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Researchers find novel way to halt age-related vision decline


Boosting a protein linked to aging protects against age-related macular degeneration.

Researchers looking at the potential causes of age-related macular degeneration, a disease affecting about 20 million Americans, found that a specific protein could be the key to successfully treating this disease.
A study published June 5 in Science Translational Medicine found that by boosting the protein IRAK-M, protection is provided for the retina, and the disease could be prevented, or the progress of the disease could be arrested.

This newly discovered treatment option can significantly protect against this debilitating condition, Dr. Andrew Dick, ophthalmology professor at the University of Bristol, England, said in a press release. He said this discovery is the first research approach of macular degeneration to analyze genome studies, to identify genes associated with diseases.

Age-related macular degeneration (AMD) is a disease that affects the central vision but rarely causes blindness. It is the most common cause of severe vision loss for people 50 years old and older. AMD can start out with blurred vision, or the persistent sight of a black dot, and progress to the point that the central vision is no longer useful.

Risk factors for the disease include smoking and high blood pressure. AMD is believed to be caused by various environmental and lifestyle factors, but an exact cause has not been identified.

The macula is the central area of the retina, the nerve tissue at the back of the eye that transmits images through the optic nerve to the brain. There is no known cure for AMD, but there are treatments that have prevented the disease or its progress.

A Novel Way to Prevent Eye Disease

The researchers found that boosting levels of the protein in the retina protects against its degeneration. In their study, they said they identified IRAK-M as a key protein that fights off pathogens in the retinal pigment epithelium (RPE) the layer of cells beneath the retina that helps to keep the retina functioning properly.

They found that the presence of this protein decreased in the RPE as age increased in humans and mice, and is reduced further by the disease. Boosting of the protein protected RPE cells against inflammatory processes that occur in AMD, “suggesting a potential treatment for retinal degeneration,” the researchers said in their study.

“Our novel approach not only addresses the multiple pathways involved in treating AMD but also offers the most compelling and evidence-based strategy available today,” Dr. Ying Kai Chan, a member of the research team, said in the press release.

Because of the importance of this discovery and disease, Dr. Chan co-founded Cirrus Therapeutics, a pharmaceutical company, to develop related treatments for eye diseases. Dr. Dick, who also serves as director of the University of College London Institute of Ophthalmology, is Cirrus Therapeutics’ co-founder.

A Protein Connected With the Disease

In 2022, a research team at Sanford Burnham Prebys Medical Discovery Institute published a study on the discovery of the structure of a protein found in blood that is related to macular degeneration and other age-related diseases.

“Proteins in the blood are under constant and changing pressure because of the different ways blood flows throughout the body,” said Francesca Marassi, Prebys Medical professor and research team leader, in a press release. “For example, blood flows more slowly through small blood vessels in the eyes compared to larger arteries around the heart. Blood proteins need to be able to respond to these changes, and this study gives us fundamental truths about how they adapt to their environment, which is critical to targeting those proteins for future treatments.”

The researchers focused on vitronectin, which circulates at a high concentration in blood, among hundreds of proteins. They found that it is “a key player in many age-related diseases,” but especially in macular degeneration. Vitronectin is also found in cholesterol.

“This protein is an important target for macular degeneration because it accumulates in the back of the eye, causing vision loss. Similar deposits appear in the brain in Alzheimer’s disease and in the arteries in atherosclerosis,” Mr. Marassi said. “We want to understand why this happens and leverage this knowledge to develop new treatments.”

The researchers discovered the protein changes its shape and structure, as it flows through the bloodstream at different temperatures and varying pressures. These changes cause it to bond with calcium ions, which cause calcified plaque deposits to form. The researchers said these deposits are associated with macular degeneration and other diseases.

“It’s a very subtle rearrangement of the molecular structure, but it has a big impact on how the protein functions,” Mr. Marassi said. “The more we learn about the protein on a structural and mechanistic level, the better chance we have of successfully targeting it with treatments.”

Mr. Marassi expressed the hope that this discovery will lead to the development of treatments for macular degeneration because it will help the biotech industry to design antibodies that prevent the protein from binding with calcium.

“It will take some time to convert it into a clinical treatment, but we hope to have a working antibody as a potential treatment in a few years’ time,” Mr. Marassi said. “And since this protein is so abundant in the blood, there may be other exciting applications for this new knowledge that we don’t even know about yet.”



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