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Discovery by University of Utah may prevent blindness

SHARE Discovery by University of Utah may prevent blindness

University of Utah researchers have found that activating a protein

that stabilizes blood vessels reverses diabetic retinopathy and

age-related macular degeneration — two common causes of blindness.

They believe the treatment, which they tested in mice, may

portend good news for many other diseases as well that occur or worsen

because of vascular instability and leaky vessels.

The study, which involved several institutions, was published Sunday in Nature Medicine online.

While the research is several years from human use, the director

of the U.'s John A. Moran Eye Center, Dr. Randall J. Olson, called the

finding "historic" in a release about the study. Hemin Chin, director

of ocular genetics at the National Eye Institute, termed it "a major

scientific advancement."

"All major eye diseases are caused by blood vessels that are

destabilized such that they leak or grow too much," said Dr. Dean Li,

the study's senior author, who is a physician, geneticist and professor

of internal medicine at the U. "The two major eye diseases that affect

the United States are diabetic eye disease and age-related macular

degeneration (AMD). The vessels start falling apart, leaking and

bleeding, and cause you to go blind."The newly discovered pathway antagonizes that process and the vessels

stabilize, offering hope for treatment, prevention and possibly a cure.

Researchers activated a protein called Robo4 in mice in which

they had simulated the eye diseases. The Robo4 stopped abnormal blood

vessel growth and stabilized the vessels so they wouldn't leak — the

primary causes of both types of eye disease.

Robo4 is found only in cells on the inside surface of blood

vessels. When a protein called slit activates it, the process begins to

stop leakage and inhibit undesirable growth.

Blood vessels have a receptor on the cell surface, and there are

proteins that bind to it. By turning on a signal in the endothelium, Li

said, "we tell the vessels to have a stable structure, to have good

interactions with other cells so they don't leak." They've shown "proof

of principle" in the eye with "well-worked-out models."

Many other illnesses also spring from or are greatly worsened by

blood vessel instability and leakage. With SARS or influenza, for

instance, infection causes unstable blood vessels to leak fluid into

the lungs. Blood vessels are also central to tumors, which feed off

blood vessels. Whether turning on Robo4 would treat those and other

ills is unknown, but Li is hopeful.

"What our discovery does has direct application to eye disease

and diabetes and age-related macular degeneration. But most everyone is

familiar with the bad effects of vessel destabilization. We think any

disease where vessels leak and accumulate could benefit. How broad is

this principle and how strong the application outside of the eye, we

don't yet know."

Dr. Kang Zhang, associate professor of ophthalmology and visual

sciences at the Moran Eye Center and an investigator with the U.'s

Program in Human Molecular Biology and Genetics, touted the potential

for developing drugs to activate Robo4. His lab worked with Li's, using

the same eye disease animal models used for drug development, which

could shorten the time it takes to get to human trials.

Like other treatments that affect an eye's blood vessels, this is injected, Li said.

He predicts an eventual "race to figure out how to make something

smaller to activate this receptor so we can do it without injecting."

Some treatments exist for AMD, the leading cause of blindness in people

over 65, he said. For diabetic eye disease (the leading cause in

younger adults), there are no proven therapies.

Li left the biotech field for academia five years ago

specifically to research eye blood vessel instability and ways to

reverse it. His U. collaborators on the study include graduate student

Christopher A. Jones and Nyall London, an M.D./Ph.D. candidate in the

Department of Oncological Sciences and the Program in Human Molecular

Biology and Genetics, as well as several other researchers from Li's

lab. Others contributed from the University of California, San Diego;

the National Heart, Lung and Blood Institute; and Harvard Medical

School. Much of the funding came from the National Heart, Lung and

Blood Institute and the National Eye Institute.