When the Eye’s Recycling System Fails
Dr. Nayiar Shahid - 25 February 2026
Dr. Jen Hocking
Every time you open your eyes, millions of cells work together to let you see clearly. At the back of your eye sits the retina, a thin layer of tissue that detects light and turns it into signals your brain can understand. But vision isn’t just about sensing light. Retinal cells must constantly clean up and recycle their own waste to stay healthy.
A new study from Dr. Hocking’s research group, published in Experimental Eye Research, reveals what happens when a key enzyme involved in this recycling system stops working.
Two important cell types keep the retina functioning. First are photoreceptors (rods and cones), which detect light. Just behind them are retinal pigment epithelium (RPE) cells. These support photoreceptors by delivering nutrients, absorbing excess light, and clearing away worn-out cellular components.
Photoreceptors shed damaged pieces every day. The RPE acts like a 24/7 recycling crew, swallowing and breaking down this cellular waste. If that system fails, debris builds up, and vision can begin to decline.
Inside these cells is a transport and cleanup network called the endolysosomal pathway. It consists of tiny membrane-bound compartments that move and digest cellular material. One of the digesting molecules, an enzyme known as Fab1, YOTB, Vac1, EEA1 zinc finger-containing phosphoinositide kinase - but most people call PIKfyve (pronounced “pick five”) - helps control this pathway. It modifies special fat molecules on cell membranes, guiding when these compartments move, merge, or break down their contents.
To understand PIKfyve’s role, the research team used zebrafish, which have retinas similar to humans. They reduced PIKfyve activity in two ways: by using CRISPR gene editing technology to delete areas in the pikfyve gene, required for proper function and by treating the fish with a drug called apilimod, which blocks the enzyme.
In both cases, problems appeared quickly.
RPE cells became swollen and filled with large bubble-like structures called vacuoles. These contained markers of late-stage recycling compartments, suggesting that waste was being collected but not properly broken down.
Photoreceptors were also affected. Large vacuoles also formed inside the cells, even though their outer light-detecting structures initially looked mostly normal. This showed that internal maintenance problems began before obvious structural damage appeared.
To test how vision was affected, they used electroretinography (ERG), a test that records the retina’s electrical response to light. Fish with early PIKfyve disruption showed almost no response. Fish treated later still responded to light, but their signals were weaker and slower.
In other words, vision declined even when the retina still looked mostly intact under the microscope. Healthy recycling inside cells is essential for proper function.
The researchers also noticed changes in melanosomes, pigment-filled structures in RPE cells that absorb stray light and protect the retina. When PIKfyve was blocked, pigment levels dropped, and the tissue became more fragile.This tends to fit with the clinical spectrum in which changes in the PIKFYVE gene have been directly linked to eye diseases, such as Fleck corneal dystrophy, congenital cataracts, and may contribute to age-related macular-degeneration.
However, that is not the end of the story for PIKfyve. That's because PIKfyve inhibitors are being investigated as a treatment for diseases such as cancer, neurological conditions, and even COVID-19. Yet, as this research work suggests, any therapeutic use will need to consider potential side effects carefully. Until we know the potential toll resulting from blocking this enzyme’s activity in sensitive tissues like the retina, we cannot be confident that such inhibitors would provide more benefit than risk.
The study highlights an important lesson: tiny enzymes inside cells can have enormous effects. In delicate tissues like the retina, where constant renewal is required, even small disruptions to the recycling system can quickly threaten vision. It also reminds us that we should always look closely at cell biology mechanisms in order to fully understand the impact of what may seem like a good idea in a completely different context.