Age-Related Macular Degeneration

UK leads on eye disease discoveries - CCR3

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Quelle: www.kentucky.com/211/story/835741.html

Posted on Fri, Jun. 19, 2009

UK leads on eye disease discoveries

By Jim Warren
jwarren@herald-leader.com

Discoveries by University of Kentucky researchers potentially could lead to a new way of simultaneously detecting and treating a type of macular degeneration, the leading cause of blindness in older adults.

The UK group, led by Dr. Jayakrishna Ambati, pinpointed a protein called "CCR3" that is a marker for "wet" type, age-related macular degeneration. They also used nanotechnology to develop a new way of detecting the marker in the eyes of test mice.

That technique some day might lead to a new test for early detection of macular degeneration before it starts to rob patients of their vision. And the detection technique potentially could block or slow the disease itself, UK says.

"The beauty of the detection is that it's a treatment in itself," said Ambati, who holds the Dr. E. Vernon and Eloise Smith Endowed Chair in Macular Degeneration at UK.

Researchers from the University of North Carolina, Cincinnati Children's Hospital, Boston Children's Hospital and other institutions collaborated with UK on the project.

The UK research - published online by the prestigious science journal Nature - applies only to wet-type macular degeneration, which produces the most severe vision loss. It would not help the more common "dry" type, which accounts for about 90 percent of cases.

Roughly 1.8 million mostly older Americans have advanced macular degeneration, which rarely occurs before age 50. The number of patients is expected to double over the next decade as the population ages.

In "dry" macular degeneration, yellow deposits form under the macula, the central part of the retina, weakening vision. In the wet type, abnormal blood vessels form and invade the retina, causing more rapid vision loss.

John Blaiklock, 78, of Lexington, has been battling macular degeneration in his right eye for about four years. He said faded vision makes reading difficult, particularly when it comes to hymnals in church, and has forced him to give up tennis.

"I used to play very regularly but not anymore," Blaiklock said. "I'm waiting for that miracle drug, I guess, to at least stop it from getting worse."

Ambati's team long has been searching for a chemical marker for macular degeneration. Three years ago, their focus shifted to a receptor protein called CCR3. When they examined samples of abnormal vessels from the eyes of macular degeneration patients, CCR3 kept turning up.

"We found that each and every one, without fail, had this protein," Ambati said Wednesday. "We now know that CCR3 is found on the surface of these abnormal blood vessels, and it's not on the surface of normal blood vessels."

According to Ambati, researchers think that when blood vessels become abnormal - the reason for that remains unclear - CCR3 speeds their growth.

"In this case, it causes the blood vessels to grow bigger, migrate and invade the retina," he said.

Next, the UK group found a way to detect CCR3 in the eyes of laboratory mice that had been given macro degeneration but hadn't yet started to lose vision.

Researchers placed tiny nanocrystals called "quantum dots" on CCR3 antibodies and injected them into the mice. The antibodies caused the quantum dots to stick to CCR3 molecules in the mice's eyes. Researchers then used a medical imaging technique that caused the quantum dots to fluoresce, or light up, becoming visible and revealing the presence of CCR3.

Ambati said researchers now hope to develop a similar testing technique that could detect the presence of CCR3 - and macular degeneration - in human eyes before vision loss occurs.

Equally important, Ambati said, the antibodies used in such a test also could block or slow the CCR3 protein's ability to promote abnormal vessel growth, in effect slowing the disease before it starts to cause damage.

"If you can block the CCR3, you can stop the vessels from growing," he said. "Once the vessels invade the retina, the horse has already left the barn. Drugs can slow the process, but irreparable damage has often already been done."

Ambati said the test wouldn't be offered to everyone. It probably would be reserved for individuals at high risk, he said, such as those who have macular degeneration in one eye and are likely to develop it in the other eye.

Researchers around the country say the findings are promising.

"This is an an exciting discovery for millions of people at risk," said Dr. Steven Ryan, a professor of ophthalmology at the University of Southern California. Ryan said in a prepared statement that UK's results are important because they offer the possibility of detection before vision is lost.

Harvard's Dr. Patricia D'Amore called the UK findings a "major breakthrough," that could lead to "the next generation of ... therapy for wet age-related macular degeneration."

According to Ambati, UK could start preliminary trials in a few human patients in about a year.


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