- •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
15
Luminous Efficiency Functions
Lindsay T. Sharpe and Andrew Stockman
CONTENTS
INTRODUCTION
SCOTOPIC (ROD) LUMINOUS EFFICIENCY FUNCTION
PHOTOPIC (CONE) LUMINOUS EFFICIENCY FUNCTION
MESOPIC (ROD-CONE) LUMINOUS EFFICIENCY FUNCTIONS
INDIVIDUAL DIFFERENCES INFLUENCING LUMINOUS EFFICIENCY
CONCLUSIONS
REFERENCES
INTRODUCTION
The Need for Luminous Efficiency
The human visual system operates over an effective range of 11 log10 units of radiant energy: from dim starlight, for which as few as 7 photon absorptions in separate rod photoreceptors suffice for threshold detection [1], to intense sunlight, for which the absorption of as many as 106 photons per cone photoreceptor per second bleaches almost all the photopigment and dazzles the observer [2]. The range is divided into three regions according to which of the two types of photoreceptors, the rods or cones, are functioning. The scotopic or dimmest region, within which only rods operate, includes the light levels between absolute rod threshold and absolute cone threshold. The mesopic or middle region, within which both rods and cones operate, includes the levels between cone threshold and rod saturation. And, the photopic or brightest region, within which only cones operate, includes the levels between rod saturation and the highest bleaching levels (see Fig. 1).
Within each region, lights generally increase in apparent brightness with increasing radiance. However, radiance is not directly related to brightness because the individual wavelengths of visible radiant energy do not contribute equally to the overall brightness sensation. In general, wavelengths in the middle of the spectrum, corresponding perceptually to what we call greens, are much more visually effective than those at the spectral extremes, corresponding perceptually to what we call violets and reds (see Chapter 14 on human cone spectral sensitivity and color vision deficiencies).
From: Ophthalmology Research: Visual Transduction and Non-Visual Light Perception
Edited by: J. Tombran-Tink and C. J. Barnstable © Humana Press, Totowa, NJ
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Fig. 1. Illumination levels. Typical ambient light levels are compared with photopic luminance (log cd m−2), mean pupil diameter (mm), photopic and scotopic retinal illuminance (log photopic and scotopic trolands, respectively), and visual function. The scotopic, mesopic, and photopic regions are defined according to whether rods alone, rods and cones, or cones alone operate. The conversion from photopic to scotopic values assumes a white standard CIE (Commission Internationale de l’ Éclairage, International Lighting Commission) D65 illumination. (Based on the design of Hood and Finkelstein, [155].)
The goal of visually relevant light specification (photometry) is to provide a practical method of measuring and specifying the apparent perceived intensity of any monochromatic or spectrally broad-band light or mixtures thereof. This seemingly simple goal, however, is difficult to accomplish because the human visual system as a whole, unlike a typical radiometric detector, does not respond univariantly to light. First, rods and cones do not have the same spectral sensitivities: When measured in vivo, the sensitivities of the rods and the short-wavelength-sensitive (S), middle-wavelength-sensitive (M), and long-wavelength-sensitive (L) cones are displaced relative to one another and peak at about 507 and 440, 545, and 565 nm, respectively. Thus, different spectral luminous efficiency functions have to be defined for the different ranges of human vision: the scotopic luminous efficiency function mediated exclusively by the rods, the photopic luminous efficiency function mediated exclusively by the cones (predominantly
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Fig. 2. Scotopic [CIE (Commission Internationale de l’ Éclairage, International Lighting Commission) 1951 V′(λ), black line] and photopic [V*(λ) function, gray line, [44] ] luminosity functions. The scotopic function is mediated exclusively by the rods; the photopic function is mediated by a linear combination of the L and M cones. The M-cone (long dashed line) and L- cone (short dashed line) spectral sensitivities [23] are also shown, plotted so that their weighted sum equals V *(λ).
the L and M cones), and the mesopic luminous efficiency function mediated by both the rods and cones. Figure 2 allows a comparison between representative scotopic (rod) and photopic (a weighted combination of the L- and M-cone sensitivities) spectral luminous efficiency functions. Second, the relative contributions of the different photoreceptor types to apparent intensity are strongly dependent on chromatic adaptation and other stimulus parameters, such as wavelength, temporal frequency, retinal location, and spatial frequency. These contributions are complicated by the existence of multiple postreceptoral channels that process the cone signals, which include the additive, luminance channel (L + M), and spectrally opponent chromatic channels (L − M) or (S − [L + M]) (e.g., [3–10]).
The essential element in converting radiometric measures (such as radiance) to photometric ones (such as luminance) is the derivation of a spectral luminous efficiency (luminosity) function, which defines the relative visual “effectiveness” of lights of different wavelength in specific matching or detection tasks. It is a dimensionless scalar or weighting function, normalized to a maximal value of unity. Dimensions are introduced by defining the luminous efficacy of the monochromatic radiant flux of the maximal value (see, e.g., [11, 12]). The choice of measurement task is crucial in defining luminous efficiency. For photometry to be as practicable as radiometry, the measured luminous efficiency of any mixture of lights must equal the sum of the luminous efficiencies of the component lights. Such additivity is known as obedience
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to Abney’s law [13, 14]. The requirement for additivity typically means that the designated photometric or psychophysical task favors postreceptoral visual mechanisms that are themselves approximately additive, such as the luminance pathway.
Psychophysical Measures of Luminous Efficiency
The measurement of scotopic luminous efficiency is relatively straightforward because it depends on the activity of a single photoreceptor type, the rods. Since photoreceptors are univariant and additive (see the section on univariance), any technique that maintains rod isolation should yield additive measures of luminous efficiency. Obtaining additive measures of photopic and mesopic luminous efficiency is more challenging because, as noted, multiple photoreceptors and postreceptoral channels can be involved.
Many different psychophysical techniques have been used to estimate the photopic spectral luminous efficiency function, including heterochromatic flicker photometry (HFP), heterochromatic modulation photometry (HMP), minimally distinct border (MDB), minimum motion, direct heterochromatic brightness matching (HBM), step- by-step brightness matching, color matching, absolute threshold, increment threshold, critical flicker fusion (CFF), and visual acuity. Confusingly, many of these different procedures and criteria yield very different results (for reviews, see [12, 15–23]).
Broadly, the photopic techniques can be divided between those that produce an additive spectral luminous efficiency function and obey Abney’s law and those that do not. Those that do not obey Abney’s law are impractical for photometry and can be largely discarded, although they may have some limited application to specific viewing situations. Those that do include HFP, HMP, MDB, CFF, and minimum motion (e.g., [7, 16, 19, 20, 24, 25]). These additive techniques have in common the use of high temporal or spatial frequencies, which discriminate against the influence of signals from the short-wavelength-sensitive or S-cone pathways or signals in other chromatic pathways and favor signals from the additive, luminance pathway, which sums signals from the L and M cones. For example, in HFP, superimposed lights alternating at moderate-to-high temporal rates are adjusted to minimize the perception of flicker, while in MDB abutting side-by-side lights are adjusted to make the border between them appear minimally distinct.
Factors that Influence Luminous Efficiency
Even if we restrict our consideration to techniques that yield additive efficiency measurements, other factors need to be taken into account when specifying a standard spectral luminous efficiency function. One important factor is the sizable individual differences in spectral luminous efficiency that are found between observers due to individual variability in preretinal screening and photopigment optical density, both of which change with aging. These are discussed in more detail in a separate section. To define a standard, mean spectral luminous efficiency function for photometry, many subjects must be used in its derivation, so that the mean data are representative of the population as a whole (although distinct functions may have to be derived for different age groups). It is, however, important to recognize that the mean standard functions are unlikely to apply to most individual observers. Nonetheless, corrections, such as those outlined in the section on individual differences influencing luminous efficiency, can be made to the mean functions to make them more representative of the individual observer.
