Scientists at the Jules Stein Eye Institute at the David Geffen School of Medicine at UCLA have unveiled a groundbreaking discovery about retinal cells’ ability to rewire themselves as vision deteriorates. This finding, published in Current Biology, focuses on retinitis pigmentosa, a genetic eye disease that leads to progressive blindness. The research reveals that rod bipolar cells, which typically receive signals from rods responsible for night vision, can form new connections with cones, the cells that facilitate daytime vision. This adaptation occurs when their usual partners cease to function, offering new insights into potential treatments for preserving vision.
The announcement comes as retinitis pigmentosa remains a leading cause of inherited blindness, affecting millions globally. While the disease often progresses slowly, with some patients retaining significant vision into middle age, the mechanisms behind retinal circuit adaptation to cell loss have remained largely unexplored. This study sheds light on these natural adaptation processes, potentially guiding future therapeutic strategies.
Understanding the Study
Researchers conducted their study using rhodopsin knockout mice, which serve as models for early retinitis pigmentosa. In these mice, rod cells are unable to respond to light, leading to gradual degeneration. By making electrical recordings from individual rod bipolar cells, the team observed how these neurons behaved when deprived of their usual inputs. Additional mouse models lacking components of rod signaling helped determine the triggers for the rewiring process.
The findings were supported by whole-retina electrical measurements, demonstrating that rod bipolar cells in mice with non-functional rods exhibited large-amplitude responses driven by cone cells. These responses mirrored the electrical characteristics expected of cone-driven signals. Importantly, the rewiring was specific to mice experiencing rod degeneration, indicating that the process is triggered by degeneration itself rather than simply the absence of light responses or broken synapses.
Implications for Future Treatments
The study’s results complement previous research by the team, which showed that individual cone cells could remain functional despite severe structural changes in later stages of the disease. Together, these findings suggest that retinal circuits employ different adaptation mechanisms at various stages of disease progression. This understanding could be pivotal in identifying new targets for preserving vision in patients with inherited retinal diseases.
“Our findings show that the retina adapts to the loss of rods in ways that attempt to preserve daytime light sensitivity in the retina,” said senior author A.P. Sampath, Ph.D. “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.”
Exploring Broader Applications
One of the open questions is whether this rewiring represents a general mechanism employed by the retina when rods die. The research team is currently investigating this possibility using other mutant mice with mutations in rhodopsin and other rod proteins known to cause retinitis pigmentosa in humans. This exploration could reveal whether similar adaptive mechanisms occur across different genetic mutations, potentially broadening the scope of therapeutic interventions.
About the Study
The study, titled “Photoreceptor degeneration induces homeostatic rewiring of rod bipolar cells,” was published in Current Biology (2025). For more details, the full text is available at Current Biology.
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. Notably, Paul J. Bonezzi and Rikard Frederiksen contributed equally to this work.
This work was supported by the National Eye Institute of the National Institutes of Health USA (EY36811 and EY01844) and an unrestricted grant by Research to Prevent Blindness to the UCLA Department of Ophthalmology. The authors have no disclosures.
As research continues, the hope is that these insights will pave the way for new therapies that can slow or even halt the progression of vision loss in retinitis pigmentosa, offering hope to millions affected by this debilitating condition.
