The role of ultrafast processes in human vision This minireview discusses the process of vision which begins with the absorption of a photon of light by rhodopsin in rod cells. Rhodopsin consists of the protein opsin bound to the light-sensitive molecule retinal. Upon photon absorption, the retinal undergoes an ultrafast cis-trans isomerization within 200 femtoseconds, initiating a chain of reactions that converts rhodopsin to various intermediates and ultimately triggers an electrical signal to the brain. This initial isomerization is one of the fastest biological reactions known and occurs with high efficiency due to the protein environment of rhodopsin. Advances in ultrafast spectroscopy have provided insights into the mechanisms and

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MINIREVIEW
This journal is © The Royal Society of Chemistry [year] [journal], [year], [vol], 00–00 | 1
The role of ultrafast processes in human vision
Hassen Iqbal and Vas Stavros*
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
DOI: 10.1039/b000000x
Human vision occurs through a process known as phototransduction, which is the conversion of light5
energy into electrical and chemical signals. The first step in phototransduction is an ultrafast process that
occurs in femtoseconds. In this minireview we will discuss what happens when a photon of light enters
the photoreceptors in the eye. We will focus mainly on the rhodopsin pigment (also known as visual
purple) contained in the rod photoreceptor found in rod cells that are responsible for black and white
vision.10
1. Introduction
Human vision occurs through phototransduction, which is the
conversion of light energy into electrical signals. This process
occurs in two kinds of photoreceptor neurons known as the rod
cells and the cone cells.1
Humans have a trichromatic visual15
system, which consists of rod cells and three kinds of cone cell
each containing a slightly different pigment. Rod cells are more
sensitive to light, as several cells share a connection to single
optic nerve, and are responsible for our night time vision.2
A rod
cell is sensitive enough to respond to one photon of light and is20
responsible for our black and white vision.3
Cone cells contain
less photopigment than rod cells and require more light to
respond as each cone cell has a single connection to an optic
nerve however this increases its visual acuity.4
There are three
kinds of cone cells, which each contain a different pigment that25
respond to different wavelengths of light. The first kind responds
to long wavelengths of light, mostly red light peaking at
wavelengths 564 to 580 nm and is often designated L for long.
The second type responds to light of a medium-wavelength,
mostly green light peaking at a wavelength of 534–545 nm, and is30
abbreviated M for medium. The third type responds to short-
wavelengths of light, mostly light of a bluish colour peaking at a
wavelength of 420–440 nm, and is designated S for short.5
The
difference in the strength of the signals received from the three
types of cells allows the brain to interpret colour.6
There are35
approximately an average of 4.5 million cone cells contained in
the human retina as opposed to 90 million rod cells.7
Rod cells
contain a pigment protein called rhodopsin and cone cells contain
pigment proteins called iodopsins, which are similar in structure.4
They all consist of an opsin protein, which varies in a few amino40
acids for each.
Retinal is a common co-factor and contains the chromophore that
responds to light.
Fig. 1 The conversion of 11-cis-retinal to all-trans-retinal45
2. Background
Rhodopsin is the pigment contained in the rod cell and is
primarily responsible for the perception of light. Rhodopsin
consists of a protein known as opsin that is bound to the co-factor
retinal.8
The retinal contains a chromophore, which is in a region50
where the energy difference between two different molecular
orbitals lies within the visible spectrum. Thus visible light is
absorbed when it hits the chromophore by exciting
an electron from its ground state to its excited state.5
55
60
Hassen Iqbal was born in Southampton in 1992. He completed his A levels in 2010. He is currently studying in his second
year of his four year MChem Chemistry degree at the University of Warwick. He has taught chemistry at an East London
tuition centre in 2011. He is a member of Radio Warwick and works with a presenter in a show. His areas of interest
mainly consist of physical chemistry, particularly chemistry related to how molecules interact with light. He also has a
strong interest in polymer chemistry and itsapplications.
Hassen Iqbal

2. 2 | Journal Name, [year], [vol], 00–00 This journal is © The Royal Society of Chemistry [year]
Retinal has a broad band of absorbance in the visible spectrum
that peaks at 500 nm.9
The chromophore is at the cis double bond
between carbon11 and carbon12 of the retinal. This undergoes
ultrafast isomerisation to convert 11-cis-retinal to all-trans-retinal
(figure 1)10
. The primary reaction in vision is the cis to trans5
isomerisation that leads to a chain of events leading to the
submission of electrical signals to the brain, which will be
explained in detail further down. George Wald first discovered
the chromophore in the 1930s, through extracting three hundred
frog retinas and isolating retinal. Yoshizawa and Wald predicted10
that cis-trans isomerisation lead to a conversion of rhodopsin to
bathorhodopsin that existed on a higher energy level. They did
this by warming rhodopsin slowly and they were able to indentify
several intermediate stages. In recognition of Wald’s discoveries
that were fundamental to understanding the biochemistry15
involved in vision, he was awarded the Nobel Prize in Physiology
or Medicine in 1967.11
Femtosecond laser pulses in the 1990s
allowed more detailed examination of the process.11
3. Transient-absorption spectroscopy20
Transient absorption is used to probe intermediates that have a
very short lifetime. The molecule is promoted temporarily to an
upper excited state. To measure the absorption of a transient
molecule a pulsed laser is required to generate molecules into an
excited state and then a second laser pulse is used to probe the25
absorption.12
The technique used for transient absorption
spectroscopy is known as the pump-and-probe method. First of
all a weak pulsed laser (pump beam) excites the sample at a
wavelength where ground state absorption occurs. The sample is
then targeted with a probe beam with an extremely short time30
delay. This excites the sample to an upper excited state and then
the difference between the two absorbencies can be calculated.
The probe beam is often obtained by splitting the pump beam,
which is then targeted at certain materials to generate pulses in
the region of interest. The probe beam goes through the sample to35
a detector.13
Laser is an acronym for light amplification by
stimulated emission of radiation. A lasing medium is pumped into
an excited state through either heat or light. Some molecules
relax to a lower energy state to release a photon. As that photon
interacts with another electron in an excited phase it produces two40
photons of the same wavelength and phase. The process
continues and mirrors amplify these photons of the same
wavelength. These photons bounce back and forth two mirrors
placed on either side. Monochromatic, single phase light then
leaves through a half silvered mirror in a typical laser.14–17
45
This form of pump and probe spectroscopy is used to identify the
intermediates rhodopsin goes through after the excitation that
causes the photoisomerism reaction. Information regarding the
dynamics and mechanism of the initial cis-trans isomerism may
be obtained using such ultra-fast spectroscopic techniques.50
4. Speed and efficiency of process
It has been measured that the photoisomerisation is completed
and rhodopsin is converted to photorhodopsin within 200
femtoseconds (1 fs = 1×10-15
s).18,19
The process is extremely55
efficient as a human rod cell can respond to a single photon.
Furthermore recent studies suggest that isomerisation starts at 60
femtoseconds after the photon absorption and the isomerisation
occurs within 100 femtoseconds leading to the formation of a
twisted all-trans state in photorhodopsin within 20060
femtoseconds20
. Rhodopsin molecules that absorb a photon have
a 67% chance of being photoisomerised21
. It has been suggested
that the opsin protein attached to the retinal facilitates the
isomerisation to take place so efficiently. Studies have shown a
major difference in the efficiency and speed of the65
photoisomerism of retinal in solution and retinal in the opsin
protein environment present in the eye.22
5. Photoisomerisation
The photoisomerisation takes place through the excitation of70
electrons on the chromophore from the C11-C12 π bonding orbital
to the π anti-bonding orbital.23
This is accompanied by electron
density redistribution in the 11-cis-retinal.24
This leads to a
decrease in the energy barrier of torsional rotations around the
carbon11–carbon12 bond and leads to a cis to trans conversion,75
converting 11-cis-retinal to all-trans-retinal.4
The energy of the
transition is predicted to be about 2 eV.17,2
This
photoisomerisation leads to a process known as bleaching as after
going through intermediates, the rhodopsin splits into opsin and
retinal.25
This photoisomerisation leads to a change in the80
conformation of opsin and this triggers a chain of reactions within
the rhodopsin protein and causes the Rhodopsin to convert to
metarhodopsin-II through various recently discovered
intermediates. First of all rhodopsin is converted to
photorhodopsin within 200 femtoseconds then bathorhodopsin,85
lumirhodopsin, metarhodopsin-I and finally metarhodopsin-II.
Metarhodopsin-II is highly unstable and readily splits into opsin
and retinal units.23,26,27
The intermediates following
photoisomerisation have been discovered using Transient-
absorption spectroscopy within the femtosecond timeframe.90
Advances are currently being made to discover the mechanisms
that lead to the change in the structure of protein.
6. Electrical signals to the brain
Rhodopsin has an interaction with a G protein (proteins that95
transmit chemical signals) called transducin.28
Photoisomerisation
bleaches rhodopsin to form opsin. Opsin binds to transducin and
activates the protein. This leads to the rod outer membrane being
hyperpolarised, which stops the synaptic body from secreting
inhibitory neurotransmitters, thereby exciting bipolar neurons (a100
neuron that has two extensions) that they are connected to.23
This
leads to an action potential in the ganglion cells that send an
electrical signal through a long axon extending into the brain.28
This leads to human perception of light and a very similar
pathway applies to cone cells, which contain pigments that absorb105
different wavelengths of light. Cone cells differ by being less
sensitive to light than the rod cells and they have a faster response
time.25

3. This journal is © The Royal Society of Chemistry [year] Journal Name, [year], [vol], 00–00 | 3
Conclusion
We have discovered that rod cells work extremely efficiently and
quickly in detecting light and transmitting signals to the brain.
When light enters the eye, the process of transmitting the signal
to the brain starts occurring in the femtosecond timescale. The5
key process in perception of light is a cis to trans isomerisation.
The protein environment facilitates the isomerism to occur in an
incredibly small timescale with great efficiency. Recent advances
in ultrafast spectroscopy allow us to study in much more detail
how the protein structure can affect the photoisomerism process.10
In the year 2000, T. Okada successfully crystallised bovine
rhodopsin and further studies on this can help us better
understand the primary ultrafast reaction mechanism and
dynamics in rhodopsin.29–32
There is also scope for exploring how
mutations that occur around the chromophore binding pocket15
affect how photons are absorbed.24
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