by Dan Roberts
Originally published and updated, April 6, 2013
This is a continuously updated review of research since 2002 on cholesterol and age-related macular degeneration. It presents studies of statin treatment and it introduces recent findings regarding reduction of cholesterol by restoring macrophages.
Statins
Statins are a type of cholesterol-reducing drug that lower the levels of fats (lipids) in the blood, including cholesterol and triglycerides.
In 2002, researchers from the Centre for Eye Research in Melbourne, Australia completed a study that suggested important implications for people affected by macular degeneration. The research showed that taking cholesterol-lowering drugs could slow the progression of AMD, a conclusion drawn from observation of 580 subjects over a ten-year period. Dr. Robyn Guymer, head of the centre’s macular degeneration research unit, said that such drugs could lower the risk of developing AMD by as much as four times.
The reasoning was that, as people age, fatty deposits build up behind their retinae. In people with AMD, these deposits tend to be thicker, slowing down the circulation of the blood which supplies nutrients to the photoreceptors. Without proper nutrition, these cells wither, and vision deteriorates. Cholesterol-lowering drugs may help the body to clear the retinal vessels and slow down the progression of the disease. Dr. Guymer hoped to begin a two-year clinical trial to confirm the results of the initial study.
These conclusions were disputed in findings published in the February 1, 2003 issue of the British Medical Journal.
This study, conducted in the Netherlands, involved approximately 5,000 participants aged 55 years or more and at risk for maculopathy. Comparisons were made between those who developed maculopathy, who took any type of cholesterol-reducing drug, who took statins exclusively and who took no cholesterol-reducing drugs.
The study concluded that, “compared with patients who had never used cholesterol-reducing drugs, cumulative exposure for less than one month, for one month to a year, or for more than a year did not have a protective effect on the risk of maculopathy.” According to the researchers, the earlier studies had a “low statistical power,” since their results relied primarily on interview data. (Source: HealthCenterOnline.)
Another study, conducted in 2003 at the University of Alabama at Birmingham, found that 550 patients with maculopathy were 50% less likely to have taken a statin drug than were 5500 similar people who did not have maculopathy. There was no difference, however, between the groups in their use of other types of cholesterol-lowering drugs. (Source: British Journal of Ophthalmology, August 2003.)
One explanation for these differing results may be coming from research on inflammation.
The pharmaceutical products that are classed as statins (eg. Crestor, Zocor, and Lipitor) work by inhibiting an enzyme called “3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase.” This enzyme helps the liver to synthesize cholesterol. When inhibited by statins, cholesterol levels are lowered, and the heart benefits.
Statins, however, are also anti-inflammatories, and research holds inflammation highly suspect as a possible cause of macular degeneration. Some scientists are now thinking that high c-reactive protein levels (created by the liver) may cause inflammation in the retina, leading to cell damage. If inflammation can be reduced with statin drugs, it may turn out to be an effective preventative treatment for macular degeneration. On the other hand, aspirin, when compared to statins, has been shown to be equally effective for this purpose.
In April 30, 2008, a research team led by Catherine Cukras, M.D., Ph.D., medical retina fellow at the National Eye Institute, analyzed data from the Age-Related Eye Disease Study (AREDS), and followed 1,266 subjects for 11 years. The authors reported that statin use was statistically significantly associated with the development of advanced AMD. Of 481 patients who developed advanced AMD, 323 developed neovascular AMD, and 233 developed central geographic atrophy.
A more recent study, published in December 2009 (Maguire M, et al “Statin use and the incidence of advanced age-related macular degeneration in the complications of age-related macular degeneration prevention trial” Ophthalmol 2009; DOI: 10.1016/j.ophtha.2009.06.055), reported no significant link between statin use and progression of AMD to the advanced stage. This research examined data on 744 patients who were enrolled in the Complications of Age-Related Macular Degeneration Prevention Trial (CAPT).
Macrophages
Macrophages are key immune cells that remove cholesterol and fats from tissues. As they begin to malfunction from age, excessive cholesterol builds up. These lipid deposits gradually become more numerous in the retina, destroying the macula and leading to loss of central vision.
Researchers at Washington University School of Medicine in St. Louis speculate that drugs now being used to prevent artherosclerosis might be effective also in preventing wet macular degeneration. They reported in the April 2013 issue of Cell Metabolism that they have identified a protein (ABCA1) that macrophages use to clear fats and cholesterol. Through rodent studies, they discovered that an LXR agonist (T0-901317) could improve the level of ANCA1 in the aging macrophages. From this they think that the drug might also prevent new blood vessel growth and leakage in AMD patients, since inflammation is a direct result of cholesterol buildup. This, however, was not tested, and it cannot be tested in humans at this time, as LXR agonists are not yet approved for human use. This is promising research, but macrophage restoration as a treatment for wet AMD is still a few years away.
Source: Apte RS et al. Impaired cholesterol efflux in senescent macrophages promotes age-related macular degeneration. Cell Metabolism, vol. 17(4), published online April 2, 2013