New Tool For Studying Vision, Eye Disease
The tiny eyeless C. elegans roundworm, one of the most widely used animals in biological research, can detect flashes of light and responds to them by quickly wriggling away, a University of Michigan biologist and his colleagues have discovered.
The finding should lead to an expanded research role for C. elegans, already one of the mainstay model organisms of biology, said Shawn Xu, a research assistant professor at the U-M's Life Sciences Institute.
"Though this animal lacks the specialized light-sensing organs we call eyes, it can still see light," said Xu, also an assistant professor of molecular and integrative physiology at the U-M medical school. "We now have a new model that can be used to study the building blocks of the visual system and the causes of human eye diseases."
Researchers have long assumed that the soil-dwelling worm, about the size of this comma, lacks any visual system whatsoever. After all, it is eyeless and spends its entire life in the dark, so why would it need vision?
Xu suspects the worm's primitive visual system serves a protective function. It tells the worm when it is nearing the surface, enabling it to avoid damaging sunlight. Ultraviolet-A radiation in sunlight is harmful to C. elegans worms, and prolonged exposure to it kills them.
"They see the light and don't like it, and the light drives them back into a dark environment," Xu said.
The new C. elegans finding suggests that other eyeless animals living in dark environments, such as soil or caves, also can sense light, he said.
Xu and his colleagues found that humans and the C. elegans worm rely on many of the same chemical reactions to convert light energy into electrical signals, a process called phototransduction. That means the worm can be used to study the building blocks of human vision, as well as how disrupting the phototransduction pathway can lead to eye disease.
The Xu team's findings will be published online July 6 in Nature Neuroscience. Co-lead authors of the paper are Alex Ward and Jie Liu of the U-M Life Sciences Institute.
In addition to demonstrating that C. elegans can detect and respond to light flashes, Xu's team suggests that the worm's primitive light-sensing system has the properties of the primordial eye proposed by Charles Darwin in "The Origin of Species."
The eye is one of the most complex structures in nature, and its design varies greatly across the animal kingdom. The fruit fly's compound eye, made of 800 linked mini-eyes, looks nothing like the single-lensed human eye, for example.
Eye evolution has been the subject of extensive study, and researchers fall into two camps. One group holds that because animal eyes are so diverse, nature must have invented multiple visual systems throughout evolutionary history.
Scientists in the other camp suspect that all modern eyes evolved from a single prototype. In 1859, Darwin advanced the idea of a primordial eye that contained just two cells: a light-sensitive photoreceptor and a pigment cell that shielded the photoreceptor, enabling the organism to determine the direction of a light source.
C. elegans has photoreceptors but lacks pigment cells. However, soil may substitute for the missing pigment cells: The dirt prevents light from striking the photoreceptors, except when the worm nears the surface.
"We're suggesting that the photoreceptor cells we've discovered in C. elegans resemble Darwin's primitive eye—the prototype for all visual systems—and that this system has been preserved over the course of several hundred million years of evolution," Xu said.
Since the 1970s, the C. elegans roundworm has been used to study the genetic control of animal development, as well as sensory physiology. Because it is one of the simplest organisms with a nervous system (302 nerve cells versus about 100 billion in the human brain), it is widely used to probe the neural mechanisms behind various behaviors.
In their experiments, Xu and his colleagues directed a tightly focused light beam at the heads or tails of C. elegans worms under a microscope. When pulses of light struck the head of a forward-moving worm, it stopped and reversed course. When light was aimed at the tail of a backward-moving worm, it switched gears and began inching forward.
Scientists call this type of light-avoidance response a negative phototaxis. The stronges response was observed when ultraviolet-A light, the component of sunlight responsible for tanning in humans, was used.
"We were very surprised and excited to discover that this 1-millimeter-long worm can sense light and respond to it. We all thought they ought to be light-insensitive," said Liu, a research fellow at the Life Sciences Institute.
Xu's team used lasers to systematically knock out various types of nerve cells in the worms. Then the worms were exposed to UV-A light, and their response was observed.
By determining which nerve cells were required to elicit a light-avoidance response, they were able to identify four types of nerve cells as candidate photoreceptors: ASJ, AWB, ASK and ASH. Other types of cells may also be involved.
Scientists have known for years that the rudimentary C. elegans nervous system provides the worm with the senses of touch, taste and smell. Two years ago, the Xu lab—which studies C. elegans full time—reported in the journal Nature that the worms possess a fourth sense, an awareness of body posture known as proprioception.
"Now we've added a fifth sense: the ability to sense light," Xu said.