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Health Center research team finds path to vision loss

by Chris DeFrancesco - September 10, 2007

A research team led by Timothy Hla, director of the Center for Vascular Biology at the UConn Health Center, has found a molecule in blood plasma that may hold one of the keys to vision loss.

The discovery could ultimately lead to the development of a way to treat and prevent blindness.

Central to the research of Hla and graduate assistant Athanasia Skoura, which is published in the September 2007 issue of the Journal of Clinical Investigation, are blood vessels in the retina and a lipid molecule called sphingosine 1-phosphate, or S1P.

“We studied a specific receptor that binds to sphingosine 1-phosphate and showed it is essential for the proliferation of abnormal blood vessels in mice,” Hla says.

“These abnormalities often lead to blindness in people with diabetes or age-related macular degeneration.”

Diabetes and macular degeneration can damage the retina, through low oxygen levels.

The conditions then are right for the development of a network of vision-robbing blood vessels.

But when Hla and Skoura took S1P receptor-2 out of the equation, the outcome was very different.

The mice bred without it experienced normal blood vessel growth in the retina, which is essential for healthy eyesight.

“We wanted to study the role of the S1P receptor-2 in retina vascular development of the mouse because it’s a nice model to compare to human disease,” Skoura says.

“We found that the receptor enhances pathological mouse retinal angiogenesis.”

Adds Hla, “This is the first time this molecule has been connected with blood vessel abnormalities in mice.”

Skoura says it may be possible to design a molecule-antagonist that will specifically target the receptor, inhibiting its function while sparing healthy tissue and therefore avoiding harmful side effects.

Timothy Hla, director of the Center for Vascular Biology, speaks with research colleagues in a lab at the UConn Health Center.
Timothy Hla, director of the Center for Vascular Biology, speaks with research colleagues in a lab at the UConn Health Center.
Photo by Al Ferreira

Two drugs currently on the market have been shown to inhibit the growth of abnormal blood vessels and in some cases actually improve the vision of the macular degeneration sufferer.

If Hla and Skoura’s research translates to humans, drug therapies could address the problem earlier in the process, focusing instead on what makes the blood vessels abnormal in the first place.

“Our study suggests that drugs or therapies that inhibit S1P receptor-2 could be useful in the treatment of blood vessel abnormalities in the retina that lead to blindness,” Hla says.

What remains unclear is why the body produces S1P receptor-2. This research suggests it also controls inflammation and blood vessel leakage.

Skoura says the research was a big part of her thesis project. She and Hla starting working on it three years ago.

The JCI is a free access, peer-reviewed biomedical research journal. It is published by the American Society for Clinical Investigation, an honor society of physician-scientists. Research appearing in the September issue, including this study, is available online at www.jci.org.

A patent application has been filed on the discovery by UConn’s Center for Science and Technology Commercialization.

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