June 20, 2024

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Age-related macular degeneration: Study finds surprising culprit

A new study suggests that a molecule that usually suppresses harmful blood vessel growth may do the opposite in a type of sight loss called age-related macular degeneration (AMD). If confirmed in future studies, the discovery could lead to more effective treatments.

More than 1.8 million Americans aged 40 years and over have AMD, according to the Centers for Disease Control and Prevention (CDC).

According to one source, 10-15% of people with AMD have a more severe form of the disease known as “wet” AMD that progresses more rapidly.

Wet AMD involves inflammation and excessive growth of fragile blood vessels beneath the macular. This is the central part of the retina that allows the eye to see fine detail. These vessels leak blood and fluid, which damages photoreceptors in the macular and results in loss of central vision.

Research into other conditions involving nerve damage, such as Alzheimer’s and Parkinson’s disease, suggests that an immune-signaling molecule called interleukin-4 (IL-4) may play an anti-inflammatory, protective role.

IL-4 is also known to suppress blood vessel growth, which may help prevent the growth of tumors.

In addition, bone marrow cells usually help the body repair damaged tissues, including blood vessels.

Researchers in the Division of Ophthalmology and Visual Science at Tottori University in Japan set out to discover whether IL-4 and bone marrow cells protect the photoreceptors of people with wet AMD.

The team published their finding in the journal eLife.

First, they measured levels of IL-4 in the aqueous humor — the watery fluid inside the eyes — of 234 people with wet AMD at their first treatment session. They also collected samples of aqueous humor from 104 older people undergoing surgery for cataracts, who served as controls.

People with wet AMD had higher levels of IL-4 than those in the control group.

The researchers also found that mice with a condition that mimics AMD had raised levels of IL-4 in their eyes. To determine whether the molecule is protective or harmful, they injected IL-4 into the bloodstream of the mice and found it increased excessive blood vessel growth in their eyes.

Injecting the mice with an antibody that blocks IL-4 production had the opposite effect, reducing blood vessel growth.

The researchers went on to use cell culture experiments to show that IL-4 helps to control the response of mice bone marrow cells and the growth of new retinal blood vessels. In its absence, the fragile blood vessels that characterize AMD were unable to grow.

“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,” says Takashi Baba, co-first author of the study.

The researchers conclude that far from protecting photoreceptors by inhibiting the growth of new blood vessels — which is what they expected — IL-4 promotes the growth of more blood vessels.

“These results were surprising and suggest that normally helpful immune responses can instead cause more harm,” says co-first author Dai Miyazaki.

In their paper, the authors write that while IL-4 is known to reduce inflammation, prevent the growth of new blood vessels, and protect nerve cells, these functions appear to be dependent on the context.

Nonetheless, they believe that their surprise finding offers new possibilities for treating AMD.

“As IL-4 plays a key disease-promoting role in AMD, it may serve as a target for new treatments to treat this condition,” says Miyazaki.

These treatments could block either IL-4 itself or the receptors to which it binds.

For now, however, the findings remain preliminary and will need to be investigated further to confirm the researchers’ conclusions.

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