As reported by the New Haven Register, August 20, 2007.

UConn Finds Odd Molecule May Curb Eyesight, Hearing Loss

By Abram Katz

An unusual molecule in blood plasma might hold the key to treating two common forms of blindness, and may even help hearing, according to research by a scientist at the University of Connecticut Health Center.

The retina in the back of the eye and the inner ear both require unhindered blood supplies.

Patients with diabetes are prone to a condition called diabetic retinopathy. A tangle of leaky vessels grows over the sensitive tissue of nerves that transports vision to the brain. Eventually, sight may be lost.

Age-related macular degeneration, one of the major causes of blindness, involves a similar growth of obstructing vessels.

Timothy Hla, director of the Center for Vascular Biology at the University of Connecticut Health Center, apparently has identified a main culprit in both disorders.

It's a small molecule of lipids and growth factors circulating in the blood stream called sphingosine phosphate, abbreviated as S1P.

S1P regulates blood vessel growth by acting through five different receptors that are good targets for future drugs.

What's odd about S1P is that it only seems to cause trouble.

Normal vessel function is essential to a healthy retina. The retina is a small patch of brain tissue that requires a good blood supply, Hla said. The eyes of diabetics often suffer retinal vessel damage.

Abnormal vessels then form in response. The vessels leak and grow uncontrollably, eventually detaching the retina from the back of the eye.

The same kind of process causes age-related macular degeneration.

Hla and colleagues bred mice without S1P. "If you don't have the receptor, you don't get abnormal vessel growth in the retina," Hla said.

The mice without S1P grew normal vessels when they were stressed.

S1P interacts with five different vascular receptor proteins. Hla is concentrating on the number 2 receptor, which is found in high amounts in damaged vasculature, but rare in healthy tissue (S1P2).

This means that a designer drug could be developed to block the number 2 receptor in injured sites without affecting healthy blood vessels throughout the body, Hla said.

S1P also plays an interesting role in the ear. When humans are faced with danger, most blood vessels contract in response to adrenaline. However, vessels in the ears remain open, ensuring that the sense of hearing is not dulled. S1P2 apparently plays a role in this response, Hla said.

One question that remains is why the body produces S1P when it seems to be the culprit in vision loss. After all, there is no evolutionary advantage in loss of sight.

"Pathological lesions are usually repair processes gone awry," Hla said. "S1P2 may be needed for normal repairs."

UConn medical school graduate student Athansia Skoura worked with Hla on the research. The study appears in the September issue of the Journal of Clinical Investigation, and is available online at www.jcl.org.