Study Finds Potential Cause of Age-Related Macular Degeneration

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The study was published in the March 16 online edition of Nature Medicine.

"What we are saying is the cells of the blood vessels have a protein receptor, and this is called Robo4, and if you activate the Robo4 receptor, by giving it a protein that binds to it, the blood vessel cells know the cells shouldn't leak and grow," Li said.

According to Li, that idea makes sense biologically.

"In everything in biology, there is a yin and a yang," he said. Just as there are factors that induce vascular growth and destabilization, there must also be factors to dampen that effect, "because every time you get sick and have interleukins in the body, you don't want the vasculature to destabilize. You want a balance between stabilization and destabilization."

Several drugs targeting the VEGF-signaling pathway have already been approved by the U.S. Food and Drug Administration, including Avastin, Lucentis and Macugen. Li said the Robo4/Slit2 biological pathway presents an alternative therapeutic target.

"You can block the destabilizing/regenerative factors [like VEGF]," he said, "but another way of doing it is to activate a signal to block destabilization. And I think this is the first proof of principle that this is a viable therapeutic option."

The study "identifies a new pathway by which we may be able to further inhibit VEGF-mediated effects," agreed Williams. "And if that is in fact true -- and the data look very compelling in this publication -- then there is potential that this could represent a new mechanism by which we could inhibit the role of VEGF in neovascular AMD."

Indeed, the authors tested that theory directly, by injecting Slit2 protein into the eyes of mouse models of AMD and diabetic retinopathy. In both cases, Slit2 reduced the angiogenesis that is a hallmark of disease.

But Williams noted that this same approach would not likely be viable therapeutically. Instead, a Slit2 molecular agonist (that is, a molecular mimic) would need to be developed and tested in humans -- a process that could take a decade or more before arriving in the clinic, he said.

AMD is the leading cause of blindness in Americans over the age of 55, according to the American Macular Degeneration Association, affecting more than 10 million individuals.

More information

For more on diseases of the eye, visit the U.S. National Eye Institute.