For years, researchers have been seeking a hard link between heart disease and age-related macular degeneration. But treatment—such as prescribing cholesterol-lowering statins to patients with AMD—has been disappointing.
Now, researchers at Washington University School of Medicine in St. Louis have found an important connection between AMD and atherosclerosis.1
Better yet, they tested an eye drop in older mice that not only halted but also reversed choroidal neovascularization.
“We were able to deliver the drug, called an LXR agonist, in eye drops,” says lead author Abdoulaye Sene, PhD. “And we found that we could reverse the macular degeneration in the eye of an old mouse. That’s exciting because if we could use eye drops to deliver drugs that fight macular degeneration, we could focus therapy only on the eyes and we likely could limit the side effects of drugs taken orally.”
Both AMD and atherosclerosis have the same underlying defect: the inability to remove a buildup of fat and cholesterol. Researchers have been investigating whether cholesterol-lowering eye drops, or other medications that might prevent the buildup of lipids in the retina, could prevent vision loss caused by AMD.
In this study, the investigators focused on macrophages, immune system cells that remove harmful materials such as cholesterol and fats from tissues. The scientists found that macrophages in both old mice and in patients with AMD have inadequate levels of the protein ABCA1, which transports cholesterol out of cells. As mice and humans age, they make less of this protein, and macrophages become less effective at engulfing and removing fat and cholesterol. As a result, the old macrophages accumulate high levels of cholesterol and cannot inhibit the CNV that occurs with wet AMD.
But when the researchers treated the macrophages with LXR agonist, it boosted levels of ABCA1, so the cells removed cholesterol more effectively. It also slowed the development of new blood vessels.
“We have shown that we can reverse the disease cascade in mice by improving macrophage function ... with eye drops or with systemic treatments,” says senior investigator Rajendra S. Apte, MD, PhD. “Some of the therapies already being used to treat atherosclerosis target this same pathway, so we may be able to modify drugs that already are available and use them to deliver treatment to the eye.”
Sene A, Khan AA, Cox D, et al. Impaired cholesterol efflux in senescent macrophages promotes age-related macular degeneration. Cell Metab; 2013 Apr 2;17(4):549-61.