Scientists at the Jules Stein Eye Institute at the David Geffen School of Medicine at UCLA have uncovered a remarkable ability of certain retinal cells to rewire themselves as vision deteriorates in retinitis pigmentosa, a genetic condition leading to progressive blindness. This groundbreaking study, published in Current Biology, utilized mouse models to demonstrate that rod bipolar cells, neurons typically receiving signals from rods responsible for night vision, can form new functional connections with cones, which provide daytime vision, when their usual partners fail.
The discovery holds significant implications for millions affected by retinitis pigmentosa globally, a leading cause of inherited blindness. The disease often progresses slowly, and some patients maintain a surprising amount of usable vision into middle age. However, the mechanisms through which retinal circuits adapt to cell loss have remained largely unknown. Understanding these natural adaptation processes could pave the way for new treatments aimed at preserving vision.
Understanding the Study
The researchers focused on rhodopsin knockout mice, which model early retinitis pigmentosa where rod cells cannot respond to light, and degeneration occurs gradually. By making electrical recordings from individual rod bipolar cells, the team observed how these neurons behaved when deprived of their usual input. Additional mouse models lacking different components of rod signaling were employed to identify triggers for the rewiring process. These findings were corroborated with whole-retina electrical measurements.
In mice lacking functional rods, rod bipolar cells exhibited large-amplitude responses driven by cone cells instead of their normal rod inputs. These rewired responses displayed the expected electrical characteristics of cone-driven signals. Interestingly, this rewiring occurred specifically in mice with rod degeneration, but not in other models lacking rod light responses without actual cell death. This suggests that the degeneration process itself, rather than merely the absence of light responses or broken synapses, triggers cellular rewiring.
Complementary Findings
The findings complement previous research by the team in 2023, which showed that individual cone cells can remain functional despite severe structural changes in later disease stages. Together, these studies reveal that retinal circuits maintain function through various adaptation mechanisms at different stages of disease progression. This insight could help scientists identify new targets for preserving vision in patients with inherited retinal diseases.
Expert Insights
“Our findings show that the retina adapts to the loss of rods in ways that attempt to preserve daytime light sensitivity,” said senior author A.P. Sampath, Ph.D. of the Jules Stein Eye Institute. “When the usual connections between rod bipolar cells and rods are lost, these cells can rewire themselves to receive signals from cones instead. The signal for this plasticity appears to be degeneration itself, perhaps through the role of glial support cells or factors released by dying cells.”
Future Directions
One of the open questions is whether this rewiring represents a general mechanism used by the retina when rods die. The research team is currently exploring this possibility with other mutant mice carrying mutations to rhodopsin and other rod proteins known to cause retinitis pigmentosa in humans.
About the Study
Published in Current Biology (2025), the study titled “Photoreceptor degeneration induces homeostatic rewiring of rod bipolar cells” provides a detailed exploration of these adaptive processes. Read more about the study here.
Research Team and Funding
The research was conducted by Paul J. Bonezzi, Rikard Frederiksen, Annabelle N. Tran, Kyle Kim, Gordon L. Fain, and Alapakkam P. Sampath from the Department of Ophthalmology, Stein Eye Institute, David Geffen School of Medicine at UCLA. Paul J. Bonezzi and Rikard Frederiksen contributed equally to this work. The study was supported by the National Eye Institute of the National Institutes of Health USA and an unrestricted grant by Research to Prevent Blindness to the UCLA Department of Ophthalmology. The authors have no disclosures.
This development represents a significant step forward in understanding and potentially treating inherited retinal diseases, offering hope for improved therapeutic strategies that could one day preserve vision for those affected by retinitis pigmentosa.
