UCLA Researchers Uncover Retinal Cell Adaptation in Vision Loss

Scientists at the Jules Stein Eye Institute of the David Geffen School of Medicine at UCLA have made a significant discovery regarding retinal cells' ability to adapt when faced with vision deterioration caused by retinitis pigmentosa, a genetic disorder that leads to progressive blindness. In a groundbreaking study published in *Current Biology* on July 8, 2025, researchers utilized mouse models to explore how certain retinal neurons, specifically rod bipolar cells, can establish new functional connections with cone cells when their traditional partners cease functioning.

Retinitis pigmentosa affects millions globally and is a leading cause of inherited blindness, often progressing slowly. Despite some patients retaining usable vision into middle age, the mechanisms underlying retinal circuit adaptation to cell loss remain poorly understood. This study aims to illuminate these natural adaptive processes, potentially revealing novel targets for therapies designed to preserve vision.

In their research, the team leveraged rhodopsin knockout mice—models for early retinitis pigmentosa where rod cells fail to respond to light, resulting in gradual degeneration. Researchers conducted electrical recordings from individual rod bipolar cells to analyze their behavior when deprived of their usual input. They complemented these findings with whole-retina electrical measurements to solidify their observations.

The results showed that rod bipolar cells in the absence of functional rods exhibited robust responses driven by cone cells, indicating a remarkable rewiring capability. This adaptation was exclusive to mice with rod degeneration, suggesting that the rewiring process is initiated by the degeneration itself, potentially influenced by glial support cells or factors released by dying cells. This is a critical finding, as it implies that the retinal adaptation may occur through distinct mechanisms at various stages of disease progression, which could inform future treatments for inherited retinal diseases.

Dr. Alapakkam P. Sampath, the senior author and a professor at the Jules Stein Eye Institute, emphasized, "Our findings illustrate that the retina adapts to rod loss in ways that strive to maintain daytime light sensitivity. When normal connections between rod bipolar cells and rods are disrupted, these cells can rewire to receive signals from cones instead. This plasticity appears to be induced by degeneration itself."

One pertinent question arising from the study is whether this rewiring mechanism is a generalized response of the retina to rod cell death. The research team is currently investigating this hypothesis using various mutant mouse models carrying mutations associated with retinitis pigmentosa in humans.

The implications of this research are profound, not only in understanding the biological adaptability of retinal cells but also in the potential for developing new strategies to combat vision loss associated with inherited retinal diseases. As researchers continue to probe the complexities of retinal adaptation, the hope is to unlock new therapeutic avenues aimed at preserving vision for those afflicted by these debilitating conditions.

The study, titled "Photoreceptor degeneration induces homeostatic rewiring of rod bipolar cells," was funded by the National Eye Institute of the National Institutes of Health and received an unrestricted grant from Research to Prevent Blindness to the UCLA Department of Ophthalmology. The authors declare no competing financial interests.