Could a Heart Disease Protein Hold the Key to Preventing Vision Loss from AMD?

A protein that can lower high cholesterol could slow the progression of age-related macular degeneration (AMD), according to a study in mice and human tissue by researchers at the Washington University School of Medicine in St. Louis.

Rajendra S. Apte, M.D., Ph.D.

“Our study points to a possible way to address a major unmet clinical need,” senior author Rajendra S. Apte, M.D., Ph.D., the Paul A. Cibis Distinguished Professor of Ophthalmology and Visual Sciences at WashU Medicine, said in a news release. “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.”

Age-related macular degeneration (AMD) is a leading cause of blindness in people over the age of 50. It's an eye disease that causes damage to the macula, the part of the retina that controls sharp, straight-ahead vision. It is associated with the build-up of lipoprotein deposits. In 2019, an estimated 19.8 million (12.6%) Americans aged 40 and older were living with age-related macular degeneration, according to the CDC.

In macular degeneration, cholesterol deposits under the retina can be seen during an eye exam, according to Apte. In early stages, vision might still be normal, but the deposits increase inflammation and cellular damage, which eventually leads to gradual loss of vision.

The research of Apte and his colleagues suggests that increasing the amount of the protein apolipoprotein M (ApoM) can address the processing of cholesterol that leads to cellular damage. The study, published recently in Nature Communications, suggests that when ApoM is low, cells in the retina and heart muscle can’t correctly metabolize cholesterol deposits.

Ali Javaheri, M.D., Ph.D.

Research previously done by co-senior author Ali Javaheri, M.D., Ph.D., an assistant professor of medicine, showed that patients with various forms of heart failure also had reduced levels of ApoM in the blood. This study suggests that ApoM is a key component in the “good cholesterol” pathways.

To see if they could reverse the harmful effects of low ApoM, the researchers increased ApoM levels in mice with macular degeneration. The mice showed evidence of improved retinal health, improved function of light-sensing cells in the retina and reduced accumulation of cholesterol deposits. In the mice, researchers also found that ApoM needs to bind to a molecule called sphingosine-1-phosphate (S1P) to get the benefits of ApoM.

Researchers also looked at plasma samples of 53 people with AMD, and they found reduced levels of ApoM compared with healthy controls.

This research was supported by a grant from the National Institutes of Health.

Mobius Scientific, a Washington University startup company, is working to harness this knowledge of ApoM to develop new approaches to treating or preventing macular degeneration. The company’s platform aims to treat lipid accumulation, the root cause of many common diseases. The company was founded in August 2023 by Nehal Mehta, M.D.,

“One of the exciting things about this collaboration is realizing the links between retinal pigment epithelial cells and heart muscle cells, which are both vulnerable to low ApoM,” Javeheri said in the news release.