Gene Needed for Vision Identified

A gene that is needed for the eye to see rapidly moving objects has been identified in mice. The discovery gives researchers a new tool for studying hereditary vision defects in humans.

Scientists at Baylor College of Medicine, Stanford University Medical Center in Stanford, Calif., and California Institute of Technology in Pasadena report their findings in the Feb. 3 issue of the journal Nature.

A gene called RGS9-1 turns off the nerve cells in the retina after they have been activated by light energy. This process enables these photoreceptor cells to return to a dark state so they can be re-activated by more light energy. The rapid rate at which the cells respond to these changes is what makes vision of moving objects possible. Thanks to RGS9-1, the eye can track a baseball travelling faster than 90 miles per hour.

The RGS9-1 gene was discovered in 1998 in the lab of Dr. Theodore Wensel at Baylor, but its function wasn't proven until now.

Scientists at Caltech created a mouse in which the RGS9-1 gene had been knocked out, or turned off. Without the gene, the mouse could not process rapid changes in light. Retinal cells that normally turn off in less than one second remained activated for more than 20 seconds.

Dr. Wensel's group conducted the biochemical analysis explaining the changes that occurred.

"The chain reaction of cellular response triggered by light activation uses a type of communication between cells called G-protein-coupled signaling," says Dr. Wensel, Baylor professor of biochemistry and molecular biology and ophthalmology. "In fact, this type of signaling is used not just in the retina, but also throughout the body. It is the most common way that our cells respond to hormones, nerve transmitters and other stimuli, including drugs."

After Dr. Wensel discovered the RGS9-1, he determined that a protein in photoreceptor cells could accelerate how fast the G-protein signaling was turned off. Over the past several years, researchers found similar forms of the RGS (regulators of G-protein signaling) protein and suspected their function might be to turn off the communication.

"The study published in Nature is the first proof in animals that the RGS family of proteins stops the signaling," Dr. Wensel says.

His lab is now studying the role of these genes and proteins in human disease. Mutations in other genes that play a role in controlling signaling in photoreceptor cells are known to cause hereditary visual defects such as the eye disease retinitis pigmentosa. DNA from patients with this disease is being screened at other institutions to determine whether their RGS9-1 genes are involved.

The research on RGS has the potential to learn more about cellular response in other parts of the body.

"Understanding the roles of RGS proteins in pathways involved in drug responses and control of hormones might lead to new approaches to highly selective therapies for a wide range of diseases," Dr. Wensel says. His Baylor co-author was Dr. Wei He, a graduate student in biochemistry and molecular biology. The National Eye Institute and the Welch Foundation supported the research.

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©2006 Texas Medical Center

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