Cross-breeding restores sight to blind cavefish

Blogging on Peer-Reviewed ResearchIn the caves of Mexico lives a fish which proves that a million years of evolution can be undone with a bit of clever breeding.

Blind cavefishThe blind cavefish (Astyanax mexicanus) is a sightless version of a popular aquarium species, the Mexican tetra. They live in 29 deep caves scattered throughout Mexico, which their sighted ancestors colonised in the middle of the Pleistocene era. In this environment of perpetual darkness, the eyes of these forerunners were of little use and as generations passed, they disappeared entirely. They now navigate through the pitch-blackness by using their lateral lines to sense changes in water pressure.

But there is a deceptively simple way of restoring both the eyes and sight that evolution has taken, and Richard Borowsky from New York University’s Cave Biology Research Group has found it. You merely cross-bred fish from different caves.

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Living optic fibres bypass the retina’s back-to-front structure

The human retina is back-to-front. Its silly structure means that light has to cross a tangle of nerves and blood vessels before it reaches the light sensors at the back. Now, scientists have found that the retina uses special cells called Muller cells that funnel light through the retina, in the style of living optic fibres.

If you were a designer tasked with creating a machine for collecting and processing light, the last thing you would come up with is the human eye. Darwin marvelled at the eye’s perfection, but in this, he was wrong. Aside from the many illusions that can fool it, our eyes have a major structural flaw.

The human retina is back-to-front and has the light sensing cells at the back.In humans and other back-boned animals, the light-sensing cells of the eye lie at the back of the retina (see image right; courtesy of University of Michigan).

In front of these sensors lie several layers of nerve cells that carry their signals, and blood vessels that supply them with nutrients. The nerves join to the main optic nerve which passes through a hole in the centre of the retina and connects to the brain.

It’s a stupid, back-to-front design. Light has to pass through several layers of nerves, not to mention blood vessels, before it hits the retina itself. It’s a bit like designing a camera, and sticking the wiring in front of the lens.

Octopuses and squid have a very similar eye to ours, but theirs’ are much more sensibly structured. Their nerves and blood vessels connect to the light sensors from behind so that light can hit the sensor cells without having to negotiate an obstacle course. And because their retina doesn’t need a hole to accommodate the optic nerve, they have no blind spot.

In our own retinas, nerves and vessels are random in their spacing and irregular in their shape. The light that shines past them is reflected, scattered and refracted.

It’s amazing that our eye can see at all. But even though there is clearly no designer, evolution does a pretty good job instead. It has a remarkable capacity for making the best of a bad job. In the case of our eye, some of the obscuring cells act as living optic fibres, to funnel light onto the sensors it covers.

Muller cells – living optic fibres

Muller cells behave like optic fibres.Kristian Franke and colleagues from the Paul Flechsig Institute for Brain Research first noticed these fibres by shining light onto the retinas of guinea pigs. They looked at a cross-section near where the light sensors lay and saw a very regular pattern of bright spots. Clearly, some parts of the retina were transmitting light far better than others.

As they looked at further cross-sections throughout the retina, they realised that the bright spots were the endpoints of long tubes that stretched throughout the retina. Near the top, the tubes widened into funnels.

Franze identified these tubes as Muller cells. The brain cells aren’t nerves themselves, but are part of their supporting cast. They are long cylinders arranged in columns across the entire retina, and provide a route for light to pass through the tangled morass of nerves and blood vessels.

How they work

The eye has evolved to produce images despite a silly back-to-front retina.The Muller cells gather light at the top of the retina and channel it to the light sensors as a tight beam. Along the way, the light is barely reflected or scattered and little is lost when it finally reaches the light sensors, just like modern optic fibres.

Light enters the Muller cells at a shallow angle and is slowed down considerably by the cells’ high refractive index. When it hits the cells’ boundaries, it is almost completely reflected back along the tube.

Their funnel shape allows the Muller cells to gather and transmit as much light as possible. But as they narrow in the middle, they take up a very small amount of space and leave plenty of room for the blood vessels and nerves that the retina needs.

On average, each Muller cell serves a single cone cell and several rod cells. This one-to-one system ensures that the images that eventually hit the light sensors keep strong contrast, and are not distorted.

Evolution has given the vertebrate eye a remarkably ingenious solution to its ludicrous inverted retina. The eye may not be the perfect organ that Darwin thought, but new insights into its’ evolution still provides us with awe-inspiring surprises.


Reference: Franze, Grosche, Skatchkov, Schinkinger, Foja, Schild, Uckermann, Travis, Reichenbach & Guck. 2007. Muller cells are living optical fibers in the vertebrate retina. PNAS 104: 8287-8292.

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Human cone cell lets mice see in new colours

While humans have three types of colour-detecting cells, mice and most other mammals have just two. But when a group of scientists gave mice the human gene for a third colour detector, they were able to detect colours that no mouse has ever seen before. This profound response to a simple genetic change may show us how our own vision evolved.

A new human receptor gives mice the ability to see into the orange and red end of the spectrumEvolution is almost synonymous with small, gradual changes, and for good reason. We might expect that large changes to an animal’s genetic code, and therefore to its body plan, simply wouldn’t work. It would be like shoving an extra cog into a finely-tuned machine and expecting it to fit in – the more likely outcome is a malfunctioning mess.

But that’s not always the case, at least not for the evolution of the human eye. To Darwin, the eye was so perfect that it made him cast serious doubts over his theory of evolution.

But new research shows that the eye and its connections to the brain are surprisingly flexible, and can incorporate major evolutionary changes with ease.

In our retinas, cone cells are responsible for giving us colour vision. Most mammals have just two types, one that is sensitive to short violet-ish wavelengths of light (S cones), and another that responds strongly to medium greenish-blue wavelengths (M cones).

But somewhere in our history, humans and many other primates picked up a third cone sensitive to longer wavelengths (L cones), that allows us to see colours near the red end of the spectrum.

You might expect that adding another type of cone cell into the eye would be a very large step, requiring substantial (and gradual) changes in the wiring of both the retina and the brain. But Gerald Jacobs from the University of California has shown that it’s as easy as installing new software into your computer.

The three human cone cells respond to different wavelengths of light.Together with Jeremy Nathans from Johns Hopkins Medical School, Jacobs genetically engineered a strain of mice that had human L cones in addition to its medium and short-wavelength ones.

Using a technique called electroretinography, they confirmed that these added cones were in full working order and were sending electrical outputs to the brain. They were clearly providing visual signals, but did this translate into any meaningful information in their brains?

Nathans and Jacobs set the mice a challenge to test their new retinal powers. They were shown three panels lit with coloured lights and had to pick out the one that was lit differently.

The normal mice failed to tell the difference between greenish-blue and yellowy-orange lights. They only chose correctly about a third of the time – the success rate you’d expect from random guesswork.

But the triple-coned mice passed with flying colours, so to speak. After lengthy training, they picked the odd panel out up to 80% of the time. Their genetic change had clearly been smoothly slotted in to their nervous system. They were seeing in three colours.

The human eye has three types of colour-detecting cone cells.The success of Nathans’s experiment is testament to the tremendous flexibility of a mammal’s nervous system. And it gives us a tantalising glimpse into how modern primate vision evolved.

At some point in our evolutionary past, one of our ancestors was born with a mutation that gave it a third and slightly different type of cone cell. This change would have brought it an instantaneous competitive edge over its two-coned peers.

Having three types of cones, rather than two, greatly expands the range of light that an animal can detect, and gives it a much broader colour palette. Such an animal would have gained a deeper appreciation of its surroundings than its peers – its eyes would quite literally have been opened to new possibilities.

Some scientists believes that the key advantage lay in being able to discern unripe green fruit from ripe ones that are typically red or orange. The bright colours of fruit may even have co-evolved with the advent of three-coned primate vision, to take advantage of these new seed-dispersing agents.

Over future generations, these new visual powers would have been honed by further genetic changes, but it is highly likely that the initial genetic jump-start would have spread like evolutionary wildfire.

The same may even apply to other senses, like taste and smell, with new genetic changes caused profound effects by adding new receptors and expanding an animal’s sensory range.

Reference: Jacobs, Williams, Cahill & Nathans. 2006. Emergence of novel colour vision in mice engineered to express a human cone photopigment. Science 315: 1723-1725.

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