Physiology, Vision

Article Author:
Arturo López de Nava
Article Author (Archived):
Anisha Somani
Article Editor:
Baby Salini
7/13/2019 3:40:13 PM
PubMed Link:
Physiology, Vision


Vision is one of the five senses of the body. It's a way used by our body to interpret reality. Our body works as a filter for what is happening out there; vision is one of the most important senses for this task. Humans had what is called "dichromatic vision" in the past; that means we could see only two colors in the color wave spectrum. About 30 million years ago, the trichromatic part of vision came to existence. It is believed by scientists that this modality of vision appeared because of environmental adaptation. We can see black, white, red, green and blue wavelength colors and the colors between this spectrum; and the retina and the brain are equipped to differentiate them daily. What happens between an object and a synapse in the most posterior part of the brain is the fascinating journey that we will go over. 

Issues of Concern

Physical Properties of Vision

Vision cannot be discussed without knowing the physical properties of optics. The eye receives light that then is traduced into energy. That energy goes into the optic nerve as an action potential and travels to specific nuclei in the brain, where it is processed. But, how does that light get into the eye to be processed into an action potential to be sent to the brain?

The eye is composed of a series of lens and spaces that give focus to images, just as a camera does. It is composed, of vitreous humor, aqueous humor, the crystalline lens, and the cornea, and each of these has its own refraction index (the average being 1.34, because of the content of these tissues). Light travels in the air in the form of waves. The term Refraction Index refers to the relation between light´s airwave velocity and the velocity when it travels across an object. It travels at a velocity of 300,000 km/s in the air.

Light´s refraction index on air is 1. This refraction index changes when light travels into objects as it gets slower going through glass, for example. With all of the above then we can infer that light gets slower and its trajectory gets modified slightly as it goes through the eye across all of its lenses and cameras and it can be also inferred that every disease that affects any of these lenses in the eye will significantly alter vision.[1][2]

When light waves come across a spherical lens, these waves tend to converge into a focal point, and in the eye, this focal point is projected into a single area which is the retina. For this to be accomplished, the crystalline lens has to do its work. The lens is a capsule filled with water and filamentous proteins; it has a stretched configuration in resting. So, if we imagine this light wave coming across this stretched, very flat lens, then we can assume that light will go farther into the eye because the refraction index is lower. With this crystalline configuration, we can see things clearly even though they are far away because they get projected further into the eye. But when we focus a closer object, then the lens has to change its shape into a more spherical one, in order to the light waves to converge into a closer point, as discussed earlier. This is accomplished by the parasympathetic system. So the nervous system has a role here! Yes, because the parasympathetic system is in charge of constricting some muscle fibers called the ciliary muscle system. These muscle fibers make the crystalline lens to go spherical, as will be discussed later. All of these processes have to be intact for the accommodation reflex to be done.[3]


At the heart of these organic devices is the visual pigment rhodopsin - a modified molecule of vitamin A. This molecule consisting of allylic carbons contains a great deal of conjugated, pi electrons. Recall in organic chemistry an allylic group is a carbon atom singly bonded to another carbon atom which is in turn double bonded to a carbon atom. The electrons within these alternating pi bonds of the rhodopsin molecule are not as well-defined as the electrons in a saturated carbon chain (no double bonds) or in a singly double-bonded (think simple structure) molecule of ethylene (aka ethene, C2H4).[4]

Rhodopsin consists of the protein scotopsin and the chromophore 11-cis-retinal, covalently bound between one of the protein's lysine residues and the protonated Schiff base (the nitrogen with a positive charge) within the chromophore. The chromophore is the light-absorbing center. It functions by facilitating the absorption of photons to potential energy--this is where the state is changing--akin to the reaction centers of chlorophyll. Chemical energy is produced, and in this case, the absorption of photons supplies the energy needed to enter the transition state, which allows isomerization of the chromophore molecule from cis to trans (180-degree rotation). Although the reaction mechanism is involved, it can be summarized as:

  • Photons elevate electrons within the conjugated pi system to higher energy orbitals (dictated by the level of resonance within the chromophore).
  • The molecule is allowed to rotate about the double-bond.
  • By the end of the mechanism, the excited electrons' energy levels have fallen back to the ground state.[5]

At the reaction completion chromophore has changed to the more stable trans configuration about one of its double bonds. With the protein bound nitrogen fixed in space, this results in translocation of five angstroms for the molecules' ring. Thus within rhodopsin, light absorption leads to a chemical reaction that forces part of the rhodopsin molecule to translocate, by changing protein conformation and exposing active sites. This activated form of rhodopsin is known as metarhodopsin II. Before it can get to the metarhodopsin phase, the molecule has to change several times into several forms, which change very rapidly but are not the active and exciting form of rhodopsin and these changes in the molecule occur in the matter of milliseconds. Metarhodopsin II activates many copies of the G protein transducin (by replacing transducin's GDP with GTP). Many activated transducin complexes activate cyclic nucleotide phosphodiesterase (PDE), which can itself hydrolyze 1000 molecules of cGMP to 5'-GMP per second. cGMP-gated channels in the plasma membrane of these rods (or cones) allow sodium ion influx at high cGMP concentrations; this is balanced by cation exchanger-mediated glutamate efflux, maintaining cell depolarization (dark conditions). At low cGMP concentrations, these channels close, stopping sodium ion influx and reducing glutamate efflux, all leading to cell hyperpolarization (light conditions). Thus light-induced rod/cone state changes lead to hyperpolarization of the photoreceptor cells. Conversely, photoreceptor cells without the presence of light exist in the depolarized state.[6]

Light response is a one-to-one effect. The enzyme rhodopsin kinase quickly binds metarhodopsin II, phosphorylating and halting its activity. The protein arrestin binds phosphorylated metarhodopsin II. Metarhodopsin II is unstable and will split within minutes, leading to opsin and free trans-retinal. Trans-retinal is transported to pigment epithelial cells that convert trans-retinal back to 11-cis-retinal, which eventually is recombined with opsin within cones/rods to reform rhodopsin. Guanylate cyclase restores cGMP concentration, and the cone/receptor is ready to respond to another light exposure event.

Additionally, phototransduction is subject to regulation by a calcium-mediated pathway to quickly diffuse a large gradient response, in such circumstances as sudden flashes of light in the dark. In dark conditions, intracellular calcium level is high due to calcium diffusion through cGMP-gated channels. Lack of frequent light response allows more calcium to enter the cell per second, due to high intracellular cGMP concentrations. Calcium ion binding to rhodopsin kinase increases the rate of rhodopsin phosphorylation, reducing transducin activation. Calcium ion binding to guanylate cyclase accelerates the restoration of cGMP concentration. And calcium ion binding to calmodulin increases cGMP affinity to its gated channel.


The surface of the human retina contains about three million cones and one hundred million rods, but there are just 1.5 million ganglion cells; meaning that for every ganglion cell, there are sixty rods and two cones. Cones transmit color information, rods focus on greater sensitivity to low-light conditions. However, this relation tends to be different depending on the part of the retina that we examine. We have the central retina, for example, where there are almost only cones and a lot of ganglion cells making synapses there, which explains why the central retina is the “perfect vision” region of the eye. In contrast, go to the peripheral retina, and you will find that there are more rods than cones and the visual acuity gets lower. Ganglion cells, therefore, come in different flavors: W, X, and Y ganglion cells. Some of these are in charge of detecting changes in color intensity (cones), and some are more specialized in detecting changes in contrast (rods) depending on the part of the retina in which they are receiving the stimuli.

The interneural connections of ganglia (bipolar cells) allow low-level visual processing, adjusting the gain of the signal to transmit light gradients rather than absolute light intensity. This process is important because relative differences within the light field are behaviorally more significant; the object's visual patterns are emphasized rather than providing strictly hit/miss signal information. It's also crucial because rods/cones can distinguish light intensity varying by ten orders of magnitude, but the ganglia of the optic nerve can only transmit about 1% of this range.[7]

Color vision results from the combination of signals from three visual pigment types within cones: that of red, green, and blue, which correspond to cone types L, M, and S (RGB-LMS). Those colors correspond to the wavelengths of peak light absorption intensities of the modified chromophores. Remember, resonance is vital. Such modifications are referred to as Schiff-base modifications; further, they can be classified as redshift Schiff-base modification or blueshift

 Schiff-base modification, denoting whether shifted toward peak absorptions at longer or shorter wavelengths, respectively. The average absorption maxima for 11-cis-retinal occurs at a wavelength of 380nm. If an experimenter were to expose 11-cis-retinal to EM radiation at this wavelength, the 11-cis-retinal would most readily absorb energy in contrast to an EM radiation at a wavelength of 280nm. Studies have demonstrated that when retinal is chemically modified to exhibit a more conjugated, distributed pi-electron system, redshift Schiff-base modification is observed. This means the visual pigment exhibits more significant resonance than before and light is maximally absorbed in a longer wavelength. In contrast, when retinal is chemically modified to exhibit a less conjugated, less distributed pi-electron system, blue shift Schiff-base modification is observed. Here the visual pigment exhibits less significant resonance than before and light is maximally absorbed in a shorter wavelength. L cones have peak absorptions at 555-565 nm, M cones at 530-537 nm and "S" cones at 415-430 nm.[8]

Thus color vision arises from the shifted cones' peak absorption levels and ultimately the brain's interpretation of the composition of these points of wavelength absorption. The entire pathway is sometimes referred to as the retinoid cycle.

Organ Systems Involved

The sense of vision involves the eye and the series of lenses of which it is composed, the retina, the optic nerve, optic chiasm, the optic tract, the lateral geniculate nuclei in the thalamus and the geniculocalcarine tract that projects to the occipital cortex.


The information coming from the ganglion cells of the retina get into the optic nerves, then the action potentials go into a region called optic chiasm (where the optic nerve fibers of both eyes cross in the middle line and then form the optic tract). The direction of the visual information here is slightly different as the ipsilateral temporal side of it passes directly into the ipsilateral part of the cortex, that means, it doesn´t get deviated; whereas the nasal part of vision gets crossed to the contralateral part of the brain, going to the opposite occipital cortex. So passed the optic chiasm, every optic tract has information of both eyes, having a temporal ipsilateral part of the data and a nasal contralateral part of it. This visual information then gets integrated into the thalamus, in the lateral geniculate nuclei and then projects into the visual cortex. Before visual information gets into the thalamus, it can get deviated into other structures such as the pretectal nuclei and the superior colliculus in the brainstem to generate visual reflexes to focus into certain objects or to the suprachiasmatic nuclei of the hypothalamus to regulate the circadian rhythms and so on.[9][10]

When the information comes to the thalamus, it has to be ordered like paperwork in an office. So, to accomplish this task, the lateral geniculate nucleus has six layers of neural networks so that information can be integrated and put in order. Layers II, III, and V receive information from the ipsilateral temporal visual field and layers I, IV and VI receive information from the contralateral nasal visual fields. To make it more interesting, layers I and II are conformed of magnocellular neurons, and layers III, IV, V, and VI are adapted of parvocellular neurons. What´s up with that? Well, it turns out that the retina has these types of neurons too, which are subtypes of the ganglion cells; the ones that receive all the information at the end of the retina visual pathway. In the retina, the “magnocellular” type ganglion cells receive information about black and white contrast and rapid changes in object positions, and the “parvocellular” type neurons receive information about color. So the lateral geniculate nucleus has two layers of neurons dedicated exclusively to the integration of information about black and white contrast and visual field changes and four layers assigned to the combination of color. From here, all of these color and contrast cues go to the visual cortex, where the information is then processed and interpreted.[11]

Clinical Significance

Improper Color Vision Recognition/Color Blindness

Many forms of color vision recognition abnormalities are present in the population, with most having a genetic origin (congenital). Very few individuals are truly color blind, but instead, see a disrupted range of colors. The most common forms are protanopia and deuteranopia, conditions arising from loss of function of one of the cones, leading to dichromic vision. Protanopia is the loss of L cones (red) resulting in green-blue vision only. Deuteranopia is the loss of M cones (green) resulting in red-blue vision only. Both are X-linked alleles, therefore almost exclusively occurring in males, occurring with a prevalence of 1%. Loss of "S" cones does rarely occur in 0.01% of males and females. In these cases, one of the cones does not function, and physically in its place, one of the others is expressed.

Similar to above, but not as severe in its symptoms, is the condition anomalous trichromatic vision (tritanomaly), where all three cones are present but color vision is aberrant. The two common forms, protanomaly and deuteranomaly, result in L or M cones, respectively, being replaced with a cone of intermediate spectral tuning. Both are X-linked and occur in 7% of males.

Diseases affecting color vision but not affecting cones  

In addition to disorders of proper color recognition, many diseases in vision display phototransduction defects that affect many portions of the signal pathway and its regulation. Here, not only is color vision function lessened but monochromatic as well.

1. Stationary Night Blindness (CSNB)

One such disease is congenital stationary night blindness. It is a genetic defect resulting in functional cones but dysfunctional rods. In this disease, many potential culprits have been identified including abnormal rhodopsin, arrestin, rod transducin, rod phosphodiesterase, and rhodopsin kinase. Studies have demonstrated that in some populations of this disease rods are permanently outputting light signal. In CSNB, b-waves are reduced (in CSNB type 2) or absent (in CSNB type 1) during an electroretinogram (ERG). There are currently no treatments for this disorder. 

2. Retinitis Pigmentosa (RP)

Another disease affecting rod function is retinitis pigmentosa which is a progressive degeneration of the retina leading to blindness, of genetic origins. Frequently, it begins in early phase as night blindness, and eventually progresses to loss of vision from the periphery leading to the center, manifesting as tunnel vision. These clinical manifestations are connected with faulty rod functioning; if cones begin to be affected, then blindness eventually results. RP is characterized by reduced or absent a-waves and b-waves during an ERG. It has a prevalence of 1 in 3500 individuals.

3. Malnutrition-Associated

Deficiency in the essential nutrient vitamin A leads to night blindness, and can eventually lead to permanent blindness through deterioration of the receptor outer segments.

Experimental Therapies

Currently, there are no FDA-approved treatments for CSNB or RP. However, there is the promise of gene-therapy interventions on the horizon. The recent completion of several phases I/II clinical trials of retinal gene therapies utilizing Adeno-associated virus (AAV) have shown moderate success in preventing disease onset and progression for several years.

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      Contributed by Arturo López de Nava, MS


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