Findings have implications for macular degeneration and cancer tumor growth

A $1.9 million federal grant will support work at Cincinnati Children’s to explore how a cellular “policeman” controls the way blood vessels form new branches.

In 2011, research led by Richard Lang, PhD, director of the Visual Systems Group at Cincinnati Children’s, revealed a new molecular pathway used to suppress blood vessel branching in the developing retina. The findings, published in the journal Nature, could lead to new ways to treat retinal diseases and slow tumor growth in a variety of cancers.

The research focuses on the role myeloid cells – known as the “policemen of multicellular organisms” – play in determining how frequently blood vessels form new branches. By studying eye development in mice, Lang’s research team reports that myeloid cells use the Wnt-Flt1 pathway to regulate vascular branching.

Ramping up the expression of Flt1 slows down branching, which could be useful in fighting cancer tumors and eye diseases such as retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration. Conversely, turning down the process stimulates branching, which could help speed repair of other damaged tissues.

Until recent years, studying the function of myeloid cells has been a difficult task. This research was made possible by developing a mouse model that deletes targeted genes only in the myeloid cells, Lang says. If those genes were deleted elsewhere in the body, the developing mouse would not survive to reach birth.

The five-year grant from the National Eye Institute will allow Lang’s team to expand their findings.

“The retina is a great place to study angiogenesis,” Lang says. “This new grant provides funding to look for other molecular pathways that affect blood vessel patterning. Other researchers will be able to use this understanding to develop new agents to treat disease.”