In the 2 April issue of Cell Metabolism, senior investigator Rajendra S. Apte, of the Washington University School of Medicine in St. Louis in the US, and colleagues, report how AMD and atherosclerosis share a common underlying problem: an inability to remove remove a buildup of fat and cholesterol.
For their study, Apte, a Paul A. Cibis Distinguished Professor of Ophthalmology and Visual Sciences, and colleagues worked with mice and human cells and showed how deposits of cholesterol contribute to macular degeneration and atherosclerosis.
They suggest the same process may also be behind the growth of blood vessels in some types of cancer.
Patients with atherosclerosis are often prescribed cholesterol-lowering drugs to keep their arteries clear. The researchers suggest some of these drugs may have potential to treat patients with macular degeneration.
Age-Related Macular Degeneration (AMD)Age-related macular degeneration (AMD) is a painless eye condition that leads to gradual loss of central vision. It is the leading cause of vision loss in Americans over 50.
As AMD develops in a person their central vision becomes increasingly blurred so they gradually struggle to read print, recognize people's faces, or drive a car.
As it only affects the macula, the part of the retina responsible for central vision, the affected person retains peripheral vision, so it will not cause complete blindness.
When doctors examine the eye of a person with AMD they can see fatty deposits beneath the retina. As these grow and proliferate, they slowly destroy the central part of the retina.
There are two types of AMD: dry and wet. Dry is the most common and least serious form and accounts for 9 out 10 cases and vision loss develops slowly over many years.
Wet AMD is more serious and without treatment it can worsen very quickly. It develops when abnormal blood vessels grow under the macula and damage its cells. Around 1 in 10 people with dry AMD go on to develop wet AMD.
AtherosclerosisAtherosclerosis is where arteries become clogged by fatty molecules such as cholesterol. The fatty substances stick to the artery walls and form plaques or atheromas. It is a major risk factor for cardiovascular disease.
The condition is potentially serious because as the plaque builds up, the arteries harden and narrow, restricting blood flow and supply of essential nutrients and oxygen to organs. Also, if a plaque bursts, it can cause a blood clot, blocking the blood supply to the heart (triggering heart attack) or brain (which can cause stroke).
While it is not very clear exactly how arteries become clogged, we know that having high cholesterol is a risk factor, as is having high blood pressure, smoking, being overweight or obese, having diabetes, eating a high-fat diet, and lack of exercise.
To reduce the risk from high cholesterol, patients can be prescribed certain cholesterol-lowering medications, such as statins.
Protein In Macrophages Identified As Key to Cholesterol RemovalFor their study, Apte and colleagues focused on macrophages, important immune cells that remove fats like cholesterol.
They identified a protein called ABCA1 that macrophages need to be able to clear away fats and cholesterol out of cells.
They found that macrophages from old mice and patients with AMD, don't have enough of the protein. The result is that these old macrophages then become bloated with cholesterol, leading to an inflammatory process that promotes new blood vessels that compound the damage to the macula. These new blood vessels are a key feature of wet AMD.
Apte explains in a statement how:
"Ultimately, that inflammation creates a toxic mix of things that leads to new blood vessel growth," adding that:
"Most of the vision loss from 'wet' macular degeneration is the result of bleeding and scar-tissue formation related to abnormal vessel growth."
Cholesterol-Lowering Drugs May have Potential for Treating AMDWhen the researchers treated the macrophages of old mice with a drug that restored the protein, the cells were able to remove cholesterol effectively and the growth of new blood vessels slowed down.
Similar results were obtained by repeating this experiment with human cells:
"Monocytes from older humans with age-related macular degeneration showed similar changes," write the researchers.
They were able to deliver the drug, called an LXR agonist, in eye drops, and found they could reverse the macular degeneration in the old mice.
Apte says in a statement:
"Based on our findings, we need to investigate whether vision loss caused by macular degeneration could be prevented with cholesterol-lowering eye drops or other medications that might prevent the buildup of lipids beneath the retina."
Using eye drops to fight macular degeneration would be a great benefit because therapy would then focus only on the eyes and would limit any potential side effects from oral medication.
The researchers suggest that the same pathway may also provide a target for tackling other diseases where macrophages are important, such as atherosclerosis and certain types of cancerous tumors that rely on the formation of new blood vessels.
The hope is that since some available drugs already target this pathway to treat atherosclerosis, perhaps a treatment for AMD lies in simply evaluating modifications of them for use in the eye.
In 2012, researchers from Ireland reported how controlling or raising levels of the immune system component IL-18 could prevent dry AMD progressing into the wet form of the disease.
Written by Catharine Paddock PhD