New Hope for Preventing Leading Cause of Blindness
Researchers have discovered a possible method to impede the advancement of age-related macular degeneration (AMD), a prevalent cause of vision loss in people over 50. This research may revolutionize treatments for this debilitating condition, potentially safeguarding eyesight for millions.
Potential Breakthrough in Treating AMD
A recent study conducted by the Washington University School of Medicine in St. Louis has pinpointed a potential method for slowing or even halting the progression of AMD. Scientists, along with their international partners, found that issues with cholesterol metabolism are linked to this form of visual impairment. This offers a fresh explanation for the connection between macular degeneration and cardiovascular disease, both of which are more prevalent with age.
The research, which involved human plasma samples and mouse models of macular degeneration, suggests that boosting the blood’s amount of apolipoprotein M (ApoM) resolves cholesterol processing issues. These issues contribute to cellular damage in the eyes and other organs. This could lead to novel treatments for AMD and possibly some forms of heart failure triggered by similar cholesterol processing problems.
“Our study points to a possible way to address a major unmet clinical need. Current therapies that reduce the chance of further vision loss are limited to only the most advanced stages of macular degeneration and do not reverse the disease. Our findings suggest that developing treatments that increase ApoM levels could treat or even prevent the disease and therefore preserve people’s vision as they age.”
—Rajendra S. Apte, MD, PhD, Senior Author
The study, published in the journal Nature Communications on June 24, further revealed that in people with AMD, doctors can detect cholesterol-rich deposits beneath the retina. In early stages, vision might remain intact, though these deposits exacerbate inflammation. This ultimately leads to a gradual loss of central vision.
According to the CDC, AMD affects around 1.8 million Americans over the age of 40, with numbers expected to rise as the population ages (CDC 2023).
Understanding the Connection
In recent years, evidence has linked ApoM to protective roles in maintaining healthy cholesterol metabolism. Researchers, including Ali Javaheri, MD, PhD, were curious whether declining ApoM levels, common with age, contribute to the dysfunctional cholesterol metabolism implicated in aging-related diseases, like macular degeneration and heart disease.
The study showed that patients with macular degeneration have reduced ApoM levels compared to healthy individuals. Previous work by Dr. Javaheri indicated that patients with heart failure also exhibit lower ApoM levels in the blood.
This research determined that ApoM is vital in “good cholesterol” pathways. These pathways eliminate excess cholesterol from the body via the liver. The findings propose that with low ApoM, cells in the retina and heart have difficulties metabolizing cholesterol deposits. This results in inflammation and cellular damage.
Researchers increased ApoM levels in mouse models of macular degeneration to reverse these harmful effects. This led to improved retinal health, improved function of light-sensing cells, and reduced cholesterol deposits. The researchers also discovered that ApoM needs to bind to sphingosine-1-phosphate (S1P) for its beneficial effects.
Future Implications
Drs. Apte and Javaheri are collaborating with Mobius Scientific, a WashU startup, to translate this understanding of ApoM’s role into novel treatments for AMD. The implications of these findings could also extend to interventions for heart failure patients.
Dr. Javaheri stated, “One of the exciting things about this collaboration is realizing the links between retinal pigment epithelial cells and heart muscle cell, which are both vulnerable to low ApoM. It is possible that the interaction between ApoM and S1P is regulating cholesterol metabolism in both cell types. We look forward to exploring strategies to increase ApoM in ways that could help the eye and the heart maintain healthy cholesterol metabolism over time and stave off two major diseases of aging.
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