The Retina and Circadian Rhythms (Springer Series in Vision Research Book 1)

Daily rhythms are a ubiquitous feature of living systems. Generally, these rhythms are not just passive consequences of cyclic fluctuations in the environment, but instead originate within the organism. In mammals, including humans, the master pacemaker controlling 24-hour rhythms is localized in the suprachiasmatic nuclei of the hypothalamus (SCN). This circadian clock is responsible for the temporal organization of a wide variety of functions, ranging from sleep and food intake, to physiological measures such as body temperature, heart rate and hormone release. Moreover, accumulating evidence suggests that dysfunction of the circadian rhythms due to genetic mutations or environmental factors (i.e., jet-lag or shift work) contribute to the development of many pathologies, including sleep disorders, mood and affective disorders such as major depression, bipolar disorder and schizophrenia, as well as the risk of metabolic and cardiovascular disorders. Contents 6 Contributors 8 Chapter 1: Introduction 10 Chapter 2: Fundamental Retinal Circuitry for Circadian Rhythms 12 2.1 Introduction 13 2.2 Classes and Types of Retinal Neurons 13 2.3 Photoreceptors: Cones and Rods 15 2.4 Outer Segment Renewal 19 2.5 Horizontal Cells 19 2.6 Bipolar Cells and ON and OFF Channels 21 2.7 The Rod Pathway and the Piggyback Arrangement 23 2.8 AII Amacrine Cells 25 2.9 The Rod Pathway and Dopaminergic Amacrine Cells: The Power of Being Few 26 2.10 Possible Explanation and Advantages of the Piggyback Arrangement 27 2.11 Diverse and Complex Retinal Neurons: Amacrine and Ganglion Cells 28 2.12 Ganglion Cells 29 2.13 Melanopsin Ganglion Cells 31 2.14 Conclusions 33 References 33 Chapter 3: Circadian Photoreception: From Phototransduction to Behaviour 36 3.1 Introduction 37 3.2 Retinal Photoreceptors 38 3.3 Light Transduction to the SCN 42 3.4 Light-Response Characteristics in the SCN 44 3.5 Phase Response Curve 46 3.6 Contribution of Photoreceptors to Photoentrainment 48 3.7 Conclusions 51 References 51 Chapter 4: Role of Melatonin and Dopamine in the Regulation of Retinal Circadian Rhythms 58 4.1 Melatonin Synthesis and Metabolism 59 4.2 Melatonin: Site of Action and Signaling 62 4.3 Dopamine Synthesis and Regulation and in the Retina 63 4.4 Dopamine: Site of Action and Signaling 64 4.5 Role of Melatonin and Dopamine in the Regulation of Retinal Functions 65 4.6 Melatonin and Dopamine as a Key Regulator of Retinal Circadian Rhythms 66 4.7 Conclusions 70 References 71 Chapter 5: Circadian Organization of the Vertebrate Retina 78 5.1 Molecular Organization of the Retinal Circadian Clock 80 5.1.1 Retinal Circadian Rhythms Are Generated by a Network of Clock Genes 80 5.1.2 Clock Genes Are Widely Expressed in the Retina and RPE 81 5.1.3 Genetic Disruption of the Clock Gene Network Disrupts Retinal Circadian Rhythms 82 5.2 Cellular Organization of the Retinal Circadian Clock 83 5.2.1 Generation of Retinal Circadian Rhythms Is Distributed Among Many Cell Types 83 5.3 Neurochemical Organization of the Retinal Circadian Clock 87 5.3.1 Intercellular Coupling May Not Be Necessary for Rhythms Generation 87 5.3.2 Entrainment of the Retinal Clock Involves Intraretinal Signaling by Dopamine 88 5.3.3 GABA Signaling Influences the Amplitude of Retinal Circadian Rhythms 90 5.4 Outputs of the Retinal Circadian Clock 91 5.4.1 The Retinal Clock Makes Both Intraretinal and Extraretinal Outputs 91 5.4.2 Melatonin 91 5.4.3 Dopamine 92 5.4.4 Gene Expression 92 5.4.5 Signaling by the Retinal Clock to the Brain 93 5.5 The Retinal Clock’s Role in Vision 93 5.6 The Retinal Clock’s Potential Role in Eye Disease 95 5.7 Summary 96 References 97 Chapter 6: Rhythmicity of the Retinal Pigment Epithelium 104 6.1 Maintenance of Retinal Health and Function by Activities of the RPE 105 6.2 A Conserved Role of the RPE in Outer Segment Renewal of Both Rods and Cones 107 6.3 Distinct Diurnal Rhythms of RPE Phagocytosis of Rod and Cone POS 107 6.4 Local and Central Mechanisms Controlling the Phagocytosis Rhythm of the RPE 109 6.5 The Molecular Mechanisms Governing Rhythmic RPE Phagocytosis 111 6.6 Dependence of the Rhythm of POS Shedding on the Rhythm of RPE Phagocytosis 114 6.7 Importance of the Diurnal RPE Phagocytic Rhythm for Retinal Health 116 6.8 Summary 117 References 117 Chapter 7: Retinal Circadian Rhythms in Mammals Revealed Using Electroretinography 122 7.1 Electroretinography 123 7.1.1 a-Wave 124 7.1.2 b-Wave 125 7.1.3 Oscillatory Potentials 125 7.1.4 Other Components 125 7.1.5 Separating Rod and Cone Responses 126 7.2 Rhythmicity of the ERG 127 7.2.1 Local Versus Central Clocks 127 7.2.2 ERG Rhythms in Human and Mouse 128 7.3 Mechanisms Underlying ERG Rhythmicity 129 7.3.1 Rod/Cone Pathway Balance 129 7.3.2 Melanopsin-Containing RGCs 129 7.3.3 Melatonin 130 7.3.4 Dopamine 131 7.3.4.1 Importance of Retinal Clocks for General Retinal Function 132 7.4 Ganglion Cell Rhythmicity 133 7.5 Conclusions 134 References 134 Chapter 8: Circadian Effects on Retinal Light Damage 139 8.1 Introduction 140 8.2 Retinal Morphology and Apoptotic Cell Death Following Light Exposure 140 8.3 Rhodopsin and Light-Induced Retinal Degeneration 142 8.4 Light-Induced Visual Cell Damage is Species-Dependent 143 8.5 Intense Light Induces Oxidative Stress in the Retina 143 8.6 Crystallins in the Retina and RPE Are Protective 144 8.7 Circadian Rhythms and Retinal Light Damage 145 8.8 Retinal Gene Expression Profiles and Analysis 148 8.9 Circadian Microarray Analysis 150 8.10 Relating Selected Retinal Genes to the Circadian Clock 151 8.11 Susceptibility and Resistance to Light-Induced Damage 167 8.12 Final Thoughts 172 References 172 Chapter 9: Circadian Rhythms and Vision in Zebrafish 179 9.1 Introduction 180 9.2 Morphological Rhythms 181 9.2.1 Photoreceptor Disc Shedding 181 9.2.2 Retinomotor Movements 181 9.2.3 Photoreceptor Synaptic Ribbons 183 9.2.4 Spinule Formation in Horizontal Cells 185 9.3 Physiological Rhythms 185 9.3.1 Behavioral Rhythms in Zebrafish 185 9.3.2 Visual Function and ERG Light Sensitivity in Adult Zebrafish 186 9.3.3 Visual Responses and Light Sensitivity in Larval Zebrafish 188 9.3.4 Circadian Rhythms in Horizontal Cells 190 9.3.5 Circadian Control of Photoreceptor Electrical Coupling 192 9.4 Clock Genetics in Zebrafish 193 9.4.1 Light-Sensitive Peripheral Oscillators 193 9.4.2 Clock Genes 193 9.4.3 Clock-Regulated Genes in the Retina 194 References 196 Chapter 10: Circadian Modulation of the Limulus Eye for Day and Night Vision 202 10.1 Introduction 203 10.2 Anatomical Organization of the Circadian System 204 10.3 Physiological Organization of the Circadian System 207 10.4 Circadian Rhythms in Retinal Structure and Function 211 10.5 Clock Influence on Visual Behavior 213 10.6 Conclusions 215 References 216 Chapter 11: Molluskan Ocular Pacemakers: Lessons Learned 220 11.1 Introduction 220 11.2 Lesson One: Central Clock Neural Rhythms Are “Diurnal” Whereas Circadian Behaviors Are Nocturnal or Diurnal 222 11.3 Lesson Two: Circadian Entrainment Occurs via Nontraditional Photoreceptors 222 11.4 Lesson Three: Single Neurons Can Act as Circadian Clocks 224 11.5 Lesson Four: Clock Neuron Rhythms Are Expressed via Modulation of Potassium Conductances 225 11.6 Lesson Five: Clock Synchronization by Light Occurs via Clock Neuron Membrane Depolarization and a Calcium Flux 226 11.7 Lesson Six: Clock Neuron Rhythms Are Modulated by Efferent Signals 227 11.8 Lesson Seven: Bilateral Coupling of the Central Clocks Helps Maintain Internal Synchrony 229 11.9 Lesson Eight: Regulation of a Transmembrane Ca 2+ Flux Represents a Common Pathway for Clock Phase Control 231 11.10 Lesson Nine: The Circadian Cycle in Clock Neurons Requires Daily Transcription and Translation as Part of the Timing Loop 232 11.11 Lesson Ten: Age-Driven Changes Occur in the Central Clock 233 11.12 Concluding Remarks 234 References 234 Index 240 The retina plays a critical role in the organization of the circadian system by synchronizing the brain's central clock with the external day through transduction of the daily light/dark cycle.¡ However, the substantial variation in luminance imposed on the retina between day and night also poses a challenge to its role as a sensory tissue - how is it possible to faithfully encode the enormous dynamic range of luminance that can exceed 10 orders of magnitude? The Retina and Circadian Rhythms summarizes the knowledge accumulated over the last 30 years about the organization of the retinal circadian clock in many different species, concentrating on the roles that this circadian system plays in retinal function. About the Series: The Springer Series in Vision Research is a comprehensive update and overview of cutting edge vision research, exploring, in depth, current breakthroughs at a conceptual level. It details the whole visual system, from molecular processes to anatomy, physiology and behavior and covers both invertebrate and vertebrate organisms from terrestrial and aquatic habitats. Each book in the Series is aimed at all individuals with interests in vision including advanced graduate students, post-doctoral researchers, established vision scientists and clinical investigators. The series editors are N. Justin Marshall, Queensland Brain Institute, The University of Queensland, Australia and Shaun P. Collin, Neuroecology Group within the School of Animal Biology and the Oceans Institute at the University of Western Australia Front Matter....Pages i-viii Introduction....Pages 1-2 Fundamental Retinal Circuitry for Circadian Rhythms....Pages 3-26 Circadian Photoreception: From Phototransduction to Behaviour....Pages 27-48 Role of Melatonin and Dopamine in the Regulation of Retinal Circadian Rhythms....Pages 49-68 Circadian Organization of the Vertebrate Retina....Pages 69-94 Rhythmicity of the Retinal Pigment Epithelium....Pages 95-112 Retinal Circadian Rhythms in Mammals Revealed Using Electroretinography....Pages 113-129 Circadian Effects on Retinal Light Damage....Pages 131-170 Circadian Rhythms and Vision in Zebrafish....Pages 171-193 Circadian Modulation of the Limulus Eye for Day and Night Vision....Pages 195-212 Molluskan Ocular Pacemakers: Lessons Learned....Pages 213-232 Back Matter....Pages 233-238