Seeing the Light

13 August 2014

Interview with

Prof Rob Lucas, Manchester University

Poets may claim our eyes are the windows to the soul, but to scientists they're an important way of sensing the world around us by detecting light - or seeing, as we usually call it. To find out more about how organisms, including humans, detect light - through special cells called photoreceptors - Kat Arney spoke to Rob Lucas, professor of neurobiology at Manchester University.

Rob -   There are lots of different mechanisms that organisms use to sense light.  Probably because it's going to be amongst the oldest sensory systems that organisms evolve.  But if we concentrate on animals and particularly on vertebrates then there is a particular class of proteins called opsins that they use to detect light.  And these are proteins that bind a derivative of vitamin A called retinaldehyde.  It's actually that retinaldehyde that absorbs the light and the opsin protein has the really clever job of detecting that light absorption and setting in chain a biological response.  The rods and cones are packed full of opsins that are used to absorb light. 

Until about 10, 15 years ago, it was assumed that they were the only cells in the retina that contained opsin and they were the only cells therefore that were capable of responding to light.  And so, that's still the major way in which mammals detect light.  But we've been interested in this new sort of cell type in the retina that also contains opsins and we've discovered them about a decade ago or something like that.

Kat -   How did you find these?

Rob -   So, that was work not just from my own lab, but from various labs around the world.  My own contribution to it when I was working as a post doc in Russell Foster's lab, we generated mice that lacked rod and cone photoreceptors and therefore, by all rights should have been completely blind.  But it showed that they still had some light responses and that implied that there was something else in the retina capable of responding to light. 

And then a scientist at Brown University in the US called David Berson recorded electrophysiologically from some of the retinal ganglion cells, these are the cells that form the optic nerve, and showed that they were capable of responding directly to light.  That was first description of this new photoreceptor.

Kat -   That must've been incredible to think that there was something as fundamental as the eye and there's this whole extra layer that we never knew about.

Rob -   Yeah, it's been really, really exciting and certainly, at the time when I started working in this field, there was huge reluctance from vision scientists to countenance the idea that they might have missed something.  In a way, it's quite a nice illustration of general themes I think in biology going forward and that is, that the more you look at things in detail, the more you find rare events that are nonetheless really, really important. 

So, this sort of photoreceptor in human retina, there might be about a thousand of these photoreceptor cells compared to many millions of rods and cones.  So, if you were to just - as a first approximation, say, where does photoreception occur in the mammalian retina?  The answer is in rods and cones.  But that's not to say it doesn't also occur elsewhere.  Just because there were so few of these other cells doesn't mean they aren't important for us.  So, there's a lot to be discovered by looking at rare events.

Kat -   And of course, this begs the question, what are they doing there?

Rob -   Why are they important?  Our knowledge of that is really developing but their really widely accepted roles to provide our brain with a signal of the overall amounts of light there is in the environment.  So, why do we need that?  The most obvious answer to our question is that we use it to adjust our physiology and behaviour according to time of day.  And so, we used the output of these cells to synchronise our biological clocks, time of day.  So, when you fly to New York, its light has detected by these new photoreceptors which tells you that it's daytime when you're expecting it to be night and therefore adjust your clock.  But also, there are direct effects of light.  There are alerting effects of light and this come probably mainly from these retinal ganglion cells.

Kat -   Waking you up.

Rob -   Yeah, waking you up, increasing your body temperature, changing hormone levels - from that to very simple reflex responses.  So, for example, the pupil light reflex.  Many people will be aware that when the light is bright, your pupil is small.  All that's down to these ganglion cells as well.

Kat -   And what do we know about the way that these unusual photoreceptors are working?  Do they have similar molecules in them to the rods and cones?

Rob -   They also use opsins, but it's a particular sort of opsin.  It's an opsin called melanopsin.  It's called melanopsin because it was first discovered in the dermal melanophores.  So, these are the skin pigment cells of amphibia.  And so, it's involved in changing skin pigmentation in amphibia, depending on light intensity.  And it's this opsin which has been involved in those skin cells of toads and frogs that is then also present in our eyes and we use to detect light.

Kat -   How widely across the animal kingdom do you find these unusual opsins and are they always used for detecting general levels of light and then doing something in response?

Rob -   So, it turns out that actually, mammals are unusually boring in terms of the range of opsins that we have.  So, we have in addition to our rod and cone opsins, we have melanopsin.  We use that as I've described.  If you look outside mammals and other vertebrates, they have melanopsin, they have rod and cone opsin, they also have lots of other sorts of opsins that they use for exactly this purpose.  And very commonly, those opsins would be found in places other than the eyes.  So, we talked about the amphibian skin, but also, deep within the brain of many of these other animals, they have photoreceptors which means that if you were to remove their eyes for example, they would still synchronise biological clocks to local times, still adjust their behaviour according to light dark cycles.

Kat -   That's like some freaky third eye!

Rob -   Yes, so the third eye, parietal eye in lizards is obviously photoreceptor but then they also have pineal glands which we have a pineal but it's not photosensitive.  But in these other organisms, it is photosensitive.  The more that you dig around in these guys, the more you find light sensitivity to the extent that if you take for example a fish heart and put it in a culture dish, you can get it to respond to light.

Kat -   Why on earth are they so widespread then through evolution?

Rob -   One of the first pieces of advice I had when starting studying biology is never ask a 'why' question because we can never know the answer.  But I'm going to answer it anyway.  Of course, it's complete speculation.  The question of why they're so widespread, I guess the answer to that must be that this light information is valuable for lots in different parts of our bodies, right?  So, the fact that you have photoreceptors in the heart is because the sort of level of activity you have in the day and night is different.  And so, it's useful for the heart to know what time of day it is.  If we can do that by having its own light measurement system, why wouldn't it?

Kat -   At least if you're a fish.

Rob -   At least if you're a fish.  But even if you were a mammal, why is that not the case also for a mammal?  So obviously, there are lots of small mammals that light would penetrate their body just fine.  And so, you can break it down into those related questions, why is it valuable for a fish let's say, and why isn't it valuable for a mammal?  And I think we can say what might be valuable for a fish. Why it's not valuable for a mammal, it's harder to answer.  The current best guess on that is that actually, it's a reflection of our evolutionary history. 

So, mammals, as far as one can tell would nocturnal for tens of millions of years of our evolution.  When they're nocturnal, there's not much light around to be exposed to.  As a result, lots of these light-sensitive proteins are lost because the light doesn't reach the heart of a nocturnal animal as much as it would for a diurnal animal for example.  And so, lots of those photoreceptors were lost and that's why we don't have them now even though many mammalian species could if they wanted to have photoreceptors outside the eyes.

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