New research from the University of Oklahoma announced on July 29 reveals that photoreceptors in the retina possess their own internal recycling system to maintain cellular health and preserve vision. Previously, scientists believed these cells relied mainly on neighboring retinal pigment epithelium (RPE) support cells to remove waste, but the study shows photoreceptors are more self-sufficient than previously thought.
Photoreceptors are responsible for converting light into signals that the brain interprets as vision. Due to their constant activity and high energy demands, they frequently generate damaged proteins and worn-out components that require removal. Without an efficient internal recycling process, this waste accumulates, leading to cell malfunction and death.
Researchers studied mice in which an enzyme called PIKfyve was removed. The absence of PIKfyve disrupted the photoreceptors' ability to recycle damaged proteins, resulting in progressive degeneration of these cells and subsequent vision loss. The study also found that PIKfyve is essential for maintaining healthy RPE cells; its absence led to a buildup of fats and waste similar to changes seen in age-related macular degeneration.
"These discoveries change our understanding of retinal biology," said Rajala. "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 could impact future treatments for inherited retinal diseases linked to impaired protein clearance by identifying PIKfyve as a potential therapeutic target before irreversible damage occurs. The research also raises safety concerns regarding drugs such as Apilimod—which blocks PIKfyve—currently under investigation for various conditions including autoimmune diseases, cancers, neurodegenerative disorders like amyotrophic lateral sclerosis (ALS), and viral infections such as COVID-19 and Ebola.
Rajala said it will be important to carefully evaluate any effects on vision during future clinical testing involving drugs targeting PIKfyve.
