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Study Finds Potential Cause of Age-Related Macular Degeneration
Date:3/17/2008

Data could lead to new drugs to check vascular proliferation that is hallmark of eye disease

MONDAY, March 17 (HealthDay News) -- Researchers have pinpointed a biological pathway that may block the blood vessel proliferation and leakiness behind most cases of blindness in the United States.

Though still preliminary, the University of Utah study suggests a new therapeutic target for such ophthalmic diseases as age-related macular degeneration (AMD) and diabetic retinopathy, as well as other conditions marked by inflammation and vascular leakiness, including cancer and certain traumatic injuries.

"I think it is very strong science," said Dr. George A. Williams, chairman of the department of ophthalmology at William Beaumont Hospital in Royal Oak, Mich. "It identifies a promising preliminary observation that is going to require a lot more development."

That observation involves a cell surface protein called Roundabout (Robo)-4. Other Robo family members play a role in neuronal growth and guidance, but Robo4 is different, said senior study author Dr. Dean Li, of the University of Utah, "mostly in that it was not expressed in nerves but in blood vessels."

Li has spent five years trying to understand the biology of Robo4. "We have been trying to figure out, why is this protein on blood vessels, and that is what this article answers -- what does this thing do?" he explained.

Li, along with Dr. Kang Zhang, also of the University of Utah, mutated the Robo4 gene in mice. They then characterized the behavior of cells from these mutant mice in response to the growth factor VEGF in the presence and absence of Robo4's binding partner, a protein called Slit2.

Normally, VEGF promotes angiogenesis, inducing vascular cell division, migration and vessel formation via its receptor. VEGF activity is responsible for normal vascular growth, but it also has a dark side, inducing the damage in AMD, diabetic
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