Fly Eyes Provide a Clue to Vision

For seven years, San Diego biologist Charles S. Zuker has looked into the tiny eyes of mutant fruit flies, trying to better understand sight in the hope of one day preventing blindness.

According to a report published today, Zuker and a team of researchers at UC San Diego have identified a protein that plays a key role in regulating and protecting the light-sensitive cells of the retina--a discovery that could eventually help scientists stave off degenerative human eye disorders that can lead to blindness.

Zuker, an associate professor of biology at UCSD, believes the results of his work with fruit flies will accelerate the search for the protein performing the same function in the human eye.

“I would be extremely surprised if a comparable protein were not found in the visual system of humans,” he said. “So far, there have been many common components between flies and humans. Once you know a molecule is expected to exist there, you can go look for it, and the technology is there to do it reasonably fast.”

If scientists could determine the protein in the human retina, they might be able to prevent disorders such as retinitis pigmentosa, a family of disorders in which the photoreceptor cells degenerate, sometimes resulting in blindness. The disorder affects about one in 4,000 people, said Zuker, who is also an investigator with the Howard Hughes Medical Institute at UCSD.

Several experts agreed that the findings, published in today’s issue of Science, could have valuable applications.

“It’s very important work. It gives clues of what to look for in the human retina when it doesn’t function properly,” said Deborah Farber, a professor of ophthalmology at UCLA’s Jules Stein Eye Institute.

“It doesn’t necessarily follow that, because this is key in fruit flies, that it will have the same role in humans. But the more we understand at this molecular level, it’s bound to help us understand comparable things in humans,” said Simon LeVay, an associate professor specializing in visual research at the Salk Institute.

To study how the eye sees at a molecular level, Zuker used fruit flies because they reproduce quickly and their genes are easily mutated and reintroduced to determine how their vision is altered. But there are key differences between human and fly eyes: Flies have compound eyes, composed of 800 smaller eyes.

Zuker and his team used several biochemical and electrical tools to monitor the fly eyes, including “patch clamping,” a revolutionary technique for recording electrical changes in cells that won a Nobel Prize for its inventors in October.

With this monitoring, UCSD scientists determined that mutant flies that lacked protein kinase C, or eye-PKC, had abnormal vision, indicated by their photoreceptors reacting strangely when light was turned on and off. This enabled the scientists to realize their theory: The protein kinase C regulates and protects the retina’s light-sensitive cells by acting as an on-off switch, affecting a cascade of reactions that result in vision.

When kinase C was reintroduced to the mutant fruit flies, normal vision was restored.

“Our ability to see properly depends to a great extent on the ability to regulate the signal process properly,” Zuker said. “If you don’t regulate it properly, you can have multiple outcomes--cells won’t be able to deal with mis-regulation and eventually die. When they die, there’s retinal degeneration.”

In humans, a similar mechanism in the retina regulates the way cells respond to light stimulus, Zuker said, but this mechanism has yet to be pinpointed.

The process of human vision is complicated. A person is able to see because light activates cells in the retina; once activated, these cells undergo a series of biochemical events that fire an electrical signal to the brain. This signal is then analyzed and processed--resulting in the image actually seen. The process takes a couple of hundred milliseconds, which is why, for instance, you can’t see a fast ball as it’s thrown by a pitcher and instead see a blur of movement.

Zuker’s UCSD colleagues on the research were Dean P. Smith, Rama Ranganathan, Robert W. Hardy, Julia Marx and Tammy Tsuchida.