Physiological Aspects Of Vision

Med. 6573, Nervous System Spring Semester 20086 Medical School Duluth Dr. Edward K. Stauffer Physiological Aspects of Vision

March 048, 20085; 098:00-10:50 AA.M.

Reference: Nolte, 2002. The Human Brain, Chapter 17 Stauffer, 2008. Handout: Physiological Aspects of Vision

I. Introduction

The function of the visual system is to generate a perceptual image of the external environment and, thereby, allow an animal to move about in three-dimensional space without crashing into or stumbling over various barriers that might be encountered. In addition, vision enables animals to seek and/or find various objects according to the nuances of their so-called initiative or appetitive behavior.

A convenient way to approach a study of the visual system is divide it into three areas of discussion: (1) the eye as an optical instrument; (2) the physiology of the retina; and (3) the physiology of the visual pathways and the visual cortex.

A. The eye functions, in part, to condition the light rays so that they reach the back of the eyeball in an optimal configuration to interact with the light-sensitive photoreceptors at the retina.

B. The function of the retina is to transduce the light energy radiating from the optical image into neural impulses. The retina also performs a certain amount of integration (processing) of these neural signals prior to their transmission to the visual cortex.

C. At the visual and association cortex, afferent information from both retinas is further integrated (at a much more complex and sophisticated level) into a mental sensation/perception that reproduces the object being looked at.

II. Visual Optics

A. Brief review of anatomy. Students should know those structures shown in Fig. 1 and be familiar with the general structure of the retina (Fig. 2). Note the pathway of the light rays and, in particular, the sequence of retinal structures that light passes through before it impinges upon the photoreceptor elements, the rods and cones (Fig. 2). It is interesting to note that light must pass through a multitude of structures, cellular layers and processes before actually impinging on the photoreceptive elements.

B. Protective mechanisms

1. Eyelids: close over the cornea to prevent foreign objects and intensely bright light from entering the eye.

2 a. Blink reflex: stimulus (touch) is transduced at cornea, conveyed to brain via cranial nerve V and back to the musculature of the eyelids. Dazzle (bright light) and menace (rapidly approaching object) reflexes are more complex variants of the blink reflex; both are initiated by the light or visual image falling on the retina.

b. Sleep: tonic contraction of orbicularis oculi (= skeletal muscle innervated by N. VII); prevents dehydration of cornea during sleep.

c. Spontaneous blinking: sweeps the cornea and spreads lacrimal fluid.

d. Voluntary:

2. Eyelashes: entrapment of airborne particles; when activated, sensory receptors at base will discharge to initiate a blink reflex.

3. Lacrimal glands: produce lacrimal fluid (tears); lubrication for lid movement; wash away noxious agents; contains an antibacterial lysozyme to disrupt bacteria and other material; most fluid is lost via evaporation, but also via internal nasolacrimal duct when tearing is excessive (as in crying).

C. Optic media: Light transmission. Light entering the eye passes through several structures and substances before striking the photoreceptors of the retina. Some of these structures play significant roles in accommodation (focusing) (see more below).

1. Cornea: ~11 mm in diameter, ~0.65 mm thick at circumferential edge and ~0.5 mm thick

at center; no blood vessels, hence O2 and CO2 diffuses to/from surrounding tissues/fluids and/or air; minimal immunologic reactions (hence corneal transplants are facilitated if transparency is compromised). Transparency is a function of its uniform structure, avascularity and deturgescence (relative dehydration), intraocular pressure, tonicity of surrounding fluids, temperature, and improper contacts. The cornea transmits radiation in the wavelength range of 300-2000 nm (compare to visual spectrum which is only 400-700 nm). Cornea has a rich afferent innervation by nerve V (free nerve endings in the Group III & IV afferent classification).

2. Aqueous humor: similar to protein-free plasma; found in anterior and posterior chambers; volume = ~125 µl; secreted by the ciliary body and circulates (thermal convection + hydrostatic pressure) over the lens and through the pupil into the anterior chamber where it is flows into the venous drainage via trabeculae and the canal of Schlemm; intraocular pressure is the hydrostatic pressure of this humor (normal = ~20 mm Hg above atmospheric). Glaucoma, a disease of the eye, results from an increased intraocular pressure. Glaucoma leads to a loss of vision: (1) pressure effects on the cornea (= decreased transparency, usually from edema, the situation being diagnosed when the patient reports a “halo effect” when looking at a bright, point-source of light [e.g., a light bulb, not a fluorescent tube]); (2) pressure damage to the retina; (3) pressure effects on nervous tissue; and (4) pressure on the arterial supply thereby compromising nutrition.

3 Glaucoma can arise from several causes, but two are noteworthy (www.aafp.org/afp/20030501/1937.pdf):

a. Open-angle glaucoma. Fluid is secreted excessively (over-production) by ciliary body, but has free access to the trabecular meshwork; aka chronic, compensated, or simple).

b. Closed-angle glaucoma. Iris may fold into area of trabeculae or make contact with the cornea thereby blocking drainage of fluid into the trabecular meshwork and canal of Schlemm.

c. If the pressure in the eye becomes excessive, altering circulation to the retina, permanent blindness can result.1 Note, also, that nervous tissue is very sensitive to pressure so that neural conduction may be compromised even at pressure levels that do not completely occlude blood flow. The latter situation, therefore, can alter function at the retinal level and/or at the optic nerve.

3. Lens: The lens is a highly specialized structure whose primary physiological function is refraction of light. The lens (which is completely devoid of blood vessels, pain fibers or nerves) gets its nourishment from the surrounding aqueous fluid. Other characteristics include: elastic in nature with convex anterior and posterior surfaces (but curvatures are

unequal); ~4 mm thick, ~9 mm diameter; ~65% H2O, ~35% protein; suspended from the ciliary body/muscle by “zonule of Zinn” fibers; malleable (allows shape change), a property which is reduced with increased age (=presbyopia, blurred vision due to reduction in accommodative power of the lens because of reduced malleability); cataracts---i.e., opaque lens (= blurred vision without pain) caused by physical trauma, radiation, chemical factors (e.g., high glucose concentration in aqueous humor of diabetic patients), and age.

4. Vitreous (“resembling glass”) humor: gel-like material that occupies the major portion of

the eye; ~2/3rds by weight and volume of the eyeball; ~99% H2O (remaining 1% is a loose syncytium of sub-microscopic collagen strands and hyaluronic acid, which functions to maintain fluidity of the vitreous).

D. Image formation: Focusing. For efficient excitation of the retinal photoreceptors, an image of the object must be focused precisely on the retina. If not, the light rays do not converge to points and visual acuity is lost. Refraction is the mechanism of focusing.

1. Refraction. When a light wave hits a boundary between two substances (e.g., the corneal boundary between the air and the eye), the light rays are bent and travel in a new direction. The amount of bending (refraction) depends on the topography of the interfacial boundary (i.e., the curvature) and the indices of refraction of the respective substances.

1 Note that increases of pressure will be transmitted equally throughout the structure of the eye. Problems originating in the anterior chamber can have deleterious effects at the retinal level.

4 a. The refractive power of a lens is measured in diopters (D; sometimes lower case, d):

Diopter (D) = 1/(focal length in meters)

Thus, a lens with a focal length of 20 mm will have diopteric strength of 50 D (i.e., 1/0.02 m = 50)

b. Convex lenses cause parallel light rays to converge to a point. Their refractive power is measured in positive (+) diopters.

c. Concave lenses cause parallel light rays to diverge. Their refractive power is measured in negative (-) diopters.

2. Refraction by the eye. The lens and the cornea are the primary optical surfaces that focus the image of the object on the retina. The shape of both, as well as the length of the eyeball, determines the point where the light rays converge on the retina.

a. The refractive power of the cornea is greater than that of the lens because light rays are bent more in passing from air into the cornea than in passing from the aqueous humor of the anterior chamber into the lens.

i. The corneal surface is curved such that light rays from a light source hit it at different angles and are bent by differing amounts. In contrast, after leaving the lens, all rays are directed to a point.

ii. When the object has more than one dimension, the image on the retina is upside down with respect to the original light source, and is also reversed left to right.

b. Focusing power: anterior cornea ~ +48 D posterior cornea ~ -4 D lens +15 to +29 D total refractive power +59 to +73 D

c. Whereas the cornea provides most of the refractive power for focusing on the retina, the lens provides for most adjustments for changes in distance. It does this by changing its shape (= accommodation). When looking at objects in the distance (e.g., ship on the horizon of Lake Superior or watching an airplane high in the sky), the lens is relatively flat. When looking at objects at ~9 meters or closer, the lens begins to increase it accommodative strength (diopteric strength) by increasing its curvature (i.e., “rounding up”).

i. The shape of the lens is controlled by the ciliary muscle (a smooth muscle innervated by the parasympathetic division of the autonomic nervous system). The lens flattens (ciliary relaxation) when distant objects are focused upon; it becomes more spherical (ciliary contraction) to provide greater refraction when looking at near objects.

5 ii. Cells are added to the outer surface of the lens throughout life. Cells at the center are the oldest and are located farthest from the nutrient fluids that bathe the lens exterior. They age and die first, making the lens less malleable and less capable of accommodation.

iii. Decrease of refractive power of lens (reduced elasticity) with age until it is almost non-accommodating is called presbyopia (corrected with convex lenses) (Fig. 3).

iv. Cells of the lens can become opaque (and thereby impair visual acuity), forming a cataract (defective lens can be removed and vision restored to some degree by prescribing compensating lenses).

v. Accommodative mechanism. The ciliary smooth muscles are arranged around the interior surface of the eyeball in such a manner that when they contract, they pull the choroid of the eyeball forward, towards the lens (think of a sphincter muscle that does not close completely). In effect, this action “unloads” the tension in the suspensory ligaments (zonule of Zinn) such that the lens “rounds up” because of its own inherent elasticity---it becomes more convex. The degree of contraction varies with the degree of visual blurring on the retina. The amount of blurring and compensatory accommodation is processed and regulated by the cortical areas of the visual system. Accommodation begins when looking at objects located at 9 meters (approximately!) and closer. Both eyes normally accommodate together. d. Refractive errors (ametropia) (Fig. 4).

6 i. Visual defects occur when the lens or cornea do not have a smooth spherical surface. ii. The refractive apparatus of the eyeball normally (emmetropic) focuses sharp images on the retina (Fig. 4, first diagram) .

(1) Myopia (Fig. 4, second diagram). Defects in vision occur if the eyeball is too long (length of eyeball = eyeball axial length) in relation to the lens’ focal power (= axial myopia) or if the diopteric strength of the eye’s refractive apparatus is abnormally strong (= refractive myopia). As a result, images of objects are focused in front of the retina. Thus, in myopia, eyeball axial length (AL) is greater than the focal length (FL) of the eye’s refractive apparatus (i.e., AL>FL). As a result, parallel light rays are focused in front of the retina resulting in nearsightedness or myopia (cannot see distant objects clearly). This condition is corrected by concave lenses (Fig. 1B, third diagram). The near point is defined as the closest distance to the eye at which an object can be brought into focus by maximum accommodation/ciliary contraction (normal eye: ~10 cm). The accommodative power of the eye decreases with age, a condition known as presbyopia (Fig. 3; see above). Both of these phenomena contribute to the familiar behavior of people holding objects further and further away from the eyes in order to accurately visualize the details of the object being looked at (e.g., when trying to read a book).

7 (2) Hyperopia (aka hypermetropia) (Fig. 4, fourth diagram). If the eyeball is too short for the lens’ focal power or if the diopteric strength of the eye’s refractive apparatus is abnormally weak, light rays would be focused behind the retina resulting in farsightedness. AL

(3) Astigmatism (Fig. 4, bottom diagram). If the curvature of the cornea (or lens) is not equal on all meridians, light rays will be refracted unequally and the image on the retina will be out of focus depending on which meridian they are passing through.2 This condition is called astigmatism. It is corrected by lenses, which have cylindrical characteristics (think of light passing through a solid glass stirring rod; rather than the light being focused at a point, the light would be focused along a line). Astigmatism is diagnosed and characterized by an axis and strength of abnormality. Note in Fig. 4 (bottom illustration) that the horizontal line (bold) is in focus at the retina, whereas the vertical line (dashed) would be in focus behind the retina.

(4) Ophthalmoscope. Instrument designed to allow an observer to examine another person’s retina and eye with clarity. It must emit a relatively strong beam of light and at the same time correct for any refractive errors of both the subject’s and the examiner’s eye. The adjustable lenses of the ophthalmoscope allow for this correction.

(5) Retinoscope. Instrument used to assess refractive errors in patients/subjects who cannot converse clearly with the examiner (e.g., small child). Its use is based on determining where the first appearance of retinal glow occurs with respect to the direction of light movement as the light is moved across the pupil.

(a) Emmetropic eye: Red glow suddenly appears and fills the entire pupil.

(b) Myopic eye: Red glow first appears on the side of the pupil which is contralateral (myopic = opposite) to the direction of light movement (e.g., light moving from left to right = glow appears first on the right side).

(c) Hyperopic (hypermetropic) eye: Red glow first appears on the side of the pupil which is ipsilateral to the direction of light movement (e.g., light moving from left to right = glow appears first on the left side).

2. Light (Intensity) Regulation: Aperture control. The iris controls the amount of light entering the eye by means of its ringlike sphincter and dilator pupillae

2 Think of a contact lens shaped like the shell of an egg. The curvatures along the respective axes are unequal. As a consequence, light rays passing through the different curvatures would be focused at different places with respect to the lens’ origin.

8 muscles. In addition, it contains connective tissue and pigmented cells, which give it its color.

a. The sphincter pupillae contracts in response to activity in the parasympathetic fibers of nerve III. These smooth muscle fibers are arranged concentrically around the pupil. Constriction of the pupil is called miosis.

b. The dilator pupillae contracts in response to activity in thoracic sympathetic fibers. These smooth muscle fibers are arranged radially around the pupil. Dilation of the pupil is called mydriasis.

3. Position (Gaze) Control: Oculomotor movements. The function of the oculomotor system is to control the orientation of the two eyes so that the optical image is aligned with and falls on the fovea. The receptor anatomy and functional organization of the fovea is optimal for visual resolution in space and time. Many oculomotor movements are volitional according to the wishes of the observer; some are purely reflex in nature (e.g., nystagmus). The extraocular muscles (EOMs) are striated, skeletal muscles. However, the EOMs contain a mixture of tonic (non- twitch slow, similar to those found in the muscle spindle) and phasic (fast twitch) fibers. The tonic muscle fibers have certain unique characteristics, which allow them to contract repetitively without undue fatigue.

a. The oculomotor system regulates these movements. It is composed of several central regions and pathways, and the “lower” motor neurons of cranial nerves III, IV, and VI that innervate the extraocular muscles. One way to remember:

“LR6SO4” (like sulfuric acid, “H2SO4”; i.e., lateral rectus via nerve VI, superior oblique via nerve IV; by default, all others via nerve III)

i. Each set of muscles (medial and lateral recti, superior and inferior recti, and the superior and inferior oblique) is reciprocally innervated so that the contraction of one muscle of each pair is synergistically synchronized with the relaxation of the other muscle. In addition, each muscle contains both twitch- and tonic-types of skeletal muscle fibers. This division allows for rapid, short-lasting movements and slower, long-lasting movements.

ii. The oculomotor system can be categorized into four functional subdivisions (but which act collectively to confer the broad range of eye movements):

(1) The saccadic system (rapid searching for visual targets as in reading, scanning a picture or rapid surveillance of a scene). The movement is usually a relatively small, rapid jerk called a saccade. Saccades search the visual field, move the visual image rapidly over the photoreceptors and prevent receptor adaptation. Saccades are the fastest movements in the body (600 to 900 degrees of arc per second). Amplitude varies from a few minutes of arc to several degrees of arc. Duration of saccade equals 10-80 ms, with periods of fixation ~150-300 ms. It is interesting

9 to note that the visual image is suppressed by the brain during the actual movement so one is completely unaware of the movements from fixation to fixation. Saccades can occur during sleep with the eyes closed (rapid eye movement [REM] sleep).

(2) The pursuit system (tracking on moving objects). Smooth, continuous movements allow the eye to follow objects in the visual environment. The eye must follow a moving object in the visual field to produce this type of movement, otherwise the movement control system resorts to saccades. Pursuits require continual feedback of visual information about the moving object. Pursuit movements keep a moving visual object centered on the fovea. Velocity of moving object must be < 120 degrees/sec.

(3) The vestibular system (compensation for head movements). If a stationary visual object is focused on the fovea and the head is moved, the eyes must be moved an equal distance for the object to remain focused on the fovea (i.e., if the head moves down, the eyes must move up). The vestibuloocular system (VOS) includes the vestibular apparatus, the rostral vestibular nuclei and the oculomotor nuclei. These connections are concerned mostly with adjustments to head movements detected by the semicircular canals. Many of the movements regulated by the VOS are reflexive in nature (only three neurons from sensory receptor to efferent motoneuron [1. sensory hair cell in vestibular apparatus ---> 2. interneuron in rostral vestibular nucleus ---> 3. motoneuron in abducens or oculomotor nucleus]), and are referred to as vestibuloocular reflexes (VOR). VORs movements are faster than pursuit movements, and are neurally organized in a distinctly different manner than pursuits. Vestibular nystagmus is a pronounced statokinetic (during movement) VOR in which the eyes exhibit alternating rapid and slow flicking movements with the fast (saccade) and slow (pursuit) components of the movement occurring in the opposite direction.

When the head is tilted to one side, the eyes will make small compensatory rotatory movements in the coronal plane in an attempt to maintain the visual images in the same orientation on the retina. The spatial extent of these rotational movements are restricted by the oculomotor muscle attachments.

(4) The vergence system. Used to track a visual object by turning the eyes inward as the object gets closer (convergent) and outward as it moves away (divergent).

(5) Other definitions: Conjugate eye movements = both eyes move together in the same direction with respect to head coordinates (e.g.

10 furtive, sideways glance at some attractive person while walking in the halls of UMD [or elsewhere]); saccades and pursuits are conjugate movements. Disjunctive eye movements = eyes move together in mirror-image directions with respect to head position (e.g., convergence or eyes crossing, and divergence or eyes uncrossing).

b. Depth perception. The precise and accurate means for localizing objects in space utilizes the images seen simultaneously by both eyes, defined as stereopsis (stereoscopic vision).

i. Based on the fact that the visual cortex on one side receives input from the contralateral nasal hemiretina and the ipsilateral temporal hemiretina, and the presence of an inter-hemispheric link through the corpus callosum. Right eye “sees” more of the right visual field; left sees more of the left.

ii. The basis for stereopsis is the horizontal disparity between the two hemiretinal images (retinal image disparity). The horizontal disparities between the two hemiretinas viewing the same visual field obtain the cues of depth and, in turn, the processing in the neurons of the visual pathways lead to depth perception.

iii. Relative size of objects also contributes to depth perception: Larger objects perceived as closer than smaller objects.

iv. Moving parallax: Objects closer to subject move faster than those further away.

III. Retinal Physiology

A. Duplicity Theory. This theory postulates that cones function at the high light intensities of daylight vision, conferring advantages of high visual acuity and color vision, while the rods have the greater sensitivity required for night vision but do not mediate color and cannot resolve fine details.3 The theory applies better to the rod and cone neural systems together, rather than to the rods and cones alone. This is because some of the functional differences are not due entirely to differences between rods and cones themselves, but result partly from processing (neural integration) in the rod and cone afferent pathways and neural centers.

B. The retina contains the photoreceptor cells (named rods and cones because of their structural appearance). Only the rods and cones respond directly to light; all other cellular elements of the retinal pathways are influenced only by synaptic input arising from other neurons. Each retina contains ~120 million rods and ~7 million cones, but only ~1 million optic nerve fibers leading from it. Thus, there is a substantial amount of synaptic convergence between

3 Alternatively, the theory states that actions, which require high visual acuity and/or color discrimination, must be performed under conditions of relatively high light intensity. If light conditions are relatively low, one cannot perform such actions.

11 the photoreceptors and the ganglion cells (axons of the latter cells form the optic nerve leading to the lateral geniculate body). Note also that there are several other types of cells in the retina and these provide the substrate for a significant amount of integration of signals before transmission to the cortical centers (cf. Fig. 2).

1. Both cell types contain light-sensitive molecules called photopigments whose function is to absorb light (Figs. 5-7 below). Light energy causes the respective photopigments (rod photopigment = rhodopsin; cone photopigments = erythrolabe, chlorolabe, and cyanolabe; see more below) to change their molecular configuration into an activated intermediate (Fig. 5; for rods, the activated form is metarhodopsin II (= Rh* in Fig. 7A)). The activated intermediate then triggers a second messenger cascade ultimately leading to changes of the photoreceptor’s membrane potential (Fig. 6 & 7). Unlike the majority of other sensory receptors, the outer-segment membranes of the photoreceptors decrease their permeability to cations (Na+ and Ca2+ ions when stimulated (Fig. 6 & 7). The “stimulus-gated” channels close during the transduction event thereby hyperpolarizing the receptor cell membrane (Fig. 6B & 7C). In the dark, the photoreceptors are depolarized (by the open cation

12 channels, Fig. 6A & 7C) thereby releasing a tonic level of the an inhibitory neurotransmitter, in this particular case, glutamate.4 When light strikes the receptor, the cell is hyperpolarized, neurotransmitter release is decreased and the postsynaptic bipolar (or horizontal) cell is excited (i.e., removal of inhibition = excitation). Thus, the hyperpolarized receptor potential is converted into excitation.

4 In the nervous system, glutamate is generally excitatory, but in this case it is inhibitory. Recall that a neurotransmitter’s action depends on the properties of the receptor to which it attaches (cf. Suryanarayanan & Slaughter, 2006. J. Neurosci. 26(6): 1759-1766).

13 14 2. Four kinds of photopigments

a. Rhodopsin (rod photopigment) is very sensitive to light. In humans, the maximum scotopic (= dark-adapted) sensitivity is at a wavelength of ~500 nm. Rods provide a visual image composed primarily of grey tones.

b. Erythrolabe, chlorolabe, and cyanolabe are found in the cones5 and are sensitive to light wavelengths of the three primary colors (red, green, and blue, respectively). Color vision is thought to arise from neural integration of information from all three types of cones; the integration occurs at the level of the visual cortex. Color blindness: genetic, sex-linked trait in which cones that respond to red, green or blue light are missing (or deficient) and the person is blind to these colors; protanopia= red insensitivity, deuteranopia=green insensitivity, tritanopia=blue insensitivity.

3. Composition of photopigments: all four photopigments are made up of a protein (opsin) bound to a chromophore molecule (11-cis-retinal). The opsins are not sensitive to light. Light sensitivity is conferred solely by the presence of 11-cis-retinal.

a. All four photopigments possess 11-cis-retinal as the chromophore, but the four different opsins confer the specific spectral sensitivities on the photopigments whether to red (@ ~558 nm), green (@ ~525 nm), or blue (@ ~440 nm).

b. Light acts on the photopigments to isomerize 11-cis-retinal to the all-trans-retinal configuration (Fig. 5). The initial step of this isomerization takes place within a few picoseconds (10-12 sec) and is followed by a spontaneous sequence of reactions (involving several intermediates) to form photoexcited rhodopsin (Rh* = metarhodopsin II).

i. After the breakdown of the photopigment in the presence of light (the “light” reaction = rhodopsin ---> prelumirhodopsin), the photopigment molecule undergoes a series of “dark” reactions in which the chromophore dissociates from the opsin, is rearranged and eventually rejoined to opsin to replenish the photopigment (Fig. 5). Retinal is a derivative of vitamin A. Vitamin A deficiencies can lead to night blindness (nyctalopia = decreased ability to “see” in reduced levels of illumination) because there is not enough retinal to recombine with the opsin to replenish the rod rhodopsin. If untreated, nyctalopia can lead to deterioration of rod outer segments and eventually to total blindness.

ii. Thus, the only action of light is to change the chromophore; everything else in the sequence leading to vision (chemical, physiologic, or psychological) occurs in the absence of light and is referred to as the “dark” reaction.

5 Iodopsin is the name given to a cone photopigment originally isolated from chicken retinae (cf. Wald & Clark, 1937. J. Gen. Physiol. 21: 93-105).

15 (1): light rxtn (occurs with light) = rhodopsin ---> prelumirhodopsin

(2): dark rxtn (occurs without light) = prelumirhodopsin ---> ---> ---> opsin + all-cis-retinal ---> rhodopsin. Thus, once rods have been excited, they cannot be excited a second time until they replenish their rhodopsin under dark or dimly lighted conditions.

C. The rod receptor cell contains rhodopsin (aka visual purple), which is very sensitive to and can react to very small amounts of light (rod vision = scotopic vision = dark- adapted eye, i.e., the person has been sitting in the dark for some time). The rods act as photoreceptors during conditions of poor lighting and for night vision. Rods can respond (generate a receptor potential) to a single photon---this unitary response usually does not reach consciousness.

1. The rod responses do not indicate color, show only shades of gray, and their acuity is very poor.

2. The rods are most numerous in the peripheral retina, nearest to the ciliary body, and are absent from the retinal center (the fovea). The peripheral retina exhibits a greater sensitivity to weak light because as many as 600 rods converge on to the same optic nerve fiber (convergence ratio of rods to ganglion cells = 600:1). This results in a marked summation of synaptic signals on the peripheral ganglion cell. This explains why one often “looks to the side” in order to see dim stars at night. By “looking to the side”, the starlight falls on the periphery of the retina where there are more “collectors” (i.e., rods) converging on to the ganglion cells. Once a ganglion cell discharges, a signal can be sent to the visual cortex (via the lateral geniculate body) and there can be a visual perception (“seeing a star”).

D. There are three types of cones, each type containing one of the three photopigments for color vision. Cones: (a) operate only at high levels of illumination (cone vision = photopic vision = light-adapted eye); (b) are the photoreceptors for day vision; (c) are responsible for high visual acuity; and (d) subserve color vision.

1. Cones are concentrated in the center of the retina (the fovea) where the eye focuses light rays from objects requiring vision of fine detail.

2. From the periphery to near the fovea, the population of rods decreases until only cones are present at the fovea. At the fovea, the cones converge on ganglion cells with a convergence ratio of ~1:1. Thus, there are more lines of information projecting to the ganglion cells, and the receptor mosaic has a finer grain (resulting in a more detailed visual perception). The outer segment of both rods and cones becomes more slender near the center of the retina, which, in turn, progressively increases the acuity of vision at the fovea (i.e., the receptive fields of the photoreceptor mosaic becomes smaller and smaller as one approaches the fovea).

16 E. Retinal synaptology. Receptor cells in the retina (rod or cone) synapse on a second neuron, a bipolar cell and/or a horizontal cell (cf. Fig. 2). Bipolar cells make contacts with amacrine and/or ganglion cells. Bipolar cells tend to send signals in a vertical (perpendicular to the pigment layer) direction from the receptive cell layer to the ganglion cell layer. Horizontal and amacrine cells tend to collect and/or send signals in a horizontal (parallel to the pigment layer) direction. The axons of the ganglion cells form the optic nerve, which passes out of the eye directly to the brain (lateral geniculate body). Physiologically, therefore, the retina has: (a) an “absorptive” layer (the pigment epithelium); (b) a “receptive” or “transductive” layer (the photoreceptors); (c) an “integrative” layer (the horizontal, bipolar and amacrine cells); and (d) a “transmission” layer (the ganglion cells).

1. Cones have relatively direct lines to the brain because each bipolar cell receives synaptic input from very few cones. In turn, ganglion cells receive synaptic input from only a few bipolar cells. In the fovea, therefore, where only cones exist, there is very little convergence from cones to ganglion cells. Instead, the cones are represented by about equal numbers of bipolar and ganglion cells. The number of optic nerve fibers leading from the fovea is almost equal to the number of cones located there. This results in a convergence ratio of nearly 1:1 and this, in turn, provides for precise information about the retinal areas being stimulated.

2. Conversely, many rod cells converge on bipolar and ganglion cells (from ~20:1 up to ~600:1; see above) so that both spatial and temporal summation is very high, but acuity is poor. Thus, a low-intensity light stimulus, that would only produce a subthreshold response in a cone ganglion cell, can actually generate an action potential in a rod ganglion cell. This explains why objects in a darkened room are indistinct and appear only in shades of gray.

3. As a result of dark adaptation, the sensitivity of the eye improves after being in the dark for a short time (Fig. 8). The excitability of the rod visual system depends on the number of intact rhodopsin molecules in the rods. In bright light, virtually all rhodopsin molecules have cascaded to the opsin + all-trans-retinal state (cf. Fig. 5) such that they are ineffective and vision is a function of only cone activation. When one moves from a lighted room into a darkened one, there are relatively few rhodopsin molecules available, but as the

17 rhodopsin gradually regenerates in the dark, visual sensitivity improves.6 Conversely, when one moves from a dark room to a well-lighted room, the bright light seems very intense because all of the cones (which have all of their retinal in the 11-cis form) are suddenly activated. The perception is of a very bright light, almost painful!7

F. Visual Acuity

Acuity refers to the visual system’s ability to discriminate the specific or fine details of the visual object/scene. It should be obvious that visual acuity is, in part, a function of the optics of the eye. Clearly, any condition that compromises the transparency of the optical pathway will reduce visual acuity. Visual acuity is primarily a function of the cone system, and is greatest at the fovea. Three areas of acuity can be identified:

1. Spatial Acuity: Ability to resolve two points in space. As depicted in Fig. 9, spatial acuity is a function of brightness and the type of photoreceptor being activated. Note in Fig. 9, that as the brightness of the test stimuli (test stimuli = the gap in the “C”, the Landolt C) is increased, the ability to resolve the gap’s orientation increases at the fovea. Acuity at the periphery of the retina remains relatively constant at a very low level. Thus, visual acuity is greatest at

6 Think of going into a dark theater from a bright sunny day. Essentially, the only objects that you can “see” are those being projected on the screen. Or, if an usher with a flashlight is available, s/he will shine it on the aisle floor to show you the way. Otherwise, you tend to stumble over other people or step on their feet (or spill your drink on them!). Once you have been in the theater for a few minutes, your rods begin to recover (replenish their rhodopsin) and you begin to see objects around you. 7 Sometimes, people will sneeze when moving into bright light. The basis of this reflex is unknown or, at best, poorly understood (at least by Dr. Stauffer!).

18 the fovea where only cones are located, but the level of illumination must be sufficient to excite the cones. Remember, cones confer visual acuity, but they only function when the level of light is sufficient to excite them.

Acuity is often assessed using Snellen eye charts, the familiar charts containing square letters of the alphabet. The letters vary in size such that each one subtends a visual angle of 5 minutes at a particular distance. The designation, 20/20, refers to the size of a letter that the normal population can distinguish when standing 20 feet away from the chart. A person who, when standing at 20 feet, can only distinguish the letter which the normal population can resolve at 200 feet is said to have 20/200 acuity (i.e., low acuity = nearsightedness). At the other end of the scale, a person who, when standing at 20 feet, can distinguish the letter which the normal population can resolve at 15 feet is said to have 20/15 acuity (i.e., high acuity). Checking spatial acuity with the Landolt C is preferable to the Snellen alphabet letters because people can often recognize and identify some letters better than others simply by their overall shape.

2. Temporal Acuity: Ability to distinguish visual events in time. Fig. 10 illustrates the relation between the critical fusion frequency (CFF) of a flashing light and the intensity of the flashing light. CFF is the frequency at which a repetitively flashing light appears to be continuous rather than flashing. When a low intensity light (< -2 Log stimulus intensity in Fig. 10) is aimed at the fovea (0°, solid line and open circles), the ability to distinguish the flashing light is very low (~5 Hz) because the intensity isn't high enough to excite the cones. As the intensity of light at the fovea is increased, however, the CFF increases (>50 Hz). Thus, since only cones are found at the fovea, Fig. 10 shows that cones are very good at distinguishing flashing lights, but the light must be of sufficient intensity to stimulate them. When the flashing lights are aimed at parts of the retina where both rods and cones are present (5° and 20° away from the fovea), even at low light intensities, there is some capacity to resolve

19 the repetitive lights, but the capacity is lower (CFF < 10 Hz). As the light intensity is increased on areas where both rods and cones are present (5° and 20°), then cones become activated and the CFF increases. Again, at low light intensities rod function is evident, but they not very good at distinguishing flicking lights. As the light intensity is increased, the cones are recruited into action and CFF increases.8

3. Spectral Acuity: Ability to distinguish differences in the electromagnetic spectrum. The visual system can transduce wavelengths of ca. 400 to 700 nm (blue to red) (Fig. 11). As mentioned above, the ability to resolve the colors of the spectrum is a function of the cone system. The eye’s sensitivity to a visual stimulus depends upon the wavelength of the light. If a subject must adjust a test stimulus to produce a perception of constant brightness, less intensity is

8 In the early years of motion pictures, projector speeds were relatively slow. Since the projector light was quite bright, the cones could detect “flicking” (or flashing) of the image on the screen as the film frames passed by the projector lens. In those days, going to the movies was often referred to as going to the “flicks”. The nuisance of flicking was overcome by simply increasing the projector speed (>50 Hz). Can you think of another procedure to overcome the flicking problem?

20 required at some wavelengths than at others. A plot of this relative sensitivity after dark adaptation (scotopic conditions) and light adaptation (photopic conditions) is shown in Fig. 12. These spectral sensitivity curves have been

adjusted (normalized) to the same peak sensitivity, but the peak sensitivity of the photopic curve is, in fact, three orders of magnitude less sensitive on an absolute scale (reflecting the rods’ greater sensitivity to light per se and that cones must be activated with light of greater intensity). The shift of the peak of the two respective curves is 9 called the Purkinje shift. The shift reflects predominantly rod function at low light intensities versus cone function at high light intensities. Also, cones are more sensitive to light at red wavelengths than are cones.

9 Same scientist of cardiovascular fame, Johannes E. von Purkinje (aka Jan E. Purkyne), Bohemian anatomist and physiologist (1787-1869).

21 The dashed line in Fig. 12 shows an interesting feature of the visual system. Note that red light is quite effective at exciting an eye under photopic conditions, but has virtually no effect on an eye under scotopic conditions. Red light will excite the cones of a photopic eye, but not the rods of a scotopic eye. In other words, in a room illuminated with red light only, an individual can perform actions requiring high acuity (i.e., reading, writing, etc.), but the rods will not be activated at all. Under red light, the rod photopigments will be in the 11-cis conformation because they will not 10 have been “bleached” by the light. Therefore, the rods will be perfectly capable of providing visual information if the individual suddenly needs to move into dimly lighted conditions. Thus, individuals (e.g., pilots) who are “on call” during the night can be in a red-lighted room and can perform duties normally requiring daylight intensities, but when required to immediately leave the room to perform actions in the dark (e.g., scramble into airplane cockpits), they can do so because their rods have not been bleached (i.e., into the conformation requiring the dark reaction). Therefore, pilots on an aircraft carrier at night can run from a red-lighted room out onto the dark deck, climb into their aircraft with out tripping or otherwise hurting themselves, and take off.

10 In Fig. 5, the cascade of reactions from rhodopsin to metarhodopsin III is referred to as the “bleaching” reaction. A solution of rhodopsin is dark purple. When exposed to light, the solution turns yellow, hence the term “bleaching”.

22 Study Guide

1. List the anatomical structures of the eye that light must pass through before reaching the retina.

2. Define the blink reflex; the dazzle reflex; the menace reflex.

3. List factors, which can compromise the transparency of the cornea. What part of the electromagnetic spectrum (EMS) is transmitted through the cornea? What part of the EMS do the photoreceptors respond to?

4. Define glaucoma. What physical parameter increase leads to glaucoma? What are the consequences of glaucoma?

5. Define presbyopia. What are cataracts? What factors can contribute to the development of cataracts?

6. Define refraction. How is the refractive strength of a lens determined? Define a diopter, and what is meant by positive (+) and negative (-) diopters. What is the diopteric “polarity” of a convex and a concave lens? Which structure of the refractive apparatus has the greatest diopteric strength? Which structure can change its diopteric strength? What is the mechanism of this change? What type of muscle is activated during accommodation? Which part of the peripheral nervous system is activated during accommodation?

7. What regulates the amount of light that enters the eye? What type of muscle is involved with this regulation?

8. Define ametropia, emmetropia, myopia, hypermetropia, hyperopia, and astigmatism. What type of lenses is used to correct these different errors? If you knew the magnitude of a patient’s refractive error, what strength and type of lens would you prescribe?

9. What is an ophthalmoscope used for? How does a retinoscope work?

10. Describe the oculomotor system and the various movements of the eye. What type of muscle is involved with oculomotor movements? Define nystagmus. How is the direction of nystagmus defined?

11. What phenomena are associated with depth perception?

12. Define the duplicity theory of vision.

13. Describe the sequence of events (biochemical and physiological) leading to a receptor potential in a rod photoreceptor. What ions are responsible for the receptor potential? What is the polarity of the receptor potential? What is the light reaction? Dark reaction?

23 14. List four photopigments and where they are found. Define the defects associated with colorblindness.

15. Explain spatial acuity, temporal acuity, spectral acuity and light sensitivity in terms of the duplicity theory of vision. How is spatial acuity measured? Distinguish between Isihara, Stilling and Snellen eye charts.

Sample Questions

1. Which of the following reactions absorbs a photon of light? A. Opsin + all-trans retinal ---> rhodopsin B. Metarhodopsin II ------> metarhodopsin III C. All-trans retinal ------> 11-cis retinal D. Rh* + transducin ------> activate phosphodiesterase E. 11-cis erythrolabe ------> all-trans erythrolabe

2. The refractive strength of a patient’s eye is equal to 45.45 D. The axial length of the patient’s eyeball is equal to 24 mm. You correctly conclude that this patient requires: A. convex lenses to correct the condition. B. concave lenses to correct the condition. C. cylindrical lenses to correct the condition. D. no corrective lenses. E. a diagnosis of emmetropia.

3. The refractive power of the unaccommodated lens is A. greater than B. less than C. equal to that of the normal cornea.

4. Application of acetylcholine to the ciliary muscle will: A. increase tension in the suspensory ligaments. B. decrease the refractive strength of the lens. C. increase the amount of curvature of the lens. D. decrease the size of the pupil. E. do nothing.

5. You determine that the intraocular pressure of a patient’s eye is 135 mm Hg. Your diagnosis is: A. nyctalopia. B. protanopia. C. myopia. D. ammetropia. E. glaucoma.