;Acute neovascular stages;809
105.2.4.2;Fibrovascular stages/retinal detachment;809
105.2.4.3;Visual rehabilitation in preterm infants;812
105.3;Genetics Related to ROP;812
105.4;Pathophysiology of ROP;812
105.4.1;Role of Oxygen in Retinal Development;812
105.4.2;Animal Models of Severe ROP;813
105.4.2.1;Mouse OIR (model of aggressive posterior ROP);813
105.4.2.2;Rat 50/10 OIR (model of peripheral severe ROP);813
105.4.3;Role of Avascular Retina;813
105.4.4;Role of Growth Factors;815
105.4.4.1;Vascular Endothelial Growth Factor;815
105.4.4.2;IGF-1 - IGF 1BP3;815
105.4.4.3;Erythropoietin;815
105.4.4.4;HIF 1alpha;815
105.4.5;Role of Oxidative Stress;815
105.5;Future Treatment Considerations;816
105.6;Further Reading;816
106;Rhegmatogenous Retinal Detachment;818
106.1;Glossary;818
106.2;Pathophysiology;818
106.3;Clinical Features;818
106.3.1;Symptoms;818
106.3.2;Signs;819
106.3.2.1;Break type - identification;819
106.3.2.1.1;Retinal tears;819
106.3.2.1.2;Retinal round holes;819
106.3.2.1.3;Retinal dialyses;820
106.3.2.2;Break localization - principles based on topography of RRD;820
106.3.2.2.1;Superotemporal and superonasal;820
106.3.2.2.2;Midline (12 o'clock meridian) and total detachments;820
106.3.2.2.3;Inferior;820
106.3.2.3;Chronic RRD;820
106.4;Differential Diagnoses;820
106.5;Management;821
106.5.1;Conservative;821
106.5.1.1;RRD due to retinal tear;821
106.5.1.2;RRD due to retinal hole or dialysis;821
106.5.2;Laser Demarcation;821
106.5.2.1;RRD due to retinal tear;822
106.5.2.2;RRD due to retinal hole or dialysis;822
106.5.3;Pneumatic Retinopexy;822
106.5.3.1;RRD due to retinal tear;823
106.5.3.2;RRD due to retinal hole or dialysis;823
106.5.4;Scleral Buckling;823
106.5.4.1;RRD due to retinal tear;823
106.5.4.2;RRD due to retinal hole or dialysis;823
106.5.5;Vitrectomy;823
106.5.5.1;RRD due to retinal tear;823
106.5.5.2;RRD due to retinal hole or dialysis;824
106.6;Outcomes;824
106.6.1;Pneumatic Retinopexy;824
106.6.2;Scleral Buckling;825
106.6.3;Pars Plana Vitrectomy;825
106.7;Complications;825
106.7.1;Pneumatic Retinopexy;826
106.7.2;Scleral Buckling;826
106.7.3;Pars Plana Vitrectomy;826
106.7.4;Treatment Failure;826
106.8;New Developments;826
106.9;Further Reading;826
107;Rod and Cone Photoreceptor Cells: Inner and Outer Segments;828
107.1;Glossary;828
107.2;Further Reading;831
108;Rod and Cone Photoreceptor Cells: Outer Segment Membrane Renewal;832
108.1;Glossary;832
108.2;Further Reading;835
109;Rod Photoreceptor Cells: Soma and Synapse;836
109.1;Glossary;836
109.2;Introduction;836
109.3;Structure;836
109.3.1;Morphology and Topology;836
109.3.2;Axon and Terminal;836
109.3.3;Synapse;837
109.3.4;Invagination;838
109.3.5;Biophysical Properties;838
109.3.6;Gap Junctions;838
109.4;Function;838
109.4.1;The Single-Photon Signal and Noise;838
109.4.2;Sources of Noise;838
109.4.3;Synaptic Transfer Function: High Gain and Temporal Filtering;839
109.4.4;Rate of Vesicle Release;839
109.4.5;Synaptic Transfer Function: Nonlinear Threshold;839
109.4.6;Electrical Coupling in Starlight;840
109.4.7;Electrical Coupling in Twilight;840
109.4.8;Negative Feedback;840
109.5;Conclusion;841
109.6;Acknowledgments;841
109.7;Further Reading;841
110;The Role of the Vitreous in Macular Hole Formation;842
110.1;Glossary;842
110.2;Vitreous Anatomy and Biochemistry;842
110.3;Vitreous Traction;842
110.4;Vitreoretinal Interface;843
110.5;Confounding Observations;844
110.6;Summary;845
110.7;Further Reading;845
111;Secondary Photoreceptor Degenerations: Age-Related Macular Degeneration;847
111.1;Glossary;847
111.2;Introduction;847
111.3;Incidence;847
111.4;The Macula;847
111.5;Clinical Symptoms;848
111.6;Histopathology;849
111.7;Risk Factors;849
111.8;Genetics;850
111.8.1;CFH;850
111.8.2;ARMS2/HTRA1;851
111.9;Treatments;851
111.10;Further Reading;851
111.11;Relevant Websites;852
112;Secondary Photoreceptor Degenerations;853
112.1;Glossary;853
112.2;Introduction;853
112.3;Mechanisms of Secondary Photoreceptor Death;856
112.4;Further Reading;857
112.5;Relevant Website;857
113;Unique Specializations - Functional: Dynamic Range of Vision Systems;858
113.1;Glossary;858
113.2;Introduction;858
113.3;Rods versus Cones;858
113.4;The Pathways Concept;858
113.4.1;Rod Bipolar Pathway;859
113.4.1.1;Signal transfer from rods to rod bipolar cells;859
113.4.1.2;Signal transfer from rod bipolar cells to AII amacrine cells;860
113.4.1.3;Ganglion cell sensitivity;860
113.4.2;Rod-Cone Pathway;861
113.4.3;Rod-OFF Pathway;861
113.4.4;Cone Pathways;862
113.5;Adaptation to Mean Background Light;862
113.5.1;Adaptation: Rod Pathways;862
113.5.2;Adaptation: Cone Pathways;862
113.6;Conclusions;863
113.7;Further Reading;863
114;Xenopus laevis as a Model for Understanding Retinal Diseases;864
114.1;Glossary;864
114.2;Introduction;864
114.3;Early Work on X. laevis - Biochemistry, Electrophysiology, and Microscopy;864
114.4;X. laevis as a Model for Vitamin A Deprivation;865
114.5;X. laevis as a Model for Glaucoma;865
114.6;X. laevis and Studies of the Transport of Rhodopsin;866
114.7;Modeling RP in Transgenic X. laevis;866
114.8;Inducible RD;868
114.9;Other Transgenic X. laevis Models of Retinal Disease;868
114.10;X. laevis as a Model for Eye Development/Developmental Disorders;868
114.11;X. laevis Models of Retinal Regeneration;868
114.12;Summary;869
114.13;Further Reading;869
115;Zebra Fish as a Model for Understanding Retinal Diseases;870
115.1;Glossary;870
115.2;Introduction;870
115.3;Retinal Disease;871
115.4;Animal Models of Vision;871
115.4.1;The Advantages and Techniques of the Zebrafish Model System;871
115.4.1.1;Evaluating zebrafish vision;873
115.5;The Visual System: Phosphodiesterase and Phototransduction;873
115.6;Retinal Degeneration in pde6 Mutants: Primary Degeneration;874
115.7;Retinal Degeneration in pde6 Mutants: Secondary Retinal Degeneration, the Bystander Effect - Models and Mechanisms;874
115.7.1;Levels of the Bystander Effect in Photoreceptor Degeneration;875
115.8;Zebrafish Models of Retinal Degeneration: Mutations in pde6c;875
115.8.1;pde6cw59;875
115.8.2;els;877
115.8.3;Pde6 Structure;877
115.9;Conclusion;879
115.10;Further Reading;879
116;Zebra Fish-Retinal Development and Regeneration;880
116.1;Glossary;880
116.2;Introduction;880
116.3;Embryonic Eye Patterning;881
116.3.1;Zebrafish Eyes Form from a Single Field in the Anterior Neural Plate;881
116.3.2;The Laminar Structure of the Retina Forms as Cells Exit the Cell Cycle and Differentiate;881
116.3.3;Addition of Retinal Cells Throughout the Life of a Zebrafish;882
116.3.4;Regeneration in the Zebrafish Retina;882
116.3.4.1;Zebrafish regenerate all retinal neurons;882
116.3.5;Constant Intense Light Kills Photoreceptors, Which Are then Regenerated by Müller Glia;884
116.3.6;Discovery and Analysis of Candidate Genes Involved in Retinal Regeneration;886
116.3.7;Events Underlying Regeneration of the Light- Damaged Retina;888
116.3.8;Vestigial Retinal Regeneration Activity in Mammals;889
116.3.9;Similarities and Differences of Development with Retinal Ontogeny/Genesis;889
116.4;Further Reading;889
117;Subject Index;892