Researchers Discover Hidden ‘Recycling System’ That Helps Keep Vision Cells Healthy

OKLAHOMA CITY – For decades, scientists believed that photoreceptors in the retina relied primarily on neighboring support cells, known as the retinal pigment epithelium (RPE), to remove waste. While the RPE is still responsible for clearing away the worn-out tips of photoreceptors each day, new findings from the University of Oklahoma reveal that photoreceptors also perform much of their own internal housekeeping. The study is published in Cell Death & Disease.

“Our study provides the first direct evidence that photoreceptors possess their own internal recycling system that is essential for their survival. Instead of relying solely on the RPE, photoreceptors recycle and break down their own damaged proteins and cellular components using lysosomes, the cell’s recycling centers,” said lead author Raju V.S. Rajala, Ph.D., an OU College of Medicine professor in the Dean McGee Department of Ophthalmology and Department of Biochemistry and Physiology.

Every time people open their eyes, millions of photoreceptors go to work converting light into signals the brain can interpret. Because these cells are constantly active and require tremendous amounts of energy, they continuously produce damaged proteins and worn-out cellular components that must be removed. Without an efficient recycling system, this cellular waste builds up, causing the cells to malfunction and eventually die.

To understand how this process works, researchers removed an enzyme called PIKfyve in mice. Without it, the photoreceptors’ recycling system broke down. Damaged proteins accumulated inside the cells and the photoreceptors gradually degenerated, leading to progressive vision loss.

The team also found that PIKfyve is critical for the health of the RPE itself. When the enzyme was absent, fats and cellular waste accumulated in these support cells, producing 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,” Rajala said. “Photoreceptors are not passive cells that depend entirely on the RPE for waste disposal. Instead, they possess an active quality-control system that continuously removes damaged proteins and maintains cellular health.”

The findings may have important implications for many inherited retinal diseases, which are often linked to problems with cells’ ability to clear away damaged proteins. By identifying PIKfyve as a central regulator of this process, the researchers have uncovered a promising new target for therapies designed to preserve vision before irreversible damage occurs.

The research also raises important safety questions for drug development. A drug called Apilimod, which 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 prove beneficial for those conditions, the new findings suggest that inhibiting PIKfyve could interfere with the retina’s natural recycling system, highlighting the need to carefully evaluate potential effects on vision during future clinical testing, Rajala said.

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About the project

The paper, “PIKfyve preserves endolysosomal function in photoreceptors and RPE cells to maintain retinal integrity,” is at https://www.nature.com/articles/s41419-026-08855-2#Fun. The research was funded by the National Institutes of Health, Retinal Research Foundation, Presbyterian Health Foundation and Research to Prevent Blindness, Inc.

About the University of Oklahoma

Founded in 1890, the University of Oklahoma is a public research university with campuses in Norman, Oklahoma City and Tulsa. As the state’s flagship university, OU serves the educational, cultural, economic and health care needs of the state, region and nation. In Oklahoma City, the OU Health Campus is one of the nation’s few academic health centers with seven health profession colleges located on the same campus. The OU Health Campus serves approximately 4,000 students in more than 70 undergraduate and graduate degree programs spanning Oklahoma City and Tulsa and is the leading research institution in Oklahoma. For more information about the OU Health Campus, visit www.ouhsc.edu.