In the new study, Apte and his team found that macrophages taken from both old mice and human AMD patients had low levels of ABCA1, a cholesterol transporter known to move cholesterol out of the cells. As a result, these old macrophages accumulated high levels of cholesterol and were unable to inhibit the growth of new blood vessels. In order to restore cholesterol transport, the researchers focused on two key cholesterol regulators: Liver X Receptor (LXR), whose activation is known to promote cholesterol efflux, and microRNAs-33, which has been shown to directly decrease ABCA1 expression. Old mice were treated with either an LXR agonist, delivered via eye drops or injection, or a microRNA-33 inhibitor. Both of these drugs increased ABCA1 protein levels and improved cholesterol transport in macrophages, resulting in a reduction in the growth of blood vessels. Because the LXR agonist can be delivered with eye drops, it could potentially cause fewer side effects.
"Abnormal blood vessel growth is a characteristic of not only AMD, but also diverse disease processes outside the eye, including cancers and atherosclerosis, which are both associated with significant morbidity and mortality," Apte says. "Our findings may have significant relevance in our understanding of the pathobiology of these conditions."