Adler's Physiology of the Eye

Front Cover
Title Page
Copyright Page
Preface
List of Contributors
Acknowledgements
Dedication
Section 1 - Focusing of an image on the retina
	1 Optics
		The young eye
			Relevant anatomy
				Axial length
				Emmetropization
				Retinal receptors
				Neural processing
			Relevant early physiology
				Recognizing faces
				Line orientation receptors
				Monitoring other’s eye movements
				Recognizing movement
			Summary – social seeing
		The image of the human adult eye
			Tuned to visible light waves
			Role of the cornea
			Role of the crystalline lens
			Accommodation
			Role of the retina
				Rhodopsin
				Receptor size and spacing
			Visual acuity testing
			Chart luminance
				Visual acuity as Log MAR
			Visual acuity chart contrast
				Contrast sensitivity testing
			Definition and units
				Contrast
				Contrast sensitivity
			Targets
			Sine waves
			Recording contrast sensitivity
			Glare, tissue light scattering, and contrast sensitivity
			Clinical conditions affecting glare and contrast sensitivity
				Optical conditions
				Corneal conditions
					Corneal edema
					Contact lens wear
					Keratoconus
					Nephrotic cystinosis
					Penetrating keratoplasty
					Refractive surgery
					Cataracts and opacified posterior capsules
					Modulation transfer function
					Depth of focus
				Optical aberrations
					Light scattering
					Natural defenses against light scattering
			Chromatic aberrations
			Spherical aberration
			Light absorption
			Summary – a compromise of eye function
		The aging eye
			Evolution of ocular components
			Non-optical brain mechanisms that enhance the retinal image
			Contrast enhancement
				Edge sharpening
				Vernier acuity
				Removing distractions
			Refractive errors
				Prevalence
			Myopia
				Pathologic myopia
				Physiologic, or school, myopia
			Astigmatism
			Presbyopia
				Components of ametropia
		References
	2 Optical Aberrations and Wavefront Sensing
		Introduction
		Optical aberrations
			Wavefront optics
			Optical limitations to vision
			Aberrations
				Chromatic aberrations
				Monochromatic aberrations
		Measuring optical aberrations
			Aberrometry and wavefront sensing devices
				Wavefront sensing devices
		Correcting higher-order aberrations
			Visual disturbances associated with HOA
			Visual performance after correcting HOA
			Factors which limit the benefit of HOA correction
		Clinical applications of wavefront aberration correction
			Corneal ablations
			Correcting HOA with spectacles, contact lenses and intraocular lenses
		References
	3 Accommodation
		Introduction
		Accommodation
		Optics of the eye
		The optical requirements for accommodation
		Depth of field
		Visual acuity
		The anatomy of the accommodative apparatus
			The ciliary body
			The ciliary muscle
				The zonular fibers
				The lens capsule
				The crystalline lens
		The mechanism of accommodation
		Accommodative optical changes in the lens and eye
		The stimulus to accommodate
		The pharmacology of accommodation
		Measurement of accommodation
		Presbyopia
		Factors contributing to presbyopia
			Age-related changes in rhesus ciliary muscle
			Age-related changes in human ciliary muscle
			Age-related changes in the zonule
			Age-related changes in the capsule
			Growth of the crystalline lens
			Loss of ability of the human lens to accommodate
			Age-related increase in stiffness of the human lens
		References
Section 2 - Physiology of optical media
	4 Cornea and Sclera
		Introduction
		Cornea
			Embryology, growth, development, and aging
			Major corneal reference points and measurements
			Optical properties
				Light refraction
				Light transmission
					Collagen
					Keratocytes
					Proteoglycans
					Corneal nerves
					Corneal stromal wound healing
			Barrier properties
				Low-permeability barrier: the corneal epithelium
				High-permeability barrier: the corneal endothelium
					Leaky barrier function
					Metabolic pump function
					Corneal edema
					Basement membrane and glycocalyx
			Mechanical properties
				Corneal stress
				Corneal stiffness, strength extensibility, and toughness
				Chronic biomechanical failure of the cornea – ectasia
			Other functions
				Drug delivery
				Ultraviolet light filtration
		Sclera
			Embryology, growth, development, and aging
			Major scleral reference points and measurements
			Mechanical properties
				Scleral dehydration and edema
				Episcleral vasculature
				Wound healing
			Drug delivery
		Acknowledgments
		References
	5 The Lens
		The anatomy of the adult lens
			The basics of lens refraction and transparency
		The early development of the lens
		Lens fiber cell differentiation
			Lens crystallins
			The lens fiber cell cytoskeleton
				Other cellular and biochemical specializations found in lens fiber cells
			The control of lens growth
			Communication between lens epithelial and fiber cells
			Vascular support during lens development
			The lens as the organizer of the anterior segment
		Special problems of lens cell metabolism
			Overview
			Oxidants within and around the lens
			Protection against oxidative damage
		Energy production in the lens
		Water and electrolyte balance
		Lens transparency and refraction
		Changes in the lens with aging
		The structure and development of the lens sutures
		The lens capsule
		The zonules
		Cataracts
			Cataract epidemiology
				General risk factors
			Age-related nuclear cataracts
			Age-related cortical cataracts
			Posterior subcapsular cataracts
			Mixed cataracts
			Secondary cataracts
			Less common types of cataract
		Overview of age-related cataract formation
		Perspectives for preventing cataract blindness
		Acknowledgments
		References
	6 The Vitreous
		Introduction
		Anatomy
			Embryology
				Structural considerations of embryology
				Molecular and cellular considerations of embryology
			Anatomy of the mature vitreous body
				The vitreoretinal interface
		Ultrastructural, biochemical, and biophysical aspects
			Ultrastructural and biochemical aspects
			Biophysical aspects
		Aging of the vitreous
			Molecular mechanisms in aging
			Structural changes
			Vitreo–retinal interface imaging
				Diffusion kinetics as an indicator of the biophysical status of the vitreous
		Physiology of the vitreous body
			Support function for the retina and filling up function of the vitreous body cavity
				Normal conditions
				Pathological/pathophysiological correlations
					Posterior vitreous detachment
					Development of macular edema
			Diffusion barrier between the anterior and the posterior segments of the eye
				Normal conditions
				Pathological/pathophysiological correlations
			Metabolic buffer function
				Normal conditions
				Pathological/pathophysiological correlations
			Establishment of an unhindered path of light
				Normal function
				Pathological/pathophysiological correlations
		The vitreous body as a sensor for the physiology of surrounding structures
			Determination of the blood–retinal barrier, passive permeability and active transport for fluorescein in humans, based upon concentration changes in the vitreous body
		Concluding remarks
		Acknowledgments
		References
Section 3 - Direction of gaze
	7 The Extraocular Muscles
		The bony orbit
		Normal extraocular muscles
			Gross anatomy
			Cranial motor nerve innervation
			Orbital connective tissue
			Histological anatomy and physiologic implications
			Metabolism
			Proprioception and proprioceptors
			Development
			Disease propensity
		Disorders of eye movements
			Strabismus
			Nystagmus
			Congenital cranial dysinnervation disorders (CCDD)
		Diseases where EOM are preferentially spared
		Diseases where EOM are preferentially involved
		Conclusion
		References
	8 Three-Dimensional Rotations of the Eye
		Eye motility
		Quantifying eye rotations
			Nested-axes coordinates
			Head-fixed coordinates
		Listing’s law
			False torsion
		Neural control of ocular orientation
		Orbital mechanics can simplify neural control: extraocular pulleys
		Summary
		References
	9 Neural Control of Eye Movements
		Introduction
			Three fundamental visual sensory-motor tasks
			Three components of eye rotation
				Binocular constraints on eye position control
				Feedback and feedforward control systems
				Hierarchy of oculomotor control
		Final common pathway
			Cranial nerves: III, IV, & VI and motor nuclei
			Motor neuron response
		Functional classification into three general categories
			Stabilization of gaze relative to the external world
				Extra-retinal signals
				Retinal signals
				Neuro-control of stabilization reflexes
					Vestibulo-ocular reflex
					Optokinetic nystagmus
			Foveal gaze lock (maintenance of foveal alignment with stationary and slowly moving targets)
				Static control of eye alignment (fixation)
				Dynamic control of eye alignment (smooth tracking responses to open- and closed-loop stimuli)
					Conjugate smooth pursuit tracking
					Disconjugate smooth vergence tracking
					Adaptable interactions between smooth pursuit and smooth vergence
				Neuro-control of smooth foveal tracking
					Smooth pursuit tracking system
					Smooth vergence tracking system
			Foveal gaze shifts: target selection and foveal acquisition
				Rapid conjugate shifts of gaze direction (saccadic eye movements)
				Disconjugate shifts of gaze distance (the near response in symmetrical convergence)
				Interactions between conjugate and disconjugate eye movements (asymmetric vergence)
				Neuro-control of foveal gaze shifts
					Saccadic gaze shifting system
					Vergence gaze shifting system: the near triad and interactions with saccades
		Neurological disorders of the oculomotor system
			Strabismus
			Gaze restrictions
			Saccade disorders
			Nystagmus
		Acknowledgments
		References
Section 4 - Nutrition of the eye
	10 Ocular Circulation
		Introduction
		Anatomy of the ocular circulation
			Vascular supply of the retina
			Vascular supply of the choroid
				Paraoptic pattern
				Perimacular pattern
			Fine structure and innervation of retinal and choroidal vessels
			Vascular supply of the anterior segment
			Transport through blood–retinal barriers
				Transcellular pathway (transcytosis)
				Paracellular pathway
			Extracellular structures
				Glycocalyx
				Extracellular matrix
			Inner blood–retinal barrier
				Pericytes
				Glial cells
			Outer blood–retinal barrier
				Fenestrated endothelium
				Retinal pigment epithelium
				Bruch’s membrane
			Blood–aqueous barriers
		Techniques for measuring ocular blood flow
			Techniques used in experimental animals
			Non-invasive techniques used in physiological and clinical research
		Ocular circulatory physiology
			General hemodynamic considerations
			Ocular hemodynamic data under basal physiological conditions
				Retina
				Choroid
				Ciliary circulation
				Vasomotion
				Effects of age on ocular blood flow
		Regulation of ocular BF
			Autoregulation of ocular blood flow
				Retina and ONH
				Choroid
				Anterior uvea
			Mechanisms underlying retinal and ONH autoregulation
			Regulation of blood flow in response to increase in arterial blood pressure (ABP)
				Static exercises
				Dynamic exercises
				Change in posture
			Regulation of blood flow in response to changes in blood gases
				Hyperoxia
				Hypoxia
				Hypercapnia
		Metabolic control of retinal blood flow
			Retinal metabolism and vasoreactivity
			Blood flow response to visual stimulation
				Light/dark transition
				Flicker
			Control of arterial tone by endothelium or neuro-glial activity
				Nitric oxide
				Endothelins
				Prostaglandins (PGs)
			Neural, endocrine, and paracrine control
				Effects of vasoactive nerves
				Adenosine
			Endogenous and pharmacological substances
				Role of administration route
				Vasoconstrictors
				Vasodilators
			Ciliary blood flow regulation
		Ocular blood flow and its regulation in diseases
			Diabetes
			Glaucoma
			Age-related macular degeneration
		References
	11 Production and Flow of Aqueous Humor
		Aqueous humor formation
			Physiology of aqueous humor formation
			Biochemistry of aqueous humor formation
		Aqueous humor composition
			Blood–aqueous barrier
			Active transport
		Pharmacology and regulation of aqueous humor formation and composition (Box 11.1)
			Cholinergic mechanisms
			Adrenergic mechanisms
			Other agents
		Aqueous humor drainage
			Fluid mechanics
			Structural components
				Pumping model for trabecular outflow
				Active involvement of the TM in regulating outflow
			Outflow obstruction
				Extracellular matrix accumulation and POAG
				Cell and other particulates
				Protein and other macromolecules
		Pharmacology and regulation of outflow
			Cholinergic mechanisms
				Conventional (trabecular) outflow
				Alterations in cholinergic sensitivity of the outflow apparatus
				Unconventional (uveoscleral) outflow
			Adrenergic mechanisms
				Conventional (trabecular) outflow
				Unconventional (uveoscleral) outflow
			Cytoskeletal and cell junctional mechanisms (Box 11.2)
			Corticosteroid mechanisms
			Prostaglandin mechanisms (Box 11.3)
			Cell volume related mechanisms
			Hyaluronidase and protease-induced facility increases
			Other agents
			Physical enhancement of outflow
		References
	12 Metabolic Interactions between Neurons and Glial Cells
		Introduction
		Retinal oxygen distribution and consumption
			Inner retina
			Dark and light O2 consumption
			Outer retina
			Photoreceptor QO2 in darkness
			Photoreceptor QO2 in light
		Role of glycolysis underlying retinal function: from whole retina to its parts
		Biochemical specialization of glial cells
		Role of glycogen
		Functional neuronal activity and division of metabolic labor
		Cellular compartmentation of energy substrates other than glucose
		Experimental models used to study the interaction between photoreceptors and glial Müller cells
			In vitro studies of the retina of the honeybee drone
				If there are no conventional synapses in drone retina and only the photoreceptors are directly excitable by light, what is the evidence that photoreceptors depend on surrounding glia for their metabolic needs?
				When bee retinal slices are exposed to the glycolytic poison IAA, the light-induced change in QO2 is gradually abolished. Is this modulation of QO2 a direct effect of IAA in photoreceptors?
				What is the evidence that photostimulation of drone retinal slices increases the carbohydrate metabolism in the glia to sustain photoreceptor respiration?
				Glucose is not the principal energy substrate used by photoreceptors, so what is the identity of the energy metabolite maintaining photoreceptor function and respiration?
				What is the biochemical evidence for the metabolic effects of NH4+and glutamate in glia?
			Overall scheme for metabolic compartmentation and metabolic trafficking in honeybee drone retina
				Experimental models in vertebrates
		Metabolic interactions between vertebrate photoreceptors and Müller glial cells
		Metabolic interaction between photoreceptors and retinal pigment epithelia
		Metabolic factors in the regulation of retinal blood flow
		Metabolic pathway leading to nitric oxide release
		References
	13 The Function of the Retinal Pigment Epithelium
		Introduction
		Absorption of light
		Transepithelial transport
			Transport from the blood side to the photoreceptor side
			Transport from the retinal side to the blood side
		Capacitative compensation of fast changes in the ion composition in the subretinal space
		Visual cycle
		Phagocytosis of photoreceptor outer segments
		Secretion
			Structural integrity of neighboring tissues
			Immune privilege of the eye
		References
Section 5 - Protection of the eye
	14 Functions of the Orbit and Eyelids
		Introduction
		Orbital anatomy and function
			Orbit osteology
			The orbital apex
			Orbital soft tissues
				Periorbital fascia
				Orbital fat
				Orbital nerves
				Vascular anatomy
					Arterial supply
					Venous drainage
				Orbital lymphatic drainage
		Facial and eyelid anatomy and function
			The eyebrow and forehead
			The midface
			The eyelid
				The eyelid margin
				Eyelid musculature
				Blinking
				Eyelid fat
				Eyelid vasculature
				Eyelid lymphatics
				Eyelid innervation
		References
	15 Formation and Function of the Tear Film
		Tear film overview
		Glycocalyx
			Structure
			Function
		Mucous layer
			Structure
			Conjunctival goblet cells
			Regulation of goblet cell mucin production
				Overview
				Regulation of goblet cell secretion
				Regulation of goblet cell proliferation
			Regulation of conjunctival electrolyte and water secretion
			Mucous layer function
		Aqueous layer
			Overview
			Lacrimal gland structure
			Lacrimal gland innervation
			Protein secretion regulation
				Types of protein secretion
				Cholinergic agonists
				VIP
				α1-Adrenergic agonists
				EGF
				Interaction of pathways
			Regulation of electrolyte and water secretion
				Mechanism of acinar electrolyte and water secretion
				Mechanism of ductal electrolyte and water secretion
				Neural activation of electrolyte and water secretion
			Lacrimal gland fluid composition
			Aqueous layer function
		Lipid layer
			Structure of meibomian glands and mechanism of lipid production
			Regulation of meibum secretion
				Neural regulation
				Hormonal regulation
			Function
		References
	16 Sensory Innervation of the Eye
		Introduction
		Anatomy of ocular sensory nerves
			Origin of the ocular sensory nerves
				Trigeminal ganglion neurons
				The ophthalmic nerve and its branches
			Distribution of sensory nerve fibers within the eye
			Architecture of corneal sensory nerves
				Corneal stromal nerves
				Subepithelial nerve plexus
				Sub-basal nerve plexus
				Intraepithelial nerve terminals
			Central sensory pathways
		Development and remodeling of corneal innervation
			Development of corneal nerves
			Dynamic remodeling of adult corneal innervation
			Regeneration of injured corneal nerves
		Functional characteristics of ocular sensory innervation
			Trigeminal ganglion neurons
				Sensory fibers of the cornea and conjunctiva
					Polymodal nociceptors
					Mechano-nociceptors
					Cold thermal receptors
					“Silent” nociceptors
				Sensory fibers of the sclera, iris, and ciliary body
				Ocular trigeminal ganglion neurons
			Central pathways
		Inflammation and injury effects on ocular sensory neurons
			Local inflammation
			Nerve injury
		Trophic effects of ocular sensory nerves
		Sensations arising from the eye
			Techniques for testing ocular surface sensitivity
			Psychophysics of corneal and conjunctival sensations
			Sensitivity of the injured cornea
		Ocular pain
			Superficial ocular pain
			Deep ocular pain
			Pain referred to the eye
		Drugs acting on ocular sensory nerves
			Topical anesthetics
			Anti-inflammatory drugs
			Cycloplegic agents
			Analgesics
			Prevention of surgical pain
		References
	17 Outward-Directed Transport
		Introduction
		Efflux transporters – brief history
		Efflux transporters in ocular tissues
			P-gp
				Mode of action and structure of P-gp
			MRP
				Mode of action and structure of MRP
			BCRP
				Mode of action and structure of BCRP
			LRP
			Localization of transporters
		Discussion
			Clinical correlates from literature
			Strategies to evade efflux transporters
		Acknowledgment
		References
Section 6 - Photoreception
	18 Biochemical Cascade of Phototransduction
		Overview
		Location and compartmentalization of rods and cones
		Dark-adapted rods
			The resting dark-adapted state
				The membrane potential
				The dark current and the cGMP-gated channel
				Ca2+ and the exchanger
				Control of [cGMP] by guanylate cyclase and PDE6
				Rhodopsin
				G-protein, Gt
				Importance of lipid milieu
			The activation phase of a light response
				Photoisomerization of rhodopsin
				G-protein activation
				PDE6 activation
				Channel closing
				Slowing of neurotransmitter release
			The recovery phase
				Rhodopsin phosphorylation, retinoid recycling and regeneration
				Arrestin binding
				cGMP restoration by guanylate cyclase activation
				G-protein and PDE6 inactivation by RGS9-1
			Amplification
			Responses to saturating light levels
			Adaptation to changing levels of ambient lighting (see Chapter 20)
			Turnover of guanine nucleotides
		Comparison of cones and rods
			Similarities and differences of phototransduction molecules
			Physiological differences
		Phototransduction and disease
			Retinal degeneration and night blindness
		What we don’t know
		Where the field is headed
		References
	19 Photoresponses of Rods and Cones
		Photovoltage response to flashes
		Photocurrent response to flashes
		Detecting single photons
		Photocurrent response to steady light
		Action spectra of rods and cones
		CNG channel and Na+/K+,Ca2+ exchanger
		Role of inner segment conductances
			Delayed rectifier potassium current, IKV
			Hyperpolarization-activated current, IH
			Voltage-activated calcium current, ICa
			Calcium-activated potassium current, IK(Ca)
			Calcium-activated anion current, ICl(Ca)
			Electrotonic coupling
		Summary
		Acknowledgment
		References
	20 Light Adaptation in Photoreceptors
		Vision from starlight to sunlight
			Light adaptation versus dark adaptation
			Purposes of light adaptation
		Performance of the photopic and scotopic divisions of the visual system
			Photopic vision: the cone system is the workhorse of vision
				The responses of cones are rapid and moderately sensitive
			Comparison of photopic and scotopic light adaptation
			Scotopic vision: the rod system provides specialization for night vision
		Light adaptation of the electrical responses of cones and rods
			Saturation of the electrical response in rods and its avoidance in cones
			Desensitization and acceleration of the photoreceptor’s electrical response
			Unaltered rising phase but accelerated recovery
			Dependence of sensitivity on background intensity: Weber’s Law
			Extremely rapid recovery of human cone photocurrent
		Molecular basis of photoreceptor light adaptation
			The phototransduction cascade
			Photoreceptor light adaptation independent of calcium
				Accelerated turnover of cGMP
			Calcium-dependent mechanisms of rapid light adaptation: re-sensitization through prevention of saturation
				Powerful negative feedback loop mediated by calcium
				Guanylyl cyclase activation
				Shortened R* lifetime
				Channel reactivation
			Molecular basis of the cone’s incredibly rapid recovery from light exposure
			Cone avoidance of saturation
			Modeling of human cone light adaptation
		Slow changes in rods: light adaptation or dark adaptation?
			Light-induced change in the dominant time constant
			Light-induced translocation of proteins
		Dark adaptation of the rods: very slow recovery from bleaching
		References
Section 7 - Visual processing in the retina
	21 The Synaptic Organization of the Retina
		Kinds of neurons
			The multipolar neuron phenotype
			The gliaform cell phenotype
			True glia and vasculature
		Basic synaptic communication
			Photoreceptor ribbon synapses: small-volume multi-target signaling
			BC ribbon synapses: semi-precise target signaling
			AC and AxC conventional fast synapses: precise presynaptic → postsynaptic signaling
			AC, AxC, and efferent slow transmitter synapses: large volume signaling
			HC non-canonical signaling
			Coupling types and coupling patterns
		Fast, focal neurochemistry, synaptic currents, and amplification
		Global neurochemistry and modulation
			Modulation by transporters
			Signal processing
			Sign-conserving (>) and sign-inverting (>i, >m) transfers
			Synaptic chains and polarity
			Feedback, feedforward, and nested feedback/feedforward
			Caveats
		Networks
			The synaptology of center-surround organization
			The synaptology of mammalian rod pathways – evolution of a new amplification scheme
			The synaptology of motion – AC surrounds from afar
			The synaptology of color – HC surrounds again?
				R/G opponency
				B/Y opponency
			Revising the retinal synaptic networks with disease
		References
	22 Signal Processing in the Outer Retina
		Electrical synapses (coupling) between photoreceptors
		Glutamatergic synapses between photoreceptors and second-order retinal neurons
		Horizontal cell responses
		Horizontal cell output synapses
		Rod and cone pathways and bipolar cell output synapses
		Bipolar cell responses and center-surround antagonistic receptive field (CSARF) organization
		Acknowledgments
		References
	23 Signal Processing in the Inner Retina
		Bipolar cells form parallel pathways and provide excitatory input to the IPL
		Synaptic mechanisms shape excitatory signals in the IPL
		Amacrine cells mediate inhibition in the IPL
		GABAergic feedback inhibition changes the timecourse of bipolar cell signaling
		GABAergic inputs to the bipolar cell axon terminals contribute to surround signaling in the retina
		The contributions of the inner and outer retina to ganglion cell receptive field surround organization
		Glycinergic inhibition plays several different roles in the IPL
		Neuromodulators in the IPL
		Parallel ganglion cell output pathways
			Ganglion cells encode color information
			Directional selective ganglion cells
			Intrinsically photosensitive ganglion cells
			Ganglion cell types form a retinal mosaic
		Conclusions
		References
	24 Electroretinogram of Human, Monkey and Mouse
		Introduction
		Generation of the ERG
			Radial current flow
				Glial currents
			Stimulus conditions
		Non-invasive recording of the ERG
		Classical definition of components of the ERG
		Slow PIII, the c-wave and other slow components of the direct current (dc)-ERG
		Full-field dark-adapted (Ganzfeld) flash ERG
			Dark-adapted a-wave
				Negative ERGs
				Modeling
				Mixed rod-cone a-wave
				Timecourse of the rod photoreceptor response
			Dark-adapted b-wave (PII)
			Scotopic threshold response (STR)
		Light-adapted, cone-driven ERGs
			Isolating cone-driven responses
			Light-adapted a-wave
			Light-adapted b-wave
			Light-adapted d-wave
			Flicker ERG
			Oscillatory potentials
			Photopic negative response
			Pattern ERG
		Multifocal ERG
		Closing comments
		References
Section 8 - Non-perceptive vision
	25 Regulation of Light through the Pupil
		The neuronal pathway of the pupil light reflex and near pupil response
			Afferent arm of the pupil light reflex
			The interneuron arm of the pupil light reflex
			The efferent arm of the pupil light reflex
			The pupil near reflex and accommodation
			Pupil reflex dilation: central and peripheral nervous system integration
			Other neuronal input to the iris
		Structure of the iris
			Iris sphincter, iris dilator, and iris color
		Properties of light and their effect on pupil movement
		Relative afferent pupillary defects
			Clinical observation of the pupil light reflex
			Computerized pupillometry
			Pupil perimetry
		Efferent pupillary defects
			Anisocoria
			Pupil inequality that increases in the dark
			Pharmacologic diagnosis of Horner syndrome with cocaine or apraclonidine
			Pharmacologic localization of the denervation in Horner syndrome
			Congenital and childhood Horner syndrome
			Pupil inequality that is increased in bright light
			Examination of the iris with high magnification using the slit-lamp biomicroscope
			Pharmacologic response of the iris sphincter to cholinergic drugs
				Cholinergic supersensitivity
				Subsensitivity of the iris sphincter to cholinergic testing
			Adie’s tonic pupil: postganglionic parasympathetic denervation
			Pupil involvement in third nerve palsy
			Aberrant regeneration in the third nerve
			Light-near dissociation: evaluation of the near response
			When the pupil fails to dilate
		References
	26 Ganglion-Cell Photoreceptors and Non-Image-Forming Vision
		Overview
		Historical roots
		Discovery of melanopsin and ganglion-cell photoreceptors
		Distinctive functional properties of ipRGCs
			Melanopsin chromophore and pigment bistability
			Spectral tuning
			Invertebrate-like phototransduction cascade
			Depolarizing photoresponse with action potentials
			Sensitivity
			Kinetics
			Morphology, retinal distribution and receptive field
			Resistance to pathological states
		Synaptic input
			Bipolar cell input
			Amacrine cell input
			Color coding of synaptic inputs
		Synaptic output and physiological functions
			Intraretinal output
			Central projections
				The pupillary light reflex
				Circadian photoentrainment and photic modulation of the pineal
				Acute regulation of activity and sleep
				Lateral geniculate nucleus and conscious light perception
		Development
		References
Section 9 - Visual processing in the brain
	27 Overview of the Central Visual Pathways
		Targets of the retinal projections
		Visual field lesions
		References
	28 Optic Nerve
		Introduction
		Optic nerve anatomy
			Retinal ganglion cell axons within the nerve fiber layer
			Intrascleral optic nerve
			Intraorbital optic nerve
			The optic canal
			Intracranial optic nerve and the optic chiasm
			The optic tract and lateral geniculate nucleus
		Optic nerve axon counts and dimensions
		Microscopic anatomy and cytology
			Axons
			Oligodendrocytes and myelin
			Astrocytes
			Microglia
			Meninges and meningothelial cells
		Blood supply
			Optic nerve head
			Intraorbital optic nerve and optic canal
			Intracranial optic nerve, chiasm, and optic tract
			Vascular biology
		Optic nerve development
			Generation of optic nerve oligodendrocytes and myelination
			Generation of optic nerve astrocytes
			Development of optic nerve meninges
			Axon number
			Axon growth
			Axon guidance
		Optic nerve physiology
			Retinal ganglion cell electrophysiology and synaptic transmission
			Axonal conduction
				Action potentials
				Role of oligodendrocytes and myelin
				Role of astrocytes
			Axonal transport
		Optic nerve injury
			Clinical implications
			Types of optic nerve injury
				Traumatic optic neuropathy
				Ischemic optic neuropathy
				Optic neuritis and inflammation
				Compressive optic neuropathy
				Glaucoma
				Papilledema
			Retinal ganglion cell death after optic nerve injury
				Time course
				Apoptosis
				Signaling of axonal injury
			Phagocytosis and immune activation
			Gliosis
			Failure of axon regeneration
				Glial inhibition of neurite extension
				Neuron-intrinsic limitations to axon regeneration
		Optic nerve repair
			Optic nerve remyelination
			Neuroprotection and retinal ganglion cell survival
			Regeneration of RGC axons
			“Neuroenhancement” of retinal ganglion cell function
		Conclusions
		Acknowledgments
		References
	29 Processing in the Lateral Geniculate Nucleus (LGN)
		The lateral geniculate nucleus: the gateway to conscious visual perception
		Overview of lateral geniculate anatomy
			Layers and maps
			Cell classes
			Inputs: the retina
			Inputs: extraretinal sources and cortical feedback
			Outputs: projections to V1 and beyond
		LGN circuits: How are visual signals regulated?
			Feedback and feedforward pathways
			Circuit neurochemistry
		Signal processing in the LGN
			Receptive field properties and parallel processing
			Physiology of M, P, and K cells
			The influence of the “extra-classical” surround
			The impact of feedback
		The LGN and arousal, attention and conscious vision
		The LGN and motor planning
		The LGN and binocular rivalry and visual awareness
		Conclusions
		References
	30 Processing in the Primary Visual Cortex
		Overview: The primary visual cortex constructs local image features
		Overview of cortical organization: a general road map
		Layers, connections, and cells of V1: The inputs, outputs, and general wiring
			LGN inputs
			Other inputs to V1
			Cell classes and connections within V1
			Output pathways from V1
		Receptive field properties: How is V1 different from the LGN?
		Columns and modules: Outlining the functional architecture of V1
		How do parallel inputs relate to parallel outputs?
		Does V1 Do More?
			The importance of time
			The importance of context
		Conclusion
		References
	31 Extrastriate Visual Cortex
		What is extrastriate visual cortex?
		Methods used to identify extrastriate areas in monkeys and humans
			Histology
			Retinotopic mapping
			Connection patterns
			Functional specificity
			Comparing visual areas in monkeys and humans
		Processing streams in extrastriate cortex
		V2
		Areas of the dorsal stream
			MT/V5 and related areas
			V3
			V3A
			PO/V6
			Parietal lobe areas
		Areas of the ventral stream
			V4
			Inferotemporal cortex
				PIT/TEO
				TE
		References
Section 10 - Visual perception
	32 Early Processing of Spatial Form
		Introduction
		Foveal window of visibility
			What limits our contrast sensitivity?
			What is the relationship between the contrast sensitivity function and the response of single cortical cells?
			The contribution of M & P pathways to contrast sensitivity
				Do these two parallel systems carry the same or different contrast sensitivity information?
			The contribution of different cortical areas to contrast sensitivity
			The effect of disease on contrast sensitivity
		Peripheral window of visibility
			Is the periphery specialized for detecting anything?
			Why does contrast sensitivity for high spatial frequencies decline with eccentricity?
		Luminance
		Chromatic sensitivity
		Suprathreshold sensitivity
		Conclusion
		Acknowledgments
		References
	33 Visual Acuity
		Defining and specifying visual acuity
			Minimum visible acuity
			Minimum resolvable acuity
			Minimum recognizable acuity
			Minimum discriminable acuity
		Limiting factors in visual acuity
			Optical quality of the eye
				What limits optical image formation of the eye?
				Refractive error and defocus results in a marked loss of image quality
			Photoreceptor size and spacing; aperture size; the “Nyquist” limit; aliasing
			Cone to ganglion cell convergence
			Eccentricity
			Crowding in peripheral vision
			Luminance
			Contrast
			Time
			Motion
			Anisotropies
			Visual acuity and reading
		Spatial vision with low contrast
			The contrast sensitivity function represents our window of visibility
			The CSF in peripheral vision
			Clinical testing of visual acuity
				Visual acuity chart design considerations
			Clinical tests for CSF
			Glare
			Development of spatial vision
				Development of visual acuity and CSF
				Development of hyperacuity
			Visual acuity through the lifespan
			Amblyopia
				Crowding and amblyopia
		References
	34 Color Vision
		Molecular genetics of color vision and color deficiencies
		Tests of color vision
		Color appearance
			Blue-yellow circuitry
			Red-green circuitry
			Black-white circuitry
		Future directions
		References
	35 The Visual Field
		Introduction
		The psychophysical basis for perimetry
		The physiologic basis for perimetry
		Types of perimetric testing
			Kinetic perimetry
			Static perimetry
			Suprathreshold static perimetry
		Detection of perimetric sensitivity loss and interpretation of results
		Patterns of visual field loss associated with different pathologic conditions
		Determination of visual field progression
		A guide for interpretation of visual field information
		New perimetric test procedures
			Short wavelength automated perimetry (SWAP)
			Frequency doubling technology (FDT) perimetry
			Flicker and temporal modulation perimetry
			Motion perimetry
			High pass resolution perimetry
			Rarebit perimetry
			Multifocal visual evoked potentials (mfVEP)
		Conclusions
		References
	36 Binocular Vision
		Introduction
		Two eyes are better than one
		Visual direction
		Normal retinal correspondence
		Abnormal retinal correspondence
		Binocular (retinal) disparity
		Stereopsis
			Quantitative and qualitative stereopsis
		Stereoacuity
			Stereoacuity with refractive defocus
		Spatial frequency and contrast effects on stereopsis
		Spatial distortions from aniseikonia
		Motion-in-depth
		Suppression in normal binocular vision
		Summary
		References
	37 Temporal Properties of Vision
		Temporal summation and the critical duration
			Factors affecting the critical duration
		Temporal sensitivity to periodic stimuli
			Critical flicker fusion frequency
				Effect of stimulus luminance on CFF
				Effect of stimulus chromaticity on CFF
				Effect of eccentricity on CFF
				Effect of stimulus size on CFF: the Granit–Harper law
				Temporal contrast sensitivity
				Chromatic temporal sensitivity
				Spatial effects on temporal sensitivity
				Mechanisms underlying temporal sensitivity
				Surround effects on temporal sensitivity
				Differences between mean-modulated and luminance-pedestal flicker
				The effects of flicker on perception
				Temporal phase segmentation
				Clinical applications of temporal sensitivity measurements
		Motion processing
			Psychophysical and perceptual evidence for unique motion processing
			The neural encoding of motion
			Clinical applications of motion processing
		References
Section 11 - Development and deprivation of vision
	38 Development of Vision in Infancy
		Methodologies for assessing infant vision and their interpretation
			Preferential looking
			Visual evoked potentials
			Ocular following movements
			Hierarchy of visual processing
			Spatio-temporal vision
			Temporal resolution
			Grating acuity
			Vernier acuity
			Optotype acuity
		Motion
			Motion direction asymmetries
		Binocular vision
			Fusion
			Stereopsis and disparity sensitivity
				Age of onset of disparity sensitivity
				Development of disparity sensitivity
		Summary
		References
	39 Development of Retinogeniculate Projections
		Retinogeniculate projections are refined during development
		Activity-dependent refinement of retinogeniculate projections
			What parameters of activity drive refinement?
			Synaptic inputs change strength with segregation
			Molecular mechanisms involved in activity-dependent axonal segregation
			Molecular mechanisms guiding the formation of eye-specific axonal territories
		Summary
		Acknowledgments
		References
	40 Developmental Visual Deprivation
		Effects of early monocular form deprivation
			Constant monocular form deprivation
				Perceptual deficits
				Neural changes
			Intermittent monocular deprivation
				Alternating monocular deprivation
				Reverse occlusion
				Brief unrestricted vision during monocular deprivation
			Critical period
				Critical period for monocular form deprivation
			Molecular mechanisms of ocular dominance plasticity
		Effects of early monocular defocus
			Constant monocular defocus
				Perceptual deficits
				Neural changes
			Alternating defocus
		Effects of early strabismus
			Perceptual deficits
			Animal models of strabismus
			Neural changes
			Effects of onset age and duration of strabismus
				Onset age
				Duration
			Eye movement anomalies
		Amblyopia
			Perceptual deficits
			Neural changes
			Improved visual performance in adult subjects with developmental disorders
		Summary
		References
	41 The Effects of Visual Deprivation After Infancy
		Introduction
		The neuronal effects of visual deprivation
			Cross-modal processing in visually normal development
			Cross-modal processing in visually normal adults
			Cross-modal processing in early blind individuals
				Tactile performance
				Braille tactile processing
				Non-Braille tactile processing
				Auditory processing
				Auditory localization
				Auditory language
			Cross-modal connectivity within occipital cortex of early blind individuals
			Neuronal structure within occipital cortex of early blind individuals
				Differences in cross-modal processing between the periphery and the fovea
			Blindfolding studies
		Restoration of vision
		Concluding remarks
		Acknowledgments
		References
Index
	A
	B
	C
	D
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	H
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	J
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	M
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	Q
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