April 3, 2013
Cholesterol Lowering Eye Drops Could Treat Macular Degeneration
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redOrbit Staff & Wire Reports - Your Universe Online
The investigators, who detailed their findings online in the journal Cell Metabolism, discovered that age-related macular degeneration (AMD) and atherosclerosis — a condition in which the accumulation of fatty materials such as cholesterol and triglycerides causes artery walls to thicken — are both caused by the body´s inability to remove buildups of fat and cholesterol.
“Our increased understanding of cholesterol's role in the growth of ocular blood vessels helped us identify therapeutically modifiable pathways, opening up avenues for new treatments that may help us prevent blindness caused by macular degeneration,” senior study author Rajendra Apte, a professor of ophthalmology and visual sciences at the university, said Tuesday in a statement.
In AMD, the growth of new blood vessels leads to bleeding, scarring, and ultimately cell death, the researchers explained. The condition slowly destroys the part of the eye responsible for fine-detail vision.
Previous research had linked a type of cholesterol accumulation in white blood cells known as macrophages to the disorder. However, Apte and his colleagues are the first to examine the specific mechanisms by which those cells cause the growth of new blood vessels and potential blindness — as well as the first to examine the possible role of cholesterol metabolism in the entire process.
Apte´s team found that macrophages taken from both older mice and human macular degeneration patients contained low levels of ABCA1, a cholesterol transporter known to move cholesterol out of the cells. The presence of ABCA1 means that the old macrophages had accumulated large amounts of cholesterol, and were thus unable to inhibit the growth of new blood vessels.
In an attempt to restore cholesterol transport functions, the scientists focused on a pair of cholesterol regulators. One, Liver X Receptor (LXR), is known to promote cholesterol efflux. The other, microRNAs-33, has been shown to directly decrease ABCA1 expression.
The mice were then treated with either an eye drop or injection meant to activate LXR or a substance to a microRNA-33 inhibitor. Both substances increased ABCA1 protein levels and improved cholesterol transport in macrophages, resulting in a reduction in the growth of blood vessels, the researchers said.
“We were able to deliver“¦ an LXR agonist in eye drops,” first author Abdoulaye Sene, a post-doctoral fellow in Apte´s lab, explained in a separate statement. “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.”
“We have shown that we can reverse the disease cascade in mice by improving macrophage function, either with eye drops or with systemic treatments,” added Apte. “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.”