|Neuron: Photoreceptor Cell|
Functional parts of the rods and cones which are two of the three types of photosensitive cells in the retina
A photoreceptor, or photoreceptor cell, is a specialized type of neuron (nerve cell) found in the eye's retina that is capable of phototransduction. The great biological importance of photoreceptors is that as cells they convert light (electromagnetic radiation) into the beginning of a chain of biological processes. More specifically, the photoreceptor absorbs photons from the field of view, and through a specific and complex biochemical pathway, signals this information through a change in its membrane potential.
For hundreds of years, photoreceptors in vertebrates were thought to be of only two main classes. The two classic photoreceptors are rods and cones, each contributing information used by the visual system to form a representation of the visual world, sight.
A third class of photoreceptors was discovered during the 1990s: the photosensitive ganglion cells. These cells, found in the inner retina, have dendrites and long axons projecting to the protectum (midbrain), the suprachiasmatic nucleus in the hypothalamus, and the lateral geniculate (thalamus).
There are major functional differences between the rods and cones. Cones are adapted to detect colors, and function well in bright light; rods are more sensitive, but do not detect color well, being adapted for low light. In humans there are three different types of cone - responding respectively to short (blue), medium (green) and long (yellow-red) light. The human retina contains about 120 million rod cells and 6 million cone cells. The number and ratio of rods to cones varies among species, dependent on whether an animal is primarily diurnal or nocturnal. Certain owls have a tremendous number of rods in their retinas — the eyes of the tawny owl are approximately 100 times more sensitive at night than those of humans. There are about 1.3 million ganglion cells in the human visual system; 1 to 2% of them are photosensitive.
Described here are vertebrate photoreceptors. Invertebrate photoreceptors in organisms such as insects and molluscs are different in both their morphological organization and their underlying biochemical pathways.
Rod and cone photoreceptors have the same basic structure. Closest to the visual field (and farthest from the brain) is the axon terminal, which releases a neurotransmitter called glutamate to bipolar cells. Farther back is the cell body, which contains the cell's organelles. Farther back still is the inner segment, a specialized part of the cell full of mitochondria. The chief function of the inner segment is to provide ATP (energy) for the sodium-potassium pump. Finally, closest to the brain (and farthest from the field of view) is the outer segment, the part of the photoreceptor that absorbs light. Outer segments are actually modified cilia that contain disks filled with opsin, the molecule that absorbs photons, as well as voltage-gated sodium channels.
The membranous photoreceptor protein opsin contains a pigment molecule called retinal. In rod cells, these together are called rhodopsin. In cone cells there are different types of opsins that combine with retinal to form pigments called photopsins. Three different classes of photopsins in the cones react to different ranges of light frequency, a differentation which eventually allows the visual system to distinguish color. The function of the photoreceptor cell is to convert the light energy of the photon into a form of energy communicable to the nervous system and readily usable to the organism: this conversion is called signal transduction.
The opsin found in the photosensitive ganglion cells of the retina that are involved in various reflexive responses of the brain and body to the presence of (day)light, such as the regulation of circadian rhythms, pupillary reflex and other non-visual responses to light, is called melanopsin. Atypical in vertebrates, melanopsin functionally resembles invertebrate opsins. In structure, it is an opsin, a retinylidene protein variety of G-protein-coupled receptor.
When light activates the melanopsin signaling system, the melanopsin-containing ganglion cells discharge nerve impulses which are conducted through their axons to specific brain targets. These targets include the olivary pretectal nucleus (a center responsible for controlling the pupil of the eye) and, through the retinohypothalamic tract (RHT), the suprachiasmatic nucleus of the hypothalamus (the master pacemaker of circadian rhythms). Melanopsin ganglion cells are thought to influence these targets by releasing from their axon terminals the neurotransmitters glutamate and pituitary adenylate cyclase activating polypeptide (PACAP).
The human visual system uses millions of photoreceptors. With the exception of melanopsin-containing photosensitive ganglion cells, ocular photoreceptors are the only neurons in humans capable of phototransduction. All photoreceptors in humans are found either in the outer nuclear layer in the retina at the back of each eye, while the bipolar and ganglion cells that transmit information from photoreceptors to the brain are in front of them. This inverted arrangement significantly reduces acuity, as light must travel through the axons and cell bodies of other neurons before reaching the photoreceptors. The retina contains two specializations to deal with this issue. First, a region at the center of the retina, called the fovea, containing only photoreceptors, is used for high visual acuity. Second, each retina contains a blind spot, an area where axons from the ganglion cells can go back through the retina to the brain.
For hundreds of years humans were thought to have only two types of photoreceptors in the retina: rods and cones. Both transduce light into a change in membrane potential through the same signal transduction pathway (see below). However, they differ in the nature of the opsin they contain, and their functions. Rods are used primarily to see at low levels of light, while cones are used to determine color, depth, and intensity. Furthermore, there are three types of cones, which differ in the spectrum of wavelengths of photons over which they absorb (see graph). Because cones respond to both the wavelength and intensity of light, a single cone cannot tell color; instead, color vision requires interactions of more than one type of cone (see below), primarily by comparing responses across different cone types.
Phototransduction is the complex process whereby the energy of a photon is used to change the inherent membrane potential of the photoreceptor. This change thereby signals to the nervous system that light is in the visual field.
Activation of a photoreceptor cell is actually a hyperpolarization; when they are not being stimulated, rods and cones depolarize and release a neurotransmitter spontaneously. In the dark, cells have a relatively high concentration of cyclic guanosine 3'-5' monophosphate (cGMP), which opens ion channels (largely sodium channels, though calcium can enter through these channels as well). The positive charges of the ions that enter the cell down its electrochemical gradient change the cell's membrane potential, cause depolarization, and lead to the release of the neurotransmitter glutamate. Glutamate can depolarize some neurons and hyperpolarize others, allowing photoreceptors to interact in an antagonistic manner.
When light hits a photoreceptive pigment within the photoreceptor cell, the pigment changes shape. The pigment, called iodopsin or rhodopsin, consists of large proteins called opsin (situated in the plasma membrane), attached to a covalently-bound prosthetic group: an organic molecule called retinal (a derivative of vitamin A). The retinal exists in the 11-cis-retinal form when in the dark, and stimulation by light causes its structure to change to all-trans-retinal. This structural change causes it to activate a regulatory protein called transducin, which leads to the activation of cGMP phosphodiesterase, which breaks cGMP down into 5'-GMP. Reduction in cGMP allows the ion channels to close, preventing the influx of positive ions, hyperpolarizing the cell, and stopping the release of neurotransmitters. Though cone cells primarily use the transmitter acetylcholine, rod cells use a variety. The entire process by which light initiates a sensory response is called visual phototransduction.
Unstimulated (in the dark), cyclic-nucleotide gated channels in the outer segment are open because cyclic GMP (cGMP) is bound to them. Hence, positively charged ions (namely sodium ions) enter the photoreceptor, depolarizing it to about -40 mV (resting potential in other nerve cells is usually -65 mV). This depolarizing current is often known as dark current.
The signal transduction pathway is the mechanism by which the energy of a photon signals a mechanism in the cell that leads to its electrical polarization. This polarization ultimately leads to either the transmittance or inhibition of a neural signal that will be fed to the brain via the optic nerve. The steps, or signal transduction pathway, in the vertebrate eye's rod and cone photoreceptors are then:
Thus, a rod or cone photoreceptor actually releases less neurotransmitter when stimulated by light.
ATP provided by the inner segment powers the sodium-potassium pump. This pump is necessary to reset the initial state of the outer segment by taking the sodium ions that are entering the cell and pumping them back out.
Although photoreceptors are neurons, they do not conduct action potentials with the exception of the ganglion cell photoreceptor.
Phototransduction in rods and cones is unique in that the stimulus (in this case, light) actually reduces the cell's response or firing rate, which is unusual for a sensory system where the stimulus usually increases the cell's response or firing rate. However, this system offers several key advantages.
First, the classic (rod or cone) photoreceptor is depolarized in the dark, which means many sodium ions are flowing into the cell. Thus, the random opening or closing of sodium channels will not affect the membrane potential of the cell; only the closing of a large number of channels, through absorption of a photon, will affect it and signal that light is in the visual field. Hence, the system is noiseless.
Second, there is a lot of amplification in two stages of classic phototransduction: one pigment will activate many molecules of transducin, and one PDE will cleave many cGMPs. This amplification means that even the absorption of one photon will affect membrane potential and signal to the brain that light is in the visual field. This is the main feature which differentiates rod photoreceptors from cone photoreceptors. Rods are extremely sensitive and have the capacity of registering a single photon of light unlike cones. On the other hand, cones are known to have very fast kinetics in terms of rate of amplification of phototransduction unlike rods.
|Used for scotopic vision||Used for photopic vision|
|Very light sensitive; sensitive to scattered light||Not very light sensitive; sensitive to only direct light|
|Loss causes night blindness||Loss causes legal blindness|
|Low visual acuity||High visual acuity; better spatial resolution|
|Not present in fovea||Concentrated in fovea|
|Slow response to light, stimuli added over time||Fast response to light, can perceive more rapid changes in stimuli|
|Have more pigment than cones, so can detect lower light levels||Have less pigment than rods, require more light to detect images|
|Stacks of membrane-enclosed disks are unattached to cell membrane directly||Disks are attached to outer membrane|
|20 times more rods than cones in the retina|
|One type of photosensitive pigment||Three types of photosensitive pigment in humans|
|Confer achromatic vision||Confer color vision|
A given photoreceptor responds to both the wavelength and intensity of a light source. For example, red light at a certain intensity can produce the same exact response in a photoreceptor as green light of a different intensity. Therefore, the response of a single photoreceptor is ambiguous when it comes to color.
To determine color, the visual system compares responses across a population of photoreceptors (specifically, the three different cones with differing absorption spectra). To determine intensity, the visual system computes how many photoreceptors are responding. This is the mechanism that allows trichromatic color vision in humans and some other animals.
The rod and cone photoreceptors signal their absorption of photons through a release of the neurotransmitter glutamate to bipolar cells at its axon terminal. Since the photoreceptor is depolarized in the dark, a high amount of glutamate is being released to bipolar cells in the dark. Absorption of a photon will hyperpolarize the photoreceptor and therefore result in the release of less glutamate at the presynaptic terminal to the bipolar cell.
Every rod or cone photoreceptor releases the same neurotransmitter, glutamate. However, the effect of glutamate differs in the bipolar cells, depending upon the type of receptor imbedded in that cell's membrane. When glutamate binds to an ionotropic receptor, the bipolar cell will depolarize (and therefore will hyperpolarize with light as less glutamate is released). On the other hand, binding of glutamate to a metabotropic receptor results in a hyperpolarization, so this bipolar cell will depolarize to light as less glutamate is released.
In essence, this property allows for one population of bipolar cells that gets excited by light and another population that gets inhibited by it, even though all photoreceptors show the same response to light. This complexity becomes both important and necessary for detecting color, contrast, edges, etc.
Further complexity arises from the various interconnections among bipolar cells, horizontal cells, and amacrine cells in the retina. The final result is differing populations of ganglion cells in the retina, a sub-population of which is also intrinsically photosensitive, using the photopigment melanopsin.
In 1991, Foster et al. discovered a non-rod non-cone photoreceptor in the eyes of mice, which was shown to mediate circadian rhythms. These neuronal cells, called intrinsically photosensitive retinal ganglion cells (ipRGC), are a small subset (~1-3%) of the Retinal Ganglion Cells located in the inner retina, that is, in front of the rods and cones located in the outer retina. ipRGCs contain a photopigment, melanopsin, which has an absorption peak of the light at a different wavelength (~480 nm) than rods and cones. Beside circadian / behavioral functions, ipRGCs have a role in initiating the pupil light reflex.
Dennis Dacey with colleagues showed in a species of Old World monkey that giant ganglion cells expressing melanopsin projected to the lateral geniculate nucleas. Previously only projections to the midbrain (pre-tectal nucleas) and hypothalamus (suprachiasmatic nucleus) had been shown. However a visual role for the receptor was still unsuspected and unproven.
In 2007 Farhan H. Zaidi and colleagues published their pioneering work using rodless coneless humans. Current Biology subsequently announced in their 2008 editorial, commentary and despatches to scientists and ophthalmologists, that the non-rod non-cone photoreceptor had been conclusively discovered in humans using landmark experiments on rodless coneless humans by Zaidi and colleagues The workers found the identity of the non-rod non-cone photoreceptor in humans to be a ganglion cell in the inner retina as had been shown previously in rodless coneless models in some other mammals. The workers had tracked down patients with rare diseases wiping out classic rod and cone photoreceptor function but preserving ganglion cell function. Despite having no rods or cones the patients continued to exhibit circadian photoentrainment, circadian behavioural patterns, melanopsin suppression, and pupil reactions, with peak spectral sensitivities to environmental and experimental light matching that for the melanopsin photopigment. Their brains could also associate vision with light of this frequency.
In humans the retinal ganglion cell photoreceptor contributes to conscious sight as well as to non-image-forming functions like circadian rhythms, behaviour and pupil reactions. Since these cells respond mostly to blue light, it has been suggested that they have a role in mesopic vision. Zaidi and colleagues' work with rodless coneless human subjects hence also opened the door into image-forming (visual) roles for the ganglion cell photoreceptor. It was discovered that there are parallel pathways for vision - one classic rod and cone-based arising from the outer retina, the other a rudimentary visual brightness detector arising from the inner retina and which seems to be activated by light before the other. Classic photoreceptors also feed into the novel photoreceptor system, and colour constancy may be an important role as suggested by Foster. The receptor could be instrumental in understanding many diseases including major causes of blindness worldwide like glaucoma, a disease which affects ganglion cells, and the study of the receptor offered potential as a new avenue to explore in trying to find treatments for blindness. It is in these discoveries of the novel photoreceptor in humans and in the receptors role in vision, rather than its non-image-forming functions, where the receptor may have the greatest impact on society as a whole, though the impact of disturbed circadian rhythms is another area of relevance to clinical medicine.
Most work suggests that the peak spectral sensitivity of the receptor is between 460 and 481 nm, though a minority of groups reported it being lower as far as 420 nm. Steven Lockley et al. in 2003 showed that 460 nm wavelengths of light suppress melatonin twice as much as longer 555 nm light. However, in more recent work by Farhan Zaidi et al., using rodless coneless human, it was found that what consciously led to light perception was a very intense 481 nm stimuli - this means that the receptor in visual terms enables some rudimentary vision maximally for blue light.