Early detection and prevention of macular degeneration takes step forward

Neovascular or "wet-type" macular degeneration is the leading cause of blindness in older adults, with 10 to 12 million Americans affected. With this condition, the eye experiences an invasive growth of new blood vessels in the thin vascular layer that offers nourishment and oxygen to the eye --  a condition called choroidal neovascularization (CNV). When those abnormal blood vessels invade the retina, the individual loses site in the central part of the eye. And unfortunately, once the damage has occurred, it cannot be undone. "Once the vessels invade the retina, the horse has already left the barn," says Dr. Jayakrishna Ambati at the University of Kentucky. "At that point, drugs can slow the process, but irreparable damage has often already been done. This is why finding a means for early detection and intervention is so important."

Dr. Ambati believes he and his team of researchers are one step closer to advancing the early detection and prevention of the disease. The researchers have discovered a biological marker, a receptor known as CCR3, which is expressed on the surface of CNV vessels in humans, but not in normal vascular tissue. "CCR3 chemokine receptor is known to be a key player in the allergic inflammation process, but Dr. Ambati's studies have now identified CCR3 as a key marker of the CNV process involved in AMD. If researchers can determine why CCR3 is expressed in the CNV of AMD patients, they could further understand AMD disease progression," says Dr. Grace L. Shen, director of the ocular immunology and inflammation program at the National Eye Institute. And notes Dr. Ambati: "This is a major paradigm shift in macular degeneration research. With CCR3, we have for the first time found a unique molecular signature for the disease. This brings us closer than we have ever been to developing a clinical diagnostic tool to discover and treat the disease early, before vision is lost."

So how exactly did Dr. Ambati and his team discover the CCR3 marker? The team attached anti-CCR3 antibodies to "quantum dots" -- tiny semiconductor nanocrystals -- and injected the dots into the living eyes of mice. The quantum dots attach to CCR3 on the surface of the abnormal blood vessels, allowing them to be seen with conventional ocular angiography techniques -- even before the blood vessels have penetrated the retina. "This is an exciting discovery for the millions of people at risk of developing wet macular degeneration, because this new imaging technology introduces the possibility of detecting pathological neovascularization before retinal damage and vision loss occur," says Dr. Stephen J. Ryan, professor of ophthalmology at the University of Southern California and member of the National Academy of Sciences' Institute of Medicine.

The researchers also discovered that not only does CCR3 provide a "unique signature for CNV, but the gene actively promotes the growth of these abnormal blood vessels in the eye." Therefore, the same antibodies could potentially be used to both detect CNV and prevent macular degeneration. And in fact, the researchers treated the mice with the anti-CCR3 antibodies, reducing CNV by about 70 percent, slightly more than VEGF-based treatments now in clinical trial.

News Release: Major breakthrough in macular degeneration  www.newswise.com June 14, 2009