Neural Systems I - Exam 3 - Lecture 20: Eye: Introduction to the Retina (Chapter 23)

how light travels in the eye

- a ray of light entering the eye first strikes the transparent cornea - then it goes through the clear fluid within the anterior chamber of the eye (aqueous humor) - then it goes through the pupil of the iris, where it encounters the lens - from the lens it then passes into another clear fluid (vitreous humor) - finally, the ray strikes the retina - behind the retina is a layer of pigmented epithelium, whose black pigment absorbs light reaching it (i..e not absorbed by the photoreceptors), assuring that light is not reflected around inside the eye

reconversion of rhodopsin from trans to cis state

- a whole series of chemical reactions occur to return the retinal to the cis state, and thus restore its normally redish purple color - this reconversion must be accomplished before the rhodopsin molecule can again be used in any phototransduction - this reconversion occurs via a series of chemical reactions, one of which is mediated by an enzyme and which requires the expenditure of metabolic energy

rods vs. cones

- all "rhodopsin based" photopigments are composed of both a retinal and opsin component; this is true for the rhodopsin in rods, the photopigments in cones, and for all photopigments in all other organisms - the retinal is the same in all photopigments, but the molecular composition of the opsins is what is different among the photopigments; thus, each of the cone types, the red, blue, and green cones, each have the same retinal, but a different opsin - it is the particular opsin contained in the photoreceptor that: 1) renders the photopigment sensitive to a particular wavelength of light; 2) determines its sensitivity to light. - since each of the 3 cone types has a different opsin, each cone type is maximally sensitive to a different wavelength (color), but their absolute sensitivities are far less than the absolute sensitivity of rhodopsin

how the vertebrate eye works like a camera

- an image of an object in visual space is focused by a lens onto a light sensitive surface or retina at the back of the eye - there is a means for controlling the amount of light entering the eye by varying the diameter of aperture - the pupil at the front of the eye

retina

- composed of several layers of cells and the processes of these cells (which forms a circuit) - transduction, where one form of energy (light) is changed into another form of energy (electrical), occurs in the photoreceptors that actually lie in the innermost layer of the retina - light enters the eye through the pupil and lens and is captured by the photoreceptors (rods and cone), but it has to first travel through the axons of ganglion cells, which sit on the surface of the retina and bipolar cells before reaching the photoreceptors that are located at the back of the retina - the retina is part of the central nervous system, and its job is to transform light first into changes in the membrane potential of its photoreceptors and then into electrical signals for transmission to higher visual centers in the brain

fovea

- the place where cones are most concentrated, w/ only cones and no rods, is a small depression or pit near the center of the retina, called the fovea - human fovea is quite small - not only does the fovea only contain cones, but the cones are much thinner and different from the smaller number of cones that are found more sparsely in the periphery (outside of the fovea) - the fovea cones are long and thin and are densely packed in the fovea, which contains ~34,000 of them (in a very small region), which is why the fovea provides the highest acuity vision

rods

- designed to function in dim illumination - an elongated cell that can be divided into two portions that are connected by a very narrow stalk - on one side of the stalk is the so-called "inner segment", which contains the nucleus of the cell, mitochondria, the protein synthetic apparatus, and most of the other typical cellular organelles - located at the end of the inner segment is the area where the rod makes synaptic contacts w/ the next cells in the visual pathway (synaptic terminal); consequently, there are synaptic vesicles located in this region of the rod - on the other side of the stalk is the so-called "outer segment"; essentially a cylinder containing a stack of disks - these disks are nothing more than flattened, membrane-enclosed vesicles; embedded in the membrane of these disks is the photopigment, rhodopsin - rhodopsin is the chemical that absorbs light and initiates the sequence of events that change the membrane potential in rods; the initial steps in phototransduction occur in the disks - rhodopsin of rods are most sensitve to a wavelenght of ~500 nm, corresponding to a blue-green color

photochemistry of rhodopsin

- in rods, the visual pigment is rhodopsin; called a visual purple b/c it has a redish-purple color - rhodopsin itself has two components: a lipoprotein molecule known as opsin to which a molecule called retinal is covalently bound - retinal is the aldehyde of Vitamin A; since Vitamin A is an integral component of the photopigment, the result of a deficiency in this vitamin is a decrease in the photosensitivity of the eye commonly known as light blindness - rhodopsin absorbs light and upon the absorption of light, it changes color (the normal purple color is lost as the pigment bleaches) - what the absorption of light by rhodopsin does specifically is to induce a photoisomerization about a double bond in the retinal molecule; this photoisomerization converts 11-cis-retinal to all-trans-retinal; it changes the configuration of the retinal molecule, causing it to, in essence, "spring out" and thereby straighten - both the retinal and opsin can be thought of as molecules twisted into strange shapes that w/ the slightest touch (gain of energy) will spring out to assume a more "comfortable" shape - in the dark, the retinal fits snugly on a site in the opsin molecule; upon absorption of light, the molecule gains energy, and this causes a photoisomerization, which in turn causes a change in the shape of the retinal to the all-trans configuration, and that in turn causes a change in the shape or conformation of the opsin - it is the conformational change in opsin that results in its activation of the G protein, transducin - in essence, the retinal group "locks" the opsin into a compact conformation which is altered to a less compact form of opsin when the retinal undergoes the cis to trans isomerization induced by light - after rhodopsin has absorbed light and its retinal group has changed from the cis to trans configuration, the retinal actually separates from the opsin; when this happens, the rhodopsin molecule is "bleached," b/c its color changes from a redish purple to a light yellowish color.

vertebrate photoreceptors

- in the retina of each eye, there are ~100 M photoreceptor cells - in higher vertebrates, there are two types of photoreceptor cells: the rods and the cones - cones are the photoreceptors designed to function in bright illumination and are responsible for color vision - rods are designed to function in dim illumination

how is the hyperpolarizing receptor potential of the rods generated?

- it results from a decrease in the conductance of the membrane of the outer segment to Na+ - the resting rod membrane has a higher permeability to Na+ than that in other cell types; this continuously allows positive ions, carried by Na+, to enter the cell and accounts for the low, depolarized resting potential - when light strikes the photoreceptor, Na+ channels close and the permeability of the rod membrane to Na+ is reduced; the reduction in permeability for Na+ means that far fewer positive charges now enter the cell - photoreceptors have K+ channels in the lower segments, and thus now there is an efflux of K+ (driven by its concentration force) that shifts the membrane potential toward the K+ equilibrium potential, thereby making the interior of the cell more negative

photoreceptors hyperpolarize in response to light

- receptor potential is produced when a rod absorbs light - cones behave the same way to light as rods do - in the dark, the rod has a fairly low resting potential (~ -30 mV); when a light is shined on the rod, it hyperpolarizes!! - the response of vertebrate photoreceptors to a stimulus is not depolarizing, but rather a hyperpolarizing resonse; thus, the rod receptor potential renders action potentials less likely - rod and cones are incapable of generating an action potential

rhodopsin is highly concentrated in disks and is functional only in dim light

- rhodopsin is highly concentrated in the disk membranes; it is the most highly concentrated molecule in the body - the rod also ensures itself that any light entering the eye will be captured by at least one rhodopsin molecule - since there are many disks in each photoreceptor, you can easily see why rods are so well designed to function in very dim light - rods are ill suited for functioning in moderate or bright light - since rods are so efficient at capturing light, and since the sensitivity of rhodopsin and its amplifying effects are so strong, the rods are functioning maximally in normal light conditions - almost all of the rhodopsin is maximally bleached in normal light, and the rate at which it is reconstituted cannot keep up w/ the rate of bleaching; thus, in normal light, rods cannot respond to any change in light intensity and thus they are non-functional in normal lighting; it is the less sensitive cones that are used for vision in daylight -

cones vs rods (light sensitivity)

- rods are very sensitive; they are specialized for phototransduction under dim illumination conditions; under normal daylight illumination, the rods are almost completely adapted - cones are far less sensitive than rods; cones are specialized for phototransduction at high light intensities - daylight vision comes from cone activity; at night the illumination is usually insufficient to influence cones

what is the link b/t absorption of light and the decrease in Na+ conductance?

- the Na+ conductance decrease must occur by means of some messenger; this must be the case b/c the visual pigment is embedded in the membrane of the disks located in the outer segment - the disk membrane is separate from the membrane of the outer segment itself where the Na+ channels are located and where the conductance change actually occurs

ligand gated Na+ channels are closed through a second messenger system

- the outer segments of rods and cones have Na+ channels, but these are not voltage sensitive Na+ channels of the sort that are so common in axons - rather, these are ligand gated Na+ channels - the ligand that opens these Na+ channels is a cyclic nucleotide, cyclic guanine monophosphate (cGMP) - in the dark, there is an abundant supply of cGMP, which diffuses freely in the cytoplasm - the cGMP acts like a neurotransmitter, although in photoreceptors, it is not secreted by another cell; rather, it is a normal cytoplasmic constituent, and some of the cytoplasmic cGMP binds to the receptors of the Na+ channels, which opens their gates and thereby causes a high Na+ conductance

cones vs rods (distribution over retina)

- the roughly 5 M cones and 100 M rods in the human retina are non-uniformly distributed - the cones are concentrated in the central portions of the retina and are exceedingly rare near the edges of the retina - the place where cones are most concentrated, w/ no rods, is in a small depression or pit near the center of the retina called fovea - rods predominate at the edges of the retina - apparently, those receptors responsible for daylight vision are concentrated near the center of the back of the eye; the receptors responsible for night vision occur predominately at the periphery of the retina

blind spots (optic disks)

- there is one spot at the back of each eye where there are no photoreceptors - b/c of the "inside-out" arrangement of the retinal cell types, the ganglion cells are the cell layer closest to the vitreous humor; the axons of the ganglion cells run across the surface of the retina and converge together at the optic disk where they form the optic nerve and exit the eye - since there are no photoreceptors in the optic disk, there is actually no information going to the brain about that part of the visual space focused upon the optic disk; in effect, we are blind in a small area of each retina - we are totally unaware of this blindness; the brain tends to "fill in" an estimate of what should be in this part of the visual field by judging the visual areas surrounding this spot

the effects of light capture by rhodopsin are amplified

- through this biochemical cascade, a high degree of amplification is achieved b/ the product of each reaction is an enzyme that itself catalyzes many reactions - ex. each activated rhodopsin molecule acts like an enzyme and catalyzes many molecules of the G protein, transducin - each molecule of activated transducin activates many molecules of phosphodiesterase and each activated phosphodiesterase converts many molecules of cGMP to 5-GMP - estimated that the photoisomerization fo a single molecule of rhodopsin results in the inactivation of 100,000 cGMP molecules; incredible amplification that takes place within 1-2 seconds after the photoisomerization of a single rhodopsin molecule - the amplifying effects of the rhodopsin explain how the absorption of a single quantum in the disk membrane eventually leads to change in the Na+ conductance in the rod outer segment; thus, the visual system can respond to a single quantum of light and works virtually at is physical limits

cones

- transduce light in much the same way as rods - however, cones possess photopigments that are slightly different from rhodopsin, the photopigment in rods - in humans, there are 3 different types of cones, each containing a particular type of photopigment - all photopigments, including rhodopsin, consist of retinal plus a protein called opsin; what differs among the cone photopigments and rhodopsin is the nature of the protein opsin - each photopigment is most sensitive to a different wavelength (color) of light - one photopigment is maximally sensitive to blue (419 nm), one to green (531 nm) and one to red (559 nm); these spectral sensitivites underlie the mechanisms of color vision

how does the absorption of light by rhodopsin result in the closure of Na+ channels? there are several steps that occur once light is absorbed or captured by a molecule of rhodopsin

1. the energy in the light activates the rhodopsin in the disc membrane. 2. the capture of light by rhodopsin is similar to the binding of a ligand by a receptor coupled to a G protein. the activated rhodopsin, like a receptor binding a ligand, now activates a G protein in the disc membrane. the G protein in the photoreceptor is called transducin. 3. the activated G protein then activates a phosphodiesterase that converts cGMP into 5'-GMP, which does not bind to the Na+ channel. 4. the action of the phosphodiesterase is to cause the levels of cGMP to fall in the cytoplasm. as the concentration of cGMP falls in the cytoplasm, cGMP diffuses from the Na+ receptors. since the Na+ channels no longer have a bound ligand (cGMP), the Na+ channels close. the closing of the Na+ channels then drives the membrane potential towards the K+ equilibrium potential: it causes the membrane potential to become more negative and thus hyperpolarizes the cell from its normal resting potential. it is for this reason that the response of a photoreceptor to light is hyperpolarization.