Review Article

Retinal phototransduction

Gurdeep S. Mannu, MSc, MRCSEd.

ABSTRACT T he eye is a complex structure in terms of cell types.

It is due to this complexity that much remains
unknown regarding the neurobiology of vision. This
‫تعد حاسة البصر من أهم احلواس التي متدنا بكم هائل من‬ article will summarize the current understanding of
‫ الفوتونات هي الشكل‬.‫املعلومات فيما يخص العالم اخلارجي‬ light transduction within the eye. The eye allows the
‫األولي والذي من خالله تصل املعلومات لشبكية العني ويتم‬ ‘collection’ and detection of light and may be analogous
with a camera. The eye lens focuses light onto an area
‫ترجمتها وتعتبر جزيئات من إشعاع الطاقة لطول موجي معني‬ at the back of the eye called the retina (much like a film
‫ فإن الدماغ نفسه مييز‬،‫ ومع ذلك‬.‫منبعث أو منعكس من محيطنا‬ or photosensitive chip in a camera). The retina is the
‫املعلومات في اإلشارات الكهربائية عبر اجلهد الفعلي والتغير في‬ most important component of the eye for the detection
‫ في هذا املقال سوف نسلط الضوء‬. ‫التدرجات الكهروكيميائية‬ of all light entering the eye and hence is very specialised
.‫على العملية التي تضم انتقال الفوتونات إلى جهد كهربائي‬ in terms of the structure and arrangement of the cells
present here. The retina of the eye is composed of 4
‫كما يلخص هذا املقال التقدم احلديث في فهم هذه اآلليات‬ different light-sensitive cells divided into rod cells as well
‫املعقدة وإعطاء نظرة عامة عن اجلزيئات األساسية الداخلة في‬ as 3 types of cone cell (cone cells being differentiated
.‫رؤية علم األعصاب‬ by the nature of the opsin pigment that they contain).
The 4 types of light-sensitive cells, by virtue of their
Vision is perhaps the most important of all our senses, pigments and intracellular machinery, are the focal
and gives us an immense amount of information points of the transduction process, which converts light
regarding the outside world. The initial format in energy into electrochemical energy. It is due to this
which this information reaches the retina are photons; function that these cells are termed photoreceptors.1
particles of energy radiation of a given wavelength These cells are unique in their design and structure.
emitted or reflected from our surroundings. The They are long elongated neuronal cells stacked tightly
brain itself however, perceives information in one next to the other like miniature skyscrapers with
electrical signals via action potentials and changes in their dendritic ends facing in the direction where light
electrochemical gradients. The processes involved in is entering the eye. This is followed by a ‘swelling’ in the
the transduction of photons into electrical potentials neurone for the cell’s nucleus. Deeper into the retina
will be the focus of this article. This review article is another swelling for the cell’s organelles, especially
summarizes the recent advances in understanding mitochondria, which cater to the immense energy
these complex pathways and provides an overview of requirements for the cell. Finally, there is a series of a
the main molecules involved in the neurobiology of thousand or so ‘discs’, each side of which containing
vision. roughly eighty thousand pigment molecules.2 It is these
pigment molecules that will be the focus of this article.
Neurosciences 2014; Vol. 19 (4): 275-280
The photoreceptor cells are well vascularized with a
constant and steady flow of blood, sustaining constant
From the Academic Medicine Department, Norfolk and Norwich external ion gradients and providing a maintained
University Hospital, Norfolk, United Kingdom. supply of substrate molecules. The neurone’s dendrites
are synapsed upon by bipolar cells, although the exact
Address correspondence and reprint request to: Dr. Gurdeep S. Mannu,
Academic Medicine Department, Norfolk and Norwich University
Hospital, Colney Lane, Norwich, Norfolk NR4 7UY, United
Kingdom. Tel. +44 (1603) 286286. Fax. +44 (1603) 287211. Disclosure. The author declares no conflicting interests,
E-mail: Gurdeepmannu@gmail.com support or funding from any drug company.

www.neurosciencesjournal.org OPEN ACCESS Neurosciences 2014; Vol. 19 (4) 275

 Phototransduction of vision … Mannu

nature of this synapsing depends on the cell involved. sequence that follows, resulting ultimately in a sequence
Rod cells particularly show great spatial summation of electrical signals being sent to the brain.4 The brain
(with one bipolar cell synapsing with many rod cells). will receive and process information according to the
Although this summation considerably reduces visual frequency and pattern of these signals.5 This article
acuity, it does greatly increase visual sensitivity in low will describe how light energy is ‘captured’ chemically,
light conditions. Cone cells, however, have a one-to-one converted into electrical energy, and which intracellular
relationship with their respective bipolar cells, creating machinery, and chemicals are used in this process.
high visual acuity, but function poorly in low light Literature review. A 2-step process utilizing a
conditions. There is also differentiation between Medline/PubMed systematic search was conducted. The
the position of both cone cells and rod cells within initial search was undertaken using elementary phrases
the surface of the retina itself. Cone cells are more including “neurobiology of vision,” “light transduction,”
focused; namely, they have a greater concentration in “intracellular mechanism,” and “retinal pigment.” Only
an area known as the fovea (or ‘area centralis’), which the most recent literature in the field was required so the
is where light is typically focused by the cornea, lens, time-window for the literature review was restricted to
and refractive fluid within the eye. The fovea requires the past 30 years (1983-2013). The resultant abstracts
a greater number of high acuity cells to differentiate were analyzed and appropriate papers were selected.
and perceive the much larger number of photons being The secondary search was performed by (1) using the
funneled here. Rod cells lie circumferentially and aid reference lists of the chosen articles, and (2) by using
with peripheral vision. PubMed weblinks for related articles. The studies were
The first stage in transducing light into a form the selected if they were in English language and included
brain can comprehend is the ‘capturing’ of light energy the appropriate topics. The search produced over 3,300
into a chemical format. This is achieved by the presence published papers on the topic of the neurobiology of
of various light ‘pigment’ molecules within the outer vision. The abstracts of these were screened and all
segments of these receptors. With advances in the theory papers relating to the intracellular signal transduction
of wave-particle duality, light is now regarded as being or mechanisms of action were selected.
transmitted through space in the form of tiny packets Current status of knowledge. Each of the 4 types of
of energy (photons). The energy of each photon varies photoreceptors has unique pigment molecules which,
depending on its frequency (E=hF; where E=energy, when absorbing light of a certain frequency, will initiate
F=frequency, h=Planck’s constant). High-energy a distinctive conformational change in structure. For
photons have higher frequencies, and low frequency many years the question that interested neuroscientists
photons hence have less energy. The higher a photon’s and researchers in this field was how these different
frequency, the lower its wavelength, and different retinal photopigments actually absorbed different frequencies
cells are sensitive to particular wavelengths. When of light. Advances in molecular techniques have
photons between 400 to 780nm in wavelength enter revealed that the answer to this lies in the chemical
the eye, they collide with the pigment molecules inside composition of each pigment. All of these individual
these retinal cells and cause various conformational pigments contain an aldehyde of vitamin A called
changes to occur within them.3 These photochemical retinaldehyde (abbreviated to retinal) in addition to
changes occur as the wavelength of light is converted one other component called opsin.6 It is this opsin that
into its equivalent in chemical energy. These altered differentiates the different types of photoreceptor.4 Rod
molecules are responsible for the intracellular cascade cells contain rhodopsin (Figure 1), which absorbs light

Figure 1 - The chemical structure and formation of rhodopsin. C - carbon, H - hydrogen, O - oxygen, N - nitrogen, R - rest of the molecule.

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 Phototransduction of vision … Mannu

with a wavelength of 500 nm (namely, in the blue-green associated with a lack or disruption of one of the 3
region of light).7 However, cone cells contain 3 different opsin pigment molecules found in the cone cells at the
pigments, called iodopsins; namely, erythrolabe, very start of the transduction pathway.11 Since each of
chlorolabe, and cyanolabe. Each of these is sensitive to these molecules absorb a different wavelength of light
different frequencies of light; erythrolabe is liable for for human trichromatic vision, a lack in any of them
absorption of photons at a wavelength of 565nm (red would mean perception of that particular range of the
light), chlorolabe can absorb light of 535nm wavelength light spectrum would be lost.11 A problem with each of
(green light), and finally cyanolabe absorbs light of a the pigments results in different pathologies. A defect
maximum wavelength of 440nm (in the blue color end in the erythrolabe pigment results in ‘protanomaly’ or
of the spectrum).8 Despite the variation in the pigments red-green color blindness. Chlorolabe defects result
involved, the reaction that follows light interaction with in ‘deuteranomaly’ (red-green color blindness), and
the pigment is consistent. Opsin is bound to retinal by cyanolabe defects result in yellow blue color blindness,
a covalent double bond between a carbon and nitrogen or ‘tritanomaly’. Genetic changes in pigment and
atom to form rhodopsin.9 When light contacts the retinal arteriolar attenuation are seen in retinitis pigmentosa.
molecule it causes a conformation change to occur at Rod cells are affected early in the condition and due
the eleventh carbon atom along the chain (Figure 2). to the rod cells higher sensitivity to light, the loss of
This causes the molecule to revert from its 11-cis form, nighttime vision is an early symptom of the condition
to an 11-trans state.10 This change coincides with a alongside gradually worsening loss of peripheral vision.
change in the molecule’s chemical properties since the Many distinct defects in DNA have been isolated
11-trans form does not bind to opsin. and related to retinitis pigmentosa. Most of these are
Pathologies can develop at any stage during the light transmitted by autosomal recessive inheritance; however,
transduction pathway, and thus the pigment molecules a proportion are autosomal dominant (30-40%) and
are not immune to this. The most common abnormality X-linked (5-15%).12
at this stage of the transduction process is that of ‘color The light-dependent cascade. Under dark conditions,
blindness’. Color blindness is a well-established term photoreceptors are constitutively continuously present
used to describe the lack of perception of a certain in a depolarized state, thus continuously releasing
wavelength (or ‘color’) of light. This can result from a glutamate across the synaptic cleft.13 Photons actually
defect in the higher stages of the perceptual process, for result in these photoreceptors becoming hyperpolarized,
example, in the lateral geniculate nucleus parvocellular and as such, signal the changes in electrical potentials in
pathway. However, color blindness is most commonly cells. For a change in the electrochemical potential of
the photoreceptor cell to occur, ion channels must either
be opened or closed. Within the cell, cyclic guanosine
monophosphate (cGMP)14 is a molecule responsible for
closing of sodium and calcium channels.10,15 The more
cGMP there is within the cell, the more channels are
closed and the lower the movement of ions and thus
reduced electrical activity within the cell. The cGMP is
inactivated by the enzyme cGMP phosphodiesterase in a
hydrolysis reaction.16 Hence, the lower the concentration
within the cell of cGMP phosphodiesterase enzyme;
the more cGMP will be present and thus, the more ion
channels will be closed. However, the more there is of
this enzyme, the fewer channels will subsequently close
(and there will be more open channels). After contact
of light with the retinal molecule, the resulting 11-trans
form of retinal can no longer bind to opsin, and
thus dissociates from this molecule and moves to the
membrane. Here, 11-trans retinal binds to guanosine
triphosphate (GTP)-binding protein molecules named
Figure 2 - Light causes a conformational change in the retinal molecule
transducin, and activates them.17 The involvement of
from the 11 cis-retinal to the trans-retinal. C - carbon, H - transducin is a vital step in the cascade. Transducin
hydrogen, O - oxygen. consists of 3 subunits; namely, the alpha, beta, and

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 Phototransduction of vision … Mannu

gamma subunits. The alpha subunit contains a molecule transporter in the outer part of the photoreceptors
of guanosine diphosphate (GDP). The 11-trans retinal closes due to the increase in cGMP, and thus; as a result,
causes the alpha subunit to give up its GDP molecule the influx of positively charged calcium and potassium
in exchange for a GTP molecule. This exchange causes ions ceases. However, despite this event, the potassium
the entire alpha subunit to dissociate from the rest of transmembrane transporter is not cGMP gated,
the complex,18 and to move to interact with the target and thus remains open. The consequence of this is a
protein enzyme cGMP phosphodiesterase. Thus, as continuing outward movement of potassium ions from
mentioned earlier this enzyme is responsible for the the photoreceptor into the interstitial environment, and
hydrolysis of cGMP to an inactive form and hence as such, a net decrease in intracellular charge. This net
an increase in the influx of sodium and calcium ions outward flow of singly positive potassium ions reduces
(Figure 3). Since the photoreceptor remains idle in a the cell potential and hence hyperpolarizes the cell by
constitutively depolarized state, all signals must be approximately 1mV, known as the photovoltage.20 It is
signaled by a net hyperpolarization (the exact reverse via a lack of depolarization (by hyperpolarization) that
of what would be the case in many other parts of the information is coded in electrical potentials describing
human body). At resting conditions (when there is no the contact of photons of different frequencies with
light), there is an ‘equilibrium’ of ion charge movement. retinal pigment molecules.
In other words, the net movement of calcium and Deactivation of the cascade. It is necessary for this
sodium ions from the interstitial fluid into the outer transduction system to reset itself in order for further
segment of the photoreceptor is equalized by an outward signals to be sent. Our environment is ever changing
movement of potassium ions in the inner segment.19 As and adapting, and in order for us to successfully survive
a result, the cell has a net current of around -34pA due within these surroundings, we must anticipate and
to the net flow of calcium and sodium ions through adapt as well. The speed by which we react to changing
the cGMP-gated transmembrane transporter channel stimuli from our environment is of vital importance,
into the outer segment.20 When the photoreceptors and this relies on the speed by which we may perceive
are exposed to photons; namely, the eyes are present in changes occurring. This perception is dependent on the
light conditions; a change in the electrical activity of the ‘resetting’ of the transduction cascade to allow it to be
cell occurs. Through the guanylate cyclase transduction reactivated and ‘triggered’ once again. This allows any
pathway of intermediates, the calcium/potassium changes occurring between the 2 inputs in time to be

Figure 3 - A schematic summary of the light conduction pathway. GDP - guanosine diphosphate, GTP - guanosine triphosphate, GMP - guanosine
monophosphate, Na+ - sodium ions, Ca2+ - calcium ions, K+ - potassium ions.

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 Phototransduction of vision … Mannu

compared and extrapolated by the brain in order to well as their interrelationships with each other and the
explain what exactly is occurring in the outside world. pathways through which they bring about their actions.
An accurate, yet simple analogy of this is a film However, this is a rapidly evolving field with powerful
tape. The tape consists of a series of static, non-moving techniques being developed to explore the genetic
pictures, which once perceived one after the other at coding for the molecules involved in the transduction
sufficient speed may delude the brain into believing process in recent years. This will no doubt provide us
that animation is occurring; this is in fact, exactly what with deeper knowledge of the roles of the molecules
happens continually in human perception of the outside described in this article. The fields of signal conduction
world. The rate at which a static image may be perceived and signaling in vision are likely to continue to be the
as moving depends on the ‘reset’ time for the light source of interest and focused research with an ever-
transduction system to reset itself. This is referred to as evolving picture of the underlying mechanisms.
the critical fusion frequency, and in humans, in bright
lighting conditions this may be around 60Hz. It should References
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