Blocking an inflammatory receptor in the retinas of aging mice improves retinal health

A new research paper was published in Aging (Aging-US) on January 31, 2025, in Volume 17, Issue 2, titled "Cysteinyl leukotriene receptor 1 modulates retinal immune cells, vascularity and proteolytic activity in aged mice."

The study, led by first author and corresponding author Andreas Koller from the University Hospital of the Paracelsus Medical University, found that blocking an inflammatory receptor called CysLTR1 in the retinas of aging mice improved retinal health. These findings suggest a new approach to slowing age-related vision loss and protecting eye health in older adults.

Age-related vision problems are a growing concern worldwide, and inflammation plays a key role in damaging the retina over time. The retina is the part of the eye that captures light and sends visual signals to the brain, making it vital for clear eyesight. In this study, scientists focused on the CysLTR1 receptor, which is known to promote inflammation and is found in high amounts in the retina. They explored whether blocking this receptor could reduce the harmful effects of aging in the eye.

To achieve this, researchers treated aged mice with montelukast (MTK), a drug commonly used for asthma, which specifically blocks CysLTR1. The oral treatment lasted eight weeks and results were compared with both untreated aged mice and healthy young mice. After treatment, the older mice showed major improvements in retinal health.

One key finding was a reduction in immune cells called microglia, which tend to increase with age and contribute to chronic inflammation in the retina. With CysLTR1 blocked, the number of these immune cells dropped significantly, suggesting reduced retinal inflammation. Lower inflammation is linked to a lower risk of age-related eye diseases like macular degeneration.

"The reduction in immune cells caused by Cysltr1 suppression may dampen neuroinflammation, a known promoter of tissue aging."

Another important result was the restoration of blood vessel function. The tiny blood vessels in the retina had narrowed in aging mice, reducing blood flow and oxygen supply to the eye. MTK treatment increased the diameter of these vessels, improving circulation and possibly helping the retina work more efficiently.

The study also indicated that blocking CysLTR1 helped boost the retina's natural ability to clear out waste proteins. As we age, this cleaning process slows down, allowing harmful material to build up in the eye. After treatment, the aged mice had stronger proteasome activity-the system responsible for breaking down cellular waste-and fewer signs of waste accumulation.

Importantly, the treatment did not harm retinal nerve cells, which are essential for vision. This evidence indicates that the therapy was not only effective but also safe.

While more research is needed to confirm these results in humans, this study highlights the potential of repurposing MTK to protect against age-related vision decline. Because it is already an approved drug, testing it for age-related eye diseases like macular degeneration or diabetic retinopathy could move forward more quickly. Blocking inflammation and supporting the eye's natural cleaning systems may be a promising new way to preserve healthy vision in aging populations.