Retinal Neurons Rewire To Preserve Sight in Mice With RP

Scientists at the Jules Stein Eye Institute at the David Geffen School of Medicine at UCLA have found that certain retinal neurons in mice can rewire themselves in response to early stages of retinitis pigmentosa, a genetic disease that causes progressive vision loss. The findings, published in Current Biology, suggest that the retina retains a capacity for adaptation that may help preserve visual function during the early course of degeneration.

Retinitis pigmentosa disrupts the function of photoreceptor cells, beginning with the loss of rods that support night vision, and eventually affecting cones that mediate daytime vision. While the disease often progresses slowly, many questions remain about how the retina responds to cell loss over time. Understanding these adaptive mechanisms could help researchers identify new strategies for preserving sight.

Rod bipolar cells form new connections with cone cells

The researchers studied rhodopsin knockout mice, a model that mimics early retinitis pigmentosa by eliminating rod light responses while allowing slow degeneration. Using electrical recordings from individual rod bipolar cells – neurons that normally receive signals from rods – the team observed a notable change. In the absence of rod input, these cells began responding to cone signals, indicating that new, functional connections had formed between rod bipolar cells and cones.

This rewiring was specific to retinal degeneration. In additional mouse models where rods could not respond to light but did not degenerate, rod bipolar cells did not form new connections with cones. These findings indicate that degeneration itself – not simply loss of light sensitivity or synaptic disruption – triggers the plasticity.

Retinal circuits adapt differently over time

The results build on previous findings from the same group, which showed in 2023 that individual cones remain functionally active even after significant structural deterioration. Taken together, these studies suggest that the retina employs distinct mechanisms to maintain visual processing during different stages of disease.

Electrical measurements across the whole retina confirmed that the new cone-driven signals observed at the single-cell level were consistent with larger-scale retinal responses. These adaptations, while not restoring full vision, may allow for retention of some visual function during the disease’s early phases.

Implications for treatment of inherited retinal diseases

The study highlights how cellular plasticity in the retina may preserve daytime vision, even as night vision deteriorates. Identifying the molecular signals involved in this rewiring process could offer new therapeutic targets. These might include factors released by dying rod cells or activity in glial support cells that help facilitate new synaptic connections.

Future research will explore whether similar plasticity occurs in other genetic models of retinitis pigmentosa, particularly those involving different mutations in rod-specific proteins such as rhodopsin.

Reference: Bonezzi PJ, Frederiksen R, Tran AN, Kim K, Fain GL, Sampath AP. Photoreceptor degeneration induces homeostatic rewiring of rod bipolar cells. Current Biology. 2025. doi: 10.1016/j.cub.2025.05.057

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