AMD, four acronyms that hide 90% of all age-related vision loss. Age-related macular degeneration (AMD) is a degenerative disease that affects the macula, the central area of the retina, whose main symptom is blurred vision, altered perception of colors and the size of objects or sensation of dazzle before light stimuli, which makes life very difficult for those affected, most of whom are over 70 years of age.
There are two types of macular degeneration, the dry form, which accounts for 80% of cases and for which there are no effective treatments, and the wet form, for which there are therapies but whose results are generally temporary. For all these reasons, the search for a solution to this problem, which is estimated that by 2050 the global number of affected people will have doubled, seems to be a global need.
With this objective in mind, the study led by Francesca Marassi, professor at Sanford Burnham Prebys (USA) –one of the most complete non-profit drug discovery centers in the world– and published a few days ago in the Biophysical Journal, was born. is helping to unlock the molecular secrets of macular degeneration, and whose results describe the flexible structure of vitronectin, a key blood protein involved in macular degeneration and other age-related diseases, such as Alzheimer’s and atherosclerosis, so the finding could be relevant in the search for treatments for these health problems.
Look for changes in blood proteins to solve AMD
“Proteins in the blood are under constant and changing pressure due to the different ways blood flows throughout the body,” says Marassi. “For example, blood flows more slowly through the small blood vessels in the eyes compared to the larger arteries in the heart. Blood proteins must be able to respond to these changes, and this study gives us fundamental insights into how they adapt to their environment, which is critical to targeting those proteins for future treatments.”
Although there are hundreds of proteins in our blood, the research focused, as we said, on vitronectin, one of the most abundant. And it is that, apart from circulating in high concentrations in the blood, vitronectin is found in the scaffolding between cells and is also an important component of cholesterol.
“This protein is an important target for macular degeneration because it accumulates in the back of the eye and causes vision loss.”
“This protein is an important target for macular degeneration because it accumulates in the back of the eye and causes vision loss. Similar deposits appear in the brain in Alzheimer’s disease and in the arteries in atherosclerosis,” says Marassi. “We want to understand why this is happening and use this knowledge to develop new treatments.”
To address this question, the researchers were interested in learning how the protein changes its structure – the most important part in determining its function – at different temperatures and under different pressure levels, approximating what happens in the human body.
Detailed biochemical analysis revealed that the protein can subtly change its shape under pressure. These changes make it more readily bind calcium ions in the blood, which experts suggest leads to the buildup of calcified plaque deposits characteristic of macular degeneration and other age-related diseases.
“It is a very subtle rearrangement of the molecular structure, but it has a great impact on the functioning of the protein”, explains Marassi. “The more we learn about the protein at a structural and mechanistic level, the better chance we have of successfully targeting it with treatments.” Thus, it is expected that this structural knowledge will help speed up the development of treatments for macular degeneration because it will allow the design of personalized antibodies that selectively block the calcium binding of the protein without interrupting its other key functions for the organism.
“It will take some time to turn it into a clinical treatment, but we hope to have a working antibody as a potential treatment within a few years,” says Marassi. “And since this protein is so abundant in the blood, there may be other exciting applications for this new knowledge that we don’t yet know about.”
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