Targeting Cholesterol Buildup in the Eye May Help Slow Age-Related Macular Degeneration

Photograph of a retina with wet age-related macular degeneration

A new study, published on April 2, 2013 as a “freely available featured article” in the journal Cell Metabolism, indicates that lowering the levels of cholesterol in the eye could possibly prevent the growth of blood vessels that cause age-related macular degeneration (AMD). The study was conducted with animal models (i.e., mice) and immune cells taken from human subjects with AMD. The researchers hope to conduct clinical trials with human subjects within the next five years.

About the Research

The study is entitled Impaired Cholesterol Efflux in Senescent Macrophages Promotes Age-Related Macular Degeneration. (Translation: A reduction in cholesterol outflow in older, less efficient macrophages, which are a type of immune cell, can possibly promote the development of age-related macular degeneration.)

The study was authored by Abdoulaye Sene, Aslam A. Khan, Douglas Cox, Rei E.I. Nakamura, Andrea Santeford, Bryan M. Kim, Rohini Sidhu, Michael D. Onken, J. William Harbour, Shira Hagbi-Levi, Itay Chowers, Peter A. Edwards, Angel Baldan, John S. Parks, Daniel S. Ory, and Rajendra S. Apte, who represent the following institutions: Washington University School of Medicine, Saint Louis, MO; Hadassah-Hebrew University Medical Center, Jerusalem, Israel; David Geffen School of Medicine, University of California, Los Angeles; Saint Louis University, Saint Louis, MO; and Wake Forest School of Medicine, Winston-Salem, NC.

The mission of the journal Cell Metabolism is to provide a forum for the exchange of ideas and concepts across the entire biologic/metabolic research community, cultivating new research areas and emphasizing cross-disciplinary collaborations in basic research and clinical investigation.

About Macular Degeneration

Age-related macular degeneration (AMD) is a progressive eye condition, affecting as many as 15 million Americans and millions more around the world. The disease attacks the macula, which is the part of the retina that provides our sharpest and clearest central vision. AMD can reduce contrast sensitivity and color perception and diminish the clear, “straight ahead” central vision that is necessary for reading, driving, identifying faces, watching television, doing fine detailed work, safely navigating stairs, and performing other daily tasks we take for granted.

There are two types of age-related macular degeneration: dry (atrophic) and wet (neovascular). It’s possible to experience the wet type in one eye and the dry type in the other; in addition, the dry type can progress to wet in approximately 10-15% of cases.

The dry type affects approximately 85-90% of individuals with AMD. Its cause is unknown, it tends to progress more slowly than the wet type, and there is not yet an approved treatment or cure. In dry AMD, small white or yellowish deposits, called drusen, form on the retina, beneath the macula, causing it to deteriorate or degenerate over time.

The wet type affects approximately 10-15% of individuals. In wet AMD, the choroid (a part of the eye containing blood vessels that nourish the retina) begins to sprout abnormal blood vessels that develop into a cluster under the macula. These new blood vessels tend to break, bleed, and leak fluid, causing the macula to lift up and pull away from its base. This results in a rapid and severe loss of central vision.

More about the Study

From a National Institutes of Health (NIH) news release:

Cholesterol build-up in arteries and veins, or atherosclerosis, occurs as a natural consequence of aging. Likewise, in AMD, cholesterol is known to accumulate in the eye, within deposits called drusen.

The study … shows that large cells called macrophages appear to play a key role in clearing cholesterol from the eye, and that with aging, these cells become less efficient at this task.

Eye drops containing a type of drug known to promote cholesterol release from macrophages, called a liver X receptor (LXR) agonist [i.e., a drug that stimulates cell activity], helped restore macrophage function and prevent AMD progression in a mouse model.

What triggers neovascular AMD is unclear. Drusen, and the cholesterol within them, have been prime suspects. And based on genetic studies, including a recent AMD genetic analysis, the immune system appears to play a role, too. But researchers have had few details to connect these two pathways.

Study leader Rajendra Apte, M.D., theorizes that macrophages, a type of immune cell, may provide a crucial link. Macrophages, literally “big eaters” in Greek, act like garbage collectors. They scavenge for debris, engulf it, and process it.

In previous studies, Dr. Apte found that macrophages normally help limit the growth of new blood vessels in the eye, but with age, the cells lose this ability. The new study suggests that prior to these changes, old macrophages become less efficient at processing cholesterol.

“Ideally, macrophages should take up cholesterol, process it, and spit it out into the bloodstream. In AMD, we think the cells are ingesting cholesterol but not able to spit it out, so you get these inflamed macrophages that promote blood vessel growth…. If we could prevent the blood vessels from growing, it would be better than trying to eliminate them after the fact,” Dr. Apte said. “LXR agonists or other drugs to help macrophages clear away cholesterol might help.”

Additional Information

VisionAware will continue to provide updates for ongoing macular degeneration research as they become available. You can read more information about genetic risk factors for AMD at A Nationwide Study Is Investigating Genetic and Other Risk Factors for Macular Degeneration on the VisionAware blog.

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In April, during National Minority Health Awareness Month, visit to learn more about normal vision changes as we grow older, the difference between a vision screening and an eye examination, the different types of eye care professionals, and questions to ask during an eye examination.