Age-related macular degeneration is one of the main causes of vision loss after 50 in industrialized countries. Scientists from the University of Fribourg have shown in two recent studies that this process can be countered thanks to a natural “recycling” mechanism in cells.

As populations age, retinal diseases like Age-Related Macular Degeneration (AMD) are affecting a growing number of people worldwide. These disorders involve cells that are essential to a healthy eye and how it operates. Both, photoreceptors, which capture light, are affected as well as cells of the retinal pigment epithelium, a single cell layer that nourishes and supports the photoreceptors. Over time these cells accumulate waste products, including damaged proteins. Normally they have effective systems to eliminate these malfunctioning elements. With age, however, these mechanisms gradually weaken. Waste accumulates in the cells, causing significant stress and eventually leading to vision loss . Understanding why cellular cleaning systems stop working would boost hopes of one day slowing or even stopping the progression of these conditions.

Recycling proteins
A University of Fribourg team headed by Professor Patricia Boya, working with American and Spanish partners, focused on a natural “cleaning” mechanism in cells called chaperone-mediated autophagy (CMA). Simply put, cells possess an internal recycling system thanks to which specialized proteins called chaperones locate damaged proteins and ferry them to specialized structures, lysosomes, where they are degraded.

This system acts like a true selective sorting service inside the cell. The scientists demonstrated that the system is especially active in retina cells, where it provides indispensable quality control. When this mechanism malfunctions, as is the case in patients with these eye disorders, defective proteins pile up and the cells are increasingly stressed. They quickly lose their ability to function properly.

Repairs may be possible
The researchers also showed that reactivating the cleaning system is possible. To do this, they used an experimental molecule called CA77.1, designed to activate precisely this natural process of protein recycling inside cells, improving their ability to eliminate waste products. For Professor Boya, who runs the University of Fribourg’s Autophagy Lab, the results are encouraging, “Using experimental models, we demonstrated that activating this mechanism makes it possible to reduce the accumulation of waste, limit inflammation, and slow vision deterioration in two different models.”

With the help of Professor Jörn Dengjel of the University of Fribourg’s Department of Biology and other collaborators, Professor Boya carried out experiments on cells of patients suffering from AMD. The experiments indeed confirmed these observations. When the natural “cleaning” mechanism is strengthened, cells function in a more balanced way and are better able to withstand stress.

New therapies in sight
Rather than tackling only the symptoms or one particular cause, it becomes possible to target a fundamental mechanism that is common to several eye conditions. Stimulating CMA either through genetic approaches or by the CA77.1 molecule, the researchers helped the cells eliminate their waste products and thus reduce their stress and improve their chances of survival.

These results could lead to developing treatments that can slow down or even prevent age-related vision loss, offering concrete hope to millions of people.

References

Chaperone‑mediated autophagy protects against retinal photoreceptor degeneration by modulating proteostasis of glucose metabolism enzymes. PNAS, 123(20), e2527503123. https://doi.org/10.1073/pnas.2527503123

Defective chaperone‑mediated autophagy in the retinal pigment epithelium of age‑related macular degeneration patients. EMBO Molecular Medicine, 17(12), 3472‑3495. https://doi.org/10.1038/s44321-025-00329-w