Scientists solve mystery of the eye

Nov 17, 2011 by Lisa Zyga feature
A schematic representation of 7-cis- (PSB7, green), 9-cis- (PSB9, blue), 11-cis- (PSB11, black), 13-cis- (PSB13, purple), and all-trans-retinal (PSBT, red). PSB stands for “protonated Schiff base,” the linkage between the retinal chromophore and the opsin protein. Image credit: Sekharan and Morokuma. ©2011 American Chemical Society

(PhysOrg.com) -- Scientists have a good overall understanding of human vision: when light enters our eyes, it is focused by the lens and strikes the retina in the back of the eye. The light causes some of the millions of photoreceptor cells that line the retina to undergo a chemical change, which send a message through the optic nerve fiber to the brain, which creates a picture. However, there are still a few unresolved questions in the details of the vision process, one of which is why the eye evolved to use a certain light-absorbing chromophore called 11-cis-retinal instead of one of its isomers (i.e., molecules with the same atoms but in different arrangements), such as 7-cis, 9-cis, or 13-cis.

Chemists Sivakumar Sekharan from Emory University in Atlanta, Georgia, and Keiji Morokuma from Emory University and Kyoto University in Kyoto, Japan, describe the ’s use of 11-cis-retinal as “one of the basic and unresolved puzzles in the chemistry of vision.” But by taking advantage of the rapid advances in hybrid quantum mechanics/molecular mechanics (QM/MM) computational modeling, the researchers have found that the answer to this puzzle lies in electrostatic interactions in the retina. Their study is published in a recent issue of the Journal of the American Chemical Society.

The retina contains light-sensitive photoreceptor cells known as rods and cones, which convert incoming light into electrical impulses that are sent to the . On the top of every rod and cone is a region that contains opsin proteins bound to 11-cis-retinal chromophores, which together are called rhodopsin. When light strikes the retina, the 11-cis-retinal chromophores absorb the light, which causes them to undergo an isomerization and change their molecular configuration from 11-cis-retinal to all-trans-retinal in a matter of picoseconds. The difference between these two isomers involves the positions of the hydrogen , a shape change that causes the opsin protein to change shape in response. The opsin shape change, in turn, leads to a cascade of biochemical reactions in the photoreceptor cell that ultimately generate an electrical impulse.

Since the 11-cis-retinal is the ’s first responder to incoming light, its unique geometric configuration clearly plays an important role in the vision process. However, theoretically there are a handful of other retinal isomers that seem capable of performing this task, yet for some reason only function with 11-cis-retinal (and the corresponding 11-cis-rhodopsin).

“Because the primary event in vision involves no breaking of chemical bonds but only a conformational change in the shape of the molecule from bent cis to the distorted all-trans form, scientists wondered why 7-cis-, 9-cis- or 13-cis- isomers could not achieve this goal,” Sekharan told PhysOrg.com.

To answer this question, the researchers built computational models of the rhodopsin found in the eyes of cows, monkeys, and squids. While all known animals’ eyes use 11-cis-retinal, the opsin in different animals contains different numbers and positions of amino acids. Using a cutting-edge QM/MM modeling method called ONIOM (Our own N-layered Integrated Molecular Orbital), the researchers prepared models that matched different animals’ opsins with 7-cis, 9-cis, 11-cis, and 13-cis serving as chromophores. In these artificial rhodopsins, the researchers analyzed the structure, stability, energetics, and spectroscopy to try to find out what makes 11-cis-retinal nature’s preferred isomer.

The results of the modeling showed that differences in the electrostatic interactions between the opsin protein and the retinal chromophore played the biggest factor in the natural selection of 11-cis-retinal over the other cis isomers. Due to electric charges, the link between 11-cis-retinal and opsin has a higher stability than the links between other cis isomers and opsin, making it the most favorable choice.

“Our results show that the strong electrostatic interaction between retinal and opsin favors the natural selection of 11-cis- over other cis-isomers and arguably prepares the chromophore for the upcoming photochemical event,” Sekharan said. “This indeed is very surprising given the fact that, outside the protein environment, 11-cis-retinal is one of the least stable isomers. Apparently, our results on cow, monkey and squid demonstrate that organisms everywhere may tend to gravitate towards common selection.”

Sekharan added that the results not only provide a better understanding of the eyes on a molecular level, but could also have applications for artificial retinas.

“Because rhodopsin serves as a decisive crossing point between an organism and its environment, we have been always impressed with this interesting interface by seeing it, say, from the outside and not from the inside,” he said. “Using the ONIOM-QM/MM method we developed, we can ‘enter’ deep into the dark side of this fascinating molecule. One of interesting findings to emerge out of our investigation is that 9-cis-retinal is only slightly higher in energy compared to 11-cis-retinal. This provides strong evidence for the presence of 9-cis-rhodopsin in nature, which in turn may well aid in optimizing the parameters required for designing artificial retinas.”

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More information: Sivakumar Sekharan and Keiji Morokuma. “Why 11-cis-Retinal? Why Not 7-cis-, 9-cis-, or 13-cis-Retinal in the Eye?” Journal of the American Chemical Society. DOI:10.1021/ja208789h

Journal reference: Journal of the American Chemical Society search and more info website

4.3 /5 (71 votes)

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nanotech_republika_pl
5 / 5 (6) Nov 17, 2011
Well written report. Thanks.
Cynical1
5 / 5 (1) Nov 17, 2011
Agreed.
kevinrtrs
1.5 / 5 (15) Nov 25, 2011
there are still a few unresolved questions in the details of the vision process,

Presumably, all details of just HOW the eye evolved have been solved and now but a few loose ends remain to be tied up?
Here we have a molecule that's highly unstable outside of the protein environment, so just how did it "just happen" to develop anywhere in the first place? But of course since it is there and working, it MUST have evolved, otherwise we would be blind, right? And it just happens to be the most optimum solution out of a whole bunch of other choices, As i suspect they'll find out later, it's not the obvious choice since the others would have been easier to fall into place "by accident" and the 11-cis has to be delicately and precisely shoe-horned into its current place. But then, that's just how the designer chose to make it.

Cynical1
4.1 / 5 (8) Nov 25, 2011
As i suspect they'll find out later, it's not the obvious choice since the others would have been easier to fall into place "by accident" and the 11-cis has to be delicately and precisely shoe-horned into its current place. But then, that's just how the designer chose to make it.

The laws of possibility means tnat maybe it wasn't the FIRST choice. Perhaps evolution went thru NUMEROUS protein "experiments" before determining this one was the optimal. And who's to say it isn't done yet?
Cynical1
4 / 5 (8) Nov 25, 2011
Anyway. The Universe (along with everything else in it) designs itself via experimentation - ala evolution. No outside help needed.
Too many humans waste WAY too much time and energy on the 'who designed it' BS. If we expended that same energy on understanding WHAT was designed, the WHO would fall into our laps...
(BTW, it was US - the collective bundles of energy - that did it)
bewertow
4.5 / 5 (8) Nov 25, 2011
there are still a few unresolved questions in the details of the vision process,

Presumably, all details of just HOW the eye evolved have been solved and now but a few loose ends remain to be tied up?
Here we have a molecule that's highly unstable outside of the protein environment, so just how did it "just happen" to develop anywhere in the first place? But of course since it is there and working, it MUST have evolved, otherwise we would be blind, right? And it just happens to be the most optimum solution out of a whole bunch of other choices, As i suspect they'll find out later, it's not the obvious choice since the others would have been easier to fall into place "by accident" and the 11-cis has to be delicately and precisely shoe-horned into its current place. But then, that's just how the designer chose to make it.


What are you doing on a science website if you would rather believe in fairy tales than facts?
CHollman82
3.4 / 5 (5) Nov 29, 2011
Presumably, all details of just HOW the eye evolved have been solved and now but a few loose ends remain to be tied up?
Here we have a molecule that's highly unstable outside of the protein environment, so just how did it "just happen" to develop anywhere in the first place? But of course since it is there and working, it MUST have evolved, otherwise we would be blind, right?


What's the alternative kevin, that your god designed the eye? If he did he is an idiot, because my eyes and the eyes of most of my family members are complete shit. Most of us can't see our own hand in front of our face without glasses or contacts.

Good job God, nice handiwork.

Evolution does not guarantee a good design, just the best one so far.
Crucialitis
1 / 5 (2) Nov 29, 2011
God is running an experiment upon itself.

Everyone wins.
CHollman82
1 / 5 (1) Nov 30, 2011
God is running an experiment upon itself.

Everyone wins.


God is supposed to be a supreme omni* being, something of that nature does not need to run experiments. What you have said only makes sense if you consider "god" to just be an alien.
A_Paradox
1 / 5 (1) Nov 30, 2011
On the top of every rod and cone is a region that contains opsin proteins bound to 11-cis-retinal chromophores, which together are called rhodopsin. When light strikes the retina, the 11-cis-retinal chromophores absorb the light, which causes them to undergo an isomerization and change their molecular configuration from 11-cis-retinal to all-trans-retinal in a matter of picoseconds.


OK, so I'm missing something here: "light strikes the retina" tells me nothing about how or if this molecular arrangement distinguishes between frequencies of light. So, while this article is very interesting, what is the answer to *my* question?
kevinrtrs
1 / 5 (5) Dec 05, 2011
because my eyes and the eyes of most of my family members are complete shit

Dear CHollman82,
God designed the eyes to perfection for Adam and Eve. BUT when sin entered, the whole of creation was cursed and made subject to decay and ultimately death. This is why we have disease and one of the diseases is that your eyes are not repaired in optimal manner any more. THAT's why you and most of your family and friends have to wear some kind of accessory to help them see properly.
The eyes were designed. They could not and did not evolve. Simply impossible for probably the most sophisticated optical transducer ever known to man to "just happen". Try finding any man-made computing engine that does 3-d Fourier transforms at such speed using such little power,space and precision. AND repairs itself simultaneously. Doesn't exist.
kevinrtrs
1 / 5 (5) Dec 05, 2011
What are you doing on a science website if you would rather believe in fairy tales than facts?

Perhaps you should ask yourself that question?
If you really start to put your mind to it and ask really hard questions about just HOW the eye could have evolved you will begin to SEE just how impossible that could be. Take the eye apart bit by bit and ask how each of those pieces could ever have arrived by chance. Look especially at the energy required for each kind of bond to take place in "trying" out new molecular constructions to give just the right kind of material for light sensitivity. Then just the right kind of material for constructing a nerve. Then just the right kind of material to construct the optical channels that transfer light through the wall of blood vessels that nourish and cool the optical nerve system. Oh, and how come those blood vessels just happened to be in the right place and of the right size to supply the right kind of nutrients to the right place? THINK
FrankHerbert
1.5 / 5 (8) Dec 05, 2011
Human eyes aren't just subject to "decay and ultimately death" they are the product of bad engineering.

If the eye really was created by God, and as a result of Original Sin, our eyes were allowed to become defective, it's not as simple as God just flipping the entropy switch.

If that really is the case, God actually would have changed the structure of the eye itself. Our are are poorly designed compared to other examples. The only logical explanation for the poor design of our eyes is that NO ONE designed them. They just happen to work well enough.

So to sum up: it's the creationist position that upon original sin our bodies were allowed to deteriorate. However, our eyes are not subject just to deterioration, but are the product of bad design. So if true, god didn't simply allow them to go bad with age, but he actually changed the physical structure of the eye to a much poorer design.

I guess Adam and Eve had mantis shrimp eyes prior to The Fall.
CHollman82
3 / 5 (2) Dec 05, 2011
Kevin,

You do realize that not all animals have the same type of eyes as humans right? I believe it is mollusks for example (don't hold me to that I am trying to remember biology from a decade ago) that have merely a small collection of light sensitive cells at the back of an indented cavity that serves as their visual perception. This provides them with little more than the ability to discern light from darkness and to see silhouettes. There are even more primitive examples but you can research them on your own. From these simple collections of light sensitive cells up to the modern eyes of humans or eagles or whatever there are iterative developmental steps that are CLEARLY expressed in the animal kingdom RIGHT NOW.

To ignore this and to proclaim that they eye "couldn't possibly have evolved" is, quite simply, lunacy.