Study finds unexpected suspect in age-related macular degeneration

May 05, 2020

Scientists have identified an unexpected player in the immune reaction gone awry that causes vision loss in patients with age-related macular degeneration (AMD), according to a new study published today in eLife.

The findings suggest that an immune-stimulating protein called interleukin-4 (IL-4) and its receptor may be promising targets for new drugs to treat AMD, a common form of age-related vision loss.

In patients with AMD, inflammation in the eye triggers excessive growth of new blood vessels in the center of the retina. This process damages the photoreceptors in the eye and leads to progressive vision loss. Normally, bone marrow cells help the body repair damaged tissues, while IL-4 helps suppress excessive blood vessel growth. Co-first author Takashi Baba, Junior Associate Professor in the Division of Ophthalmology and Visual Science at Tottori University, Japan, and his colleagues decided to look at whether these players might be helpful in patients with AMD. "The purpose of our study was to determine whether bone marrow cells and IL-4 protect the photoreceptors from neurodegeneration in patients with AMD," Baba explains.

To do this, the team measured levels of IL-4 in the eyes of 234 patients with AMD and 104 older individuals undergoing surgery for cataracts. They found that those with AMD had higher levels of IL-4 than those undergoing surgery.

Next, they found that IL-4 was also elevated in mice with a condition that mimics AMD. To determine if IL-4 was helping or harming the animals, they administered them with IL-4 and found that it increased the excessive growth of blood vessels in the eye. An antibody that blocks IL-4 production reduced this blood-vessel growth. Mice with the AMD-like condition that were genetically engineered to lack IL-4 also had less blood-vessel growth.

"Our results show that IL-4 plays a crucial role in excessive blood-vessel growth by recruiting bone marrow cells that aid this growth to the lesion in the eye," Baba says.

"These results were surprising and suggest that normally helpful immune responses can instead cause more harm," adds co-first author Dai Miyazaki, Associate Professor at the Division of Ophthalmology and Visual Science, Tottori University. "As IL-4 plays a key disease-promoting role in AMD, it may serve as a target for new treatments to treat this condition."
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Reference

The paper 'Role of IL-4 in bone marrow driven dysregulated angiogenesis and age-related macular degeneration' can be freely accessed online at https://doi.org/10.7554/eLife.54257. Contents, including text, figures and data, are free to reuse under a CC BY 4.0 license.

For more research from authors based in Japan, explore our latest collection at elifesci.org/highlights-from-japan.

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Emily Packer, Senior Press Officer
eLife
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About eLife

eLife is a non-profit organisation created by funders and led by researchers. Our mission is to accelerate discovery by operating a platform for research communication that encourages and recognises the most responsible behaviours. We work across three major areas: publishing, technology and research culture. We aim to publish work of the highest standards and importance in all areas of biology and medicine, while exploring creative new ways to improve how research is assessed and published. We also invest in open-source technology innovation to modernise the infrastructure for science publishing and improve online tools for sharing, using and interacting with new results. eLife receives financial support and strategic guidance from the Howard Hughes Medical Institute, the Knut and Alice Wallenberg Foundation, the Max Planck Society and Wellcome. Learn more at https://elifesciences.org/about.

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