Why retinal energy use matters in retinitis pigmentosa

Retinitis pigmentosa (RP) is a group of inherited retinal diseases in which rod photoreceptors—the cells that support vision in dim light—are often affected first. As rods become dysfunctional and die, people may experience night blindness and progressive loss of peripheral vision. Understanding the biology that keeps rods alive and functioning is therefore central to understanding RP.

A 2026 study in Science Advances provides a detailed look at how rods produce and use energy compared with other retinal neurons. The findings show that rods have an unusually demanding and distinct metabolic program: they depend on both aerobic glycolysis and oxidative phosphorylation (OXPHOS) to maintain their energy supply. The study also found that an RP-causing mutation increases lactate production in rods, while causing only subtle changes in other measured aspects of rod energy metabolism.

Two energy pathways, one highly demanding cell type

Cells make energy in the form of adenosine triphosphate, or ATP. This molecule powers essential activities, from maintaining cell structure to sending signals.

The researchers focused on two major ways cells process glucose:

  • Aerobic glycolysis converts glucose into lactate even when oxygen is available. This pattern is sometimes called the Warburg effect.
  • Oxidative phosphorylation, or OXPHOS, occurs in mitochondria and uses oxygen-dependent processes to generate ATP.

The retina has long been known to convert large amounts of glucose to lactate. However, it had not been clear how this metabolism differed among retinal cell types. Using two-photon fluorescence lifetime imaging and metabolic biosensors, the investigators compared healthy and diseased rod photoreceptors with two inner-retinal neuron populations: RBPMS-positive ganglion cells and calretinin-positive amacrine cells.

Their results identified rods as the main drivers of aerobic glycolysis in the retina. In contrast, the ganglion and amacrine cells examined relied primarily on OXPHOS. This demonstrates that retinal neurons do not all meet their energy needs in the same way.

Rods need glycolysis and OXPHOS

One of the study’s most important findings is that rods are not simply glycolytic cells. Although they are the leading source of aerobic glycolysis and lactate production, they also require OXPHOS to maintain ATP levels.

This dual dependency is especially relevant because rods are among the retina’s most metabolically active cells. They must continually support the processes needed for photoreception, including the demanding work of responding to light and maintaining their specialized outer segments. The new data indicate that disrupting either major energy pathway can threaten the ability of rods to sustain ATP.

The findings also suggest that rods can metabolize lactate. Lactate is often described as a metabolic byproduct, but this result points to a more complex role. Within the retina, lactate may participate in how energy is handled and exchanged rather than simply representing unused fuel.

What changed in an RP model?

The researchers also examined rods carrying a mutation that causes retinitis pigmentosa. These diseased rods produced more lactate than healthy rods. Yet, beyond this increase in lactate production, the measured changes in energy metabolism were subtle.

This is an important distinction. The results do not portray RP rods as having a complete collapse of energy production across all pathways. Instead, they reveal a detectable shift in metabolic behavior, particularly in lactate production, within cells that still retain a need for both glycolysis and OXPHOS.

For the RP community, this adds another layer to the understanding of rod vulnerability. Disease-causing mutations may influence not only the specific gene pathway involved, but also the broader metabolic environment in which rods must operate.

Relevance for treatment research

Current and emerging RP research includes approaches designed to address disease-causing genes, preserve surviving photoreceptors, or restore vision after substantial cell loss. This study does not test a treatment, but it offers foundational information that may help guide future work.

In particular, the results emphasize that rods should be considered metabolically distinct from inner retinal neurons. Strategies intended to protect rods may need to account for their reliance on both glucose processing through glycolysis and mitochondrial ATP production through OXPHOS. A change that appears beneficial for one retinal cell type may not have the same effect in another.

The observation of increased lactate production in RP rods also creates a specific question for future studies: whether this change is a harmful sign of disease stress, a compensatory response, or part of an effort by rods to preserve their energy balance.

Building a more precise picture of retinal disease

This research moves the field beyond viewing the retina as a single metabolic unit. It shows that rods, ganglion cells, and amacrine cells can use fundamentally different energy strategies despite sharing the same tissue environment.

For RP research, that cellular precision matters. Mapping how individual retinal cell types respond to genetic disease may help researchers identify the earliest biological changes in vulnerable rods and develop more targeted ways to study photoreceptor preservation. As imaging tools and metabolic biosensors continue to advance, they may reveal how energy use changes over the course of retinal degeneration—and how those changes relate to the survival of the cells that make vision possible.