For decades, scientists believed that photoreceptors in the retina primarily relied on adjacent supporting cells, known as the retinal pigment epithelium (RPE), to remove waste products. The RPE is still responsible for removing the worn tips of photoreceptors every day, but a new discovery from the University of Oklahoma reveals that photoreceptors also perform much of their own internal housekeeping. This research cell death and disease.
Our study provides the first direct evidence that photoreceptors have a unique internal recycling system essential for their survival. Rather than relying solely on the RPE, photoreceptors use the cell’s recycling center, the lysosome, to recycle and degrade their own damaged proteins and cellular components. ”
Dr. Raju VS Rajala, first author, OU Professor of Medicine, Dean McGee Department of Ophthalmology and Biochemistry and Physiology.
Every time people open their eyes, millions of photoreceptors go to work converting light into signals that the brain can interpret. These cells are constantly active, require enormous amounts of energy, and continually produce damaged proteins and worn-out cellular components that must be removed. Without an efficient recycling system, this cellular waste accumulates, causing cellular dysfunction and ultimately cell death.
To understand how this process works, researchers removed an enzyme called PIKfyve from mice. Without it, the photoreceptor recycling system cannot function. Damaged proteins accumulate within cells and gradually degenerate photoreceptors, leading to progressive vision loss.
The research team also found that PIKfyve is important for the health of the RPE itself. In the absence of this enzyme, fat and cellular waste accumulate in these supporting cells, causing changes similar to those seen in age-related macular degeneration, one of the leading causes of vision loss in older adults.
“These discoveries change our understanding of retinal biology,” said Rajala. “Photoreceptors are not passive cells that rely entirely on the RPE for waste disposal. Instead, they have an active quality control system that continuously removes damaged proteins and maintains cell health.”
The discovery could have important implications for a number of inherited retinal diseases, which are often associated with problems in cells’ ability to remove damaged proteins. By identifying PIKfyve as a central regulator of this process, researchers discovered a promising new target for treatments designed to preserve vision before irreversible damage occurs.
This study also raises important safety questions in drug development. A drug called apilimod that blocks PIKfyve is currently being studied as a potential treatment for autoimmune diseases, certain cancers, neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), and viral infections such as COVID-19 and Ebola. While the drug may be beneficial for these conditions, the new findings suggest that inhibiting PIKfyve may interfere with the retina’s natural recycling system, and emphasizes the need to carefully evaluate potential effects on vision in future clinical trials, Dr. Rajala said.
sauce:
Reference magazines:
Rajala, A. Others. (2026). PIKfyve maintains endolysosomal function in photoreceptors and RPE cells and maintains retinal integrity. cell death and disease. DOI: 10.1038/s41419-026-08855-2. https://www.nature.com/articles/s41419-026-08855-2
