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St. louis, MO – A groundbreaking study from Washington University School of Medicine indicates that boosting levels of a molecule called apolipoprotein M (ApoM) could potentially prevent or slow the progression of age-related macular degeneration (AMD), a primary cause of blindness in individuals over 50. The research, published in Nature Communications on June 24, 2025, highlights the role of cholesterol metabolism in this vision-impairing condition and its connection to cardiovascular disease.
The Role of apom in Preventing Macular Degeneration
The study, utilizing human plasma samples and mouse models, revealed that increasing ApoM in the blood corrects cholesterol processing issues that lead to cellular damage in the eyes and other organs. This finding suggests that therapies aimed at increasing ApoM could be a novel strategy for treating or preventing AMD and potentially some forms of heart failure.
Did You know? Age-related macular degeneration affects an estimated 8 million Americans in its early stages [[3]].
Dr. Rajendra S. Apte, the Paul A. Cibis Distinguished Professor of Ophthalmology and Visual Sciences at WashU Medicine and senior author of the study, emphasized the importance of these findings. “Our study points to a possible way to address a major unmet clinical need,” he stated. “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.”
Cholesterol’s Impact on Macular Degeneration
In macular degeneration, cholesterol-rich deposits are visible under the retina during an eye exam.While vision may initially be normal, these deposits trigger inflammation and other damaging processes, leading to gradual central vision loss. the “dry” form of AMD can cause damage to cells in the central retina, resulting in geographic atrophy, a type of neurodegeneration similar to that seen in Alzheimer’s disease. Dry AMD can also progress to “wet” AMD, characterized by abnormal blood vessel growth that further damages vision.
Geographic atrophy and wet macular degeneration represent advanced stages of the disease accompanied by important vision loss. although some treatments exist for advanced AMD, they cannot reverse the underlying disease process.
ApoM: A Common Link Between Eye Disease and Heart Failure
Recent evidence indicates that ApoM acts as a protective molecule with anti-inflammatory properties and plays a crucial role in maintaining healthy cholesterol metabolism. Dr. Apte and Dr.Ali Javaheri, a cardiologist and assistant professor of medicine, investigated whether reduced ApoM levels, which naturally decline with age, could contribute to the dysfunctional cholesterol metabolism underlying AMD and heart disease.
Their research demonstrated that patients with macular degeneration have lower levels of ApoM in their blood compared to healthy individuals. Previous work by Dr.Javaheri also revealed reduced ApoM levels in patients with various forms of heart failure.
Pro Tip: Maintaining healthy cholesterol levels through diet and exercise may help support overall eye health.
The study further revealed that ApoM is a vital component of the “good cholesterol” pathways responsible for removing excess cholesterol from the body through the liver. When ApoM levels are low, cells in the retina and heart muscle struggle to metabolize cholesterol deposits, leading to inflammation and cellular damage.
Reversing the Effects of Low ApoM
To assess the impact of increasing ApoM levels, researchers used genetic modification and plasma transfer in mouse models of macular degeneration. The results showed improved retinal health, enhanced function of light-sensing cells, and reduced accumulation of cholesterol deposits. They also discovered that ApoM triggers a signaling pathway that breaks down cholesterol in cellular compartments called lysosomes.
the researchers also found that ApoM must bind to sphingosine-1-phosphate (S1P) to achieve its beneficial effects in the mice.
Future Treatments and Implications
Drs. Apte and Javaheri are collaborating with Mobius Scientific, a WashU startup, to develop new approaches for treating or preventing macular degeneration by leveraging their knowledge of ApoM’s role. The findings also hold promise for future interventions aimed at raising ApoM levels in patients with heart failure.
“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,” Javeheri said. “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.”