- •An Organ of Exquisite Perfection
- •Optical Path
- •Retinal Photoreception
- •Photoreception Optics
- •Photoreception Biochemistry
- •Membrane Voltages
- •Blind Spot
- •Retinal Pathways
- •Through Pathway
- •Receptive Fields
- •Lateral Pathway
- •Retinal Ganglion Cells
- •Retinal Glia
- •References
- •Development of the Foveal Specialization
- •Introduction
- •Foveal Development
- •Specification of Foveal Location
- •Formation of a Rod-Free Zone
- •Cones, Ganglion Cells, and Initial Pit Formation
- •Deep Foveal Pit Formation
- •Foveal Hypoplasia
- •Conclusions and Perspectives
- •Acknowledgments
- •References
- •An Update on the Regulation of Rod Photoreceptor Development
- •Introduction
- •Brief Overview of Retinal Development and Early Stages of Rod Photoreceptor Differentiation
- •Transcription Factors
- •Basic Helix-Loop-Helix Genes
- •Nuclear Receptors
- •Retinoic Acid/Retinoic Acid Receptors
- •Wnt/Frizzled Pathway
- •Taurine
- •Ciliary Neurotrophic Factor/Leukemia Inhibitory Factor/Pleiotrophin/Signal Transducer and Activators of Transcription 3/SOCS
- •Conclusions and Future Prospects
- •References
- •Introduction
- •Retinal Adhesion
- •Physiology of Retinal Adhesion
- •Molecular Mechanisms of Retinal Adhesion
- •Significance of Retinal Adhesion for Retinal Function
- •Photoreceptor Outer Segment Renewal
- •Physiology of Outer Segment Disk Assembly and Disk Shedding
- •Physiology of RPE Engulfment of Shed Outer Segment Fragments
- •Molecular Mechanisms of Shedding and RPE Phagocytosis
- •Significance of Photoreceptor Outer Segment Renewal for Retinal Function
- •Perspective
- •Acknowledgments
- •References
- •Molecular Biology of IRBP and Its Role in the Visual Cycle
- •Introduction
- •IRBP Protein Studies
- •IRBP Null Mice
- •IRBP Induces Experimental Autoimmune Uveitis
- •IRBP Expression During Development
- •Variability in IRBP Expression
- •Molecular Biology of IRBP
- •IRBP Genomic Cloning
- •Evolution of IRBP
- •Identification of DNA cis-Acting Controlling Elements: In Vitro and In Vivo Experiments
- •Transcription Factors and their Role in the Control of IRBP Expression
- •Rx/rax Transcription Factor
- •NrL Transcription Factor
- •Crx Transcription Factor
- •OTX2 Transcription Factor
- •Transgenic Mice
- •Repressors of IRBP Gene Expression
- •Summary and Conjecture
- •Acknowledgments
- •References
- •Regulation of Photoresponses by Phosphorylation
- •Introduction
- •Cone-Specific Kinase, GRK7
- •Protein Kinase C
- •Cyclin-Dependent Kinase
- •Tyrosine Kinases
- •Protein Phosphatases
- •Conclusion
- •References
- •The cGMP Signaling Pathway in Retinal Photoreceptors and the Central Role of Photoreceptor Phosphodiesterase (PDE6)
- •Regulation of Intracellular cGMP Levels in Photoreceptor Cells
- •Downstream Targets of cGMP Action in Photoreceptor Cells
- •cGMP-Dependent Protein Kinase
- •Cyclic Nucleotide-Gated Ion Channels
- •PDE6 Is a High-Affinity cGMP-Binding Protein
- •Compartmentation of cGMP Signaling in Photoreceptor Outer Segments
- •Physiology of the Photoreceptor Response to Light
- •Biochemical Cascade of Visual Excitation
- •Central Components of the cGMP Signaling Pathway
- •Termination and Adaptation of the Light Response
- •Deactivation of Rhodopsin
- •Deactivation of Transducin
- •Deactivation of PDE6
- •Activation of GC
- •Regulation of the CNG Ion Channel
- •Photoreceptor PDE (PDE6) Structure and Function
- •The Cyclic Nucleotide Phosphodiesterase Superfamily
- •Subunit Composition of Rod and Cone PDE6 Holoenzyme
- •Catalytic Subunit
- •Regulatory GAF Domain
- •Catalytic Domain
- •C-Terminal Prenylation
- •PDE6 Has Evolved to Meet the Special Demands of the Central Effector of Visual Transduction
- •PDE6 Regulation
- •Transducin Activation of Rod PDE6 During Visual Excitation
- •Functions of the Regulatory cGMP-Binding GAF Domains of PDE6
- •Potential PDE6 Regulatory Binding Proteins
- •Glutamic Acid-Rich Protein 2
- •Conclusions
- •Acknowledgments
- •References
- •Rhodopsin Structure, Function, and Involvement in Retinitis Pigmentosa
- •Introduction
- •Historical Perspective
- •Rhodopsin, Localization, and Signaling
- •Dark State and Activation
- •Structural Analysis
- •Electron Cryomicroscopy and Crystal Structure
- •Nuclear Magnetic Resonance
- •Cysteine Mutagenesis and Electron Paramagnetic Resonance
- •Other Approaches
- •Retinitis Pigmentosa
- •Transmembrane RP Rhodopsin Mutants
- •Cytoplasmic RP Rhodopsin Mutants
- •Intradiskal RP Rhodopsin Mutants
- •Implications of Receptor Misfolding
- •Nongenetic Contributions to RP
- •Conclusion
- •References
- •Multiple Signaling Pathways Govern Calcium Homeostasis in Photoreceptor Inner Segments
- •Introduction
- •Overview of Ca2+ Regulation in the Inner Segment
- •Voltage-Operated Calcium Channels Play a Central Role in Inner Segment Calcium Regulation
- •Ca2+ Channels in Rods and Cones
- •Photoreceptor Malfunction and Degeneration
- •Therapeutic Strategies
- •Development
- •Acknowledgments
- •References
- •The Transduction Channels of Rod and Cone Photoreceptors
- •The Role of CNG Channels in Photoreceptor Physiology
- •The Activation Phase of the Light Response
- •Recovery After a Light Stimulus and Adaptation to Continuous Illumination
- •CNG Channels in the Synaptic Transmission of Cone Photoreceptors
- •The Molecular Composition of CNG Channels
- •The Basic Activation Properties of CNG Channels
- •Transmembrane Topology and Functional Domains
- •The Cyclic-Nucleotide-Binding Domain
- •The Amino Terminal Domain and Modulation by Calmodulin
- •The P Region
- •The GARP Domain of CNGB1
- •Modulation by Phosphorylation and All-trans Retinal
- •Synthesis, Maturation, and Targeting of CNG Channels
- •Visual Dysfunction Caused by Mutant CNG Channel Genes
- •References
- •Appendix
- •Visual Dysfunction Caused by Mutant CNG Channel Genes
- •Mutations in CNGA1 and CNGB1 Associated with Retinitis Pigmentosa
- •Mutations in CNGA3 and CNGB3 Associated with Cone Dysfunction
- •References
- •Rhodopsins in Drosophila Color Vision
- •Introduction
- •Anatomy and Molecular Aspects of Color-Sensitive Opsins in the Drosophila Eye
- •Structure of the Drosophila Eye: Ommatidia, Photoreceptors, and Rhodopsins
- •Molecular Genetics and Evolution of Rh5 and Rh6
- •Development and Patterning of Rhodopsins for Drosophila Color Vision
- •Mutually Exclusive Rhodopsin Expression
- •Transcription Factors Specify Outer from Inner Photoreceptors and Distinguish R7 from R8
- •A Stochastic Decision Induces Rhodopsins in R7 Photoreceptor
- •A Bistable Feedback Loop Specifies R8 Photoreceptor Subtype and Expression of Rh5 and Rh6
- •Comparison Between Mammalian and Drosophila Color Vision Rhodopsins
- •Human Color-Sensitive Opsins
- •Conclusion
- •References
- •INAD Signaling Complex of Drosophila Photoreceptors
- •Introduction
- •Identification of the INAD Signaling Complex
- •Function of the INAD Signaling Complex
- •Information Transfer From Rhodopsin to the Signaling Complex BY the Visual G Protein
- •Signaling Complexes in Vertebrate Photoreceptor Cells
- •Acknowledgments
- •References
- •Visual Signal Processing in the Inner Retina
- •Introduction
- •Visual Information is First Processed in the OPL
- •Bipolar Cells form Parallel Pathways and Provide Excitatory Input to the IPL
- •Functional Stratification of the IPL
- •ON and OFF Response Stratification
- •Sustained and Transient Response Stratification
- •Synaptic Mechanisms Shape Excitatory Signals in the IPL
- •Glutamate Release Is Tonic and Graded
- •Transporters Terminate Excitatory Signaling to Ganglion Cells
- •Postsynaptic Glutamate Receptor Properties Shape Ganglion Cell Excitation
- •Modulating Glutamate Release Shapes Excitatory Responses
- •Amacrine Cells Mediate Inhibition in the IPL
- •Presynaptic Inhibition
- •Asymmetric Presynaptic Inhibition
- •Presynaptic Inhibition Is Filtered by GABA Receptor Properties
- •Presynaptic Inhibition May Be Shaped by Transmitter Release Differences
- •Glycine, the Other Inhibitory Transmitter
- •Parallel Ganglion Cell Output Pathways
- •Ganglion Cells Encode Color Information
- •Directional-Selective Ganglion Cells
- •Intrinsically Photosensitive Ganglion Cells
- •Conclusions
- •References
- •Human Cone Spectral Sensitivities and Color Vision Deficiencies
- •Introduction
- •Overview
- •Transduction
- •Univariance, Monochromacy, Dichromacy, and Trichromacy
- •Trichromacy and Color-Matching Functions
- •Cone Spectral Sensitivities
- •Introduction
- •Cone Spectral Sensitivity Measurements
- •From Cone Spectral Sensitivities to Color-Matching Functions
- •Other Factors That Influence Spectral Sensitivity
- •Lens Pigment
- •Macular Pigment
- •Photopigment Optical Density
- •Changes with Eccentricity
- •Congenital Color Vision Deficiencies
- •Protan and Deutan Defects
- •Protanopia and Deuteranopia
- •Photopigment Variability and Protanomaly and Deuteranomaly
- •Tritanopia
- •Monochromacies
- •Cone Monochromacies
- •Rod Monochromacy
- •Conclusions
- •Acknowledgment
- •References
- •Luminous Efficiency Functions
- •Introduction
- •The Need for Luminous Efficiency
- •Psychophysical Measures of Luminous Efficiency
- •Factors that Influence Luminous Efficiency
- •Scotopic (Rod) Luminous Efficiency Function
- •Introduction
- •Univariance
- •International Standard
- •Photopic (Cone) Luminous Efficiency Function
- •Introduction
- •International Standards
- •Other Photopic (Nonadditive) Luminous Efficiency Functions
- •Mesopic (Rod-Cone) Luminous Efficiency Functions
- •Introduction
- •Models of Mesopic Luminous Efficiency
- •International Standard
- •Individual Differences Influencing Luminous Efficiency
- •Attenuation of Spectral Light by the Lens and Other Ocular Media
- •Attenuation of Spectral Light by the Macular Pigment
- •Optical Densities of the Photopigments
- •Relative Numbers of L and M Cones
- •Cone Pigment Polymorphisms
- •Directional Sensitivity
- •Variations in the Contribution of Chromatic Channels
- •Conclusions
- •References
- •Cone Pigments and Vision in the Mouse
- •Introduction
- •Prevalence and Spatial Distribution of Mouse Cones
- •Mouse Strain Variations
- •Mouse Cone Pigments
- •Cone Pigment Spectra
- •Evolution and Spectral Tuning of Mouse Cone Pigments
- •Regional Distribution of Mouse Cone Pigments
- •Expression of Mouse Cone Pigments
- •Cone Signal Pathways in the Mouse Retina
- •Cone-Based Vision in Mice
- •Assessment Techniques
- •Spectral Sensitivity
- •Spatial and Temporal Sensitivity
- •Color Vision
- •Targeted Deletions of Rods or Cones
- •Addition of New Cone Pigments
- •Mouse and Human Cone Vision
- •Acknowledgment
- •References
- •Multifocal Oscillatory Potentials of the Human Retina
- •Introduction
- •Recording Techniques
- •Underlying Mechanisms
- •The Influence of age and Gender
- •Disease-Related Changes
- •Origins of Single Potentials
- •Dichromats
- •Congenital Stationary Night Blindness
- •Topographical Alterations
- •Diabetes
- •Retinal Vessel Occlusion
- •Glaucoma
- •General Alterations
- •Vigabatrin Treatment
- •Conclusion
- •References
- •The Aging of the Retina
- •Introduction
- •Morphological Alterations
- •Neural Changes
- •Retinal Pigment Epithelium and Lipofuscin Formation
- •Bruch’s Membrane and Choroid
- •Retinal Function Changes
- •Age-Related Macular Disease
- •Conclusions
- •References
- •Aging of the Retinal Pigment Epithelium
- •Introduction
- •Aging Changes In the Fundus
- •Age-Related Changes In RPE Morphology
- •Melanosomes
- •Lipofuscin
- •Pigment Complexes
- •Mitochondria
- •Bruch’s Membrane
- •Functional Consequences of RPE Cell Aging
- •Phagocytic Load
- •The Effect of Lipofuscin on the RPE
- •Melanosomes
- •Antioxidant Capacity of the RPE
- •Lysosomal Enzyme Activity
- •Mitochondrial Damage in the RPE
- •Bruch’s Membrane Aging
- •Oxidative Stress and RPE Aging
- •The Relationship Between Aging and Retinal Pathologies
- •Summary and Conclusions
- •References
- •Visual Transduction and Age-Related Changes in Lipofuscin
- •Introduction: What is Lipofuscin?
- •Lipofuscin of the Retinal Pigment Epithelium
- •Composition of RPE Lipofuscin
- •Fluorescence Properties of RPE Lipofuscin
- •A2E as a Marker of Lipofuscin Accumulation
- •Factors Affecting Accumulation of RPE Lipofuscin
- •Phagocytosis and Autophagy
- •Role of Lysosomal Degradation
- •Role of Oxidative Stress
- •Role of Phototransduction in Accumulation of RPE Lipofuscin
- •Transient Buildup of All-trans Retinal in Photoreceptor Outer Segments as a Critical Factor for Lipofuscin Formation
- •Inhibition of the Retinoid Cycle Inhibits Lipofuscin Accumulation
- •Role of Exposure of the Retina to Light
- •Other Factors Contributing to Accelerated Accumulation of RPE Lipofuscin
- •A Hypothetical Scenario of Biogenesis of RPE Lipofuscin
- •Effects of Lipofuscin on RPE Function and Viability
- •Photoreactivity of RPE Lipofuscin
- •Toxicity of RPE Lipofuscin
- •Effects of Lipofuscin Components and Oxidative Stress in the RPE on Proinflammatory and Angiogenic Signaling
- •Approaches to Diminish Lipofuscin Accumulation or Lipofuscin-Induced Damage
- •Conclusions
- •References
- •A Nonspecific System Provides Nonphotic Information for the Biological Clock
- •Introduction
- •Nonphotic Information
- •Nonspecific Systems
- •Ascending Reticular-Activating System
- •Orexin/Hypocretin Projection
- •Intergeniculate Leaflet of the Thalamus
- •Anatomy
- •The Pharmacology of the IGL
- •Chronobiology
- •The Electrophysiology of the IGL
- •IGL as an Integrator of Photic and Nonphotic Information
- •Conclusions
- •References
- •The Circadian Clock: Physiology, Genes, and Disease
- •Introduction
- •Circadian Rhythms in Physiology and Behavior
- •Circadian Rhythms in Visual Function
- •Entrainment
- •Anatomy
- •The Suprachiasmatic Nucleus
- •Inputs to the SCN
- •Peripheral Oscillators
- •A Clock in the Eye
- •Oscillators Outside the Nervous System
- •Clock Genes
- •Human Implications
- •Summary
- •References
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