Retinitis pigmentosa is a genetic disease that slowly damages the retina and affects roughly 1 in 3,500 to 1 in 4,000 people in the United States and Europe. It often starts with night blindness and then narrows side vision over years.
A new mouse study reports that the retina does not passively fade during early stages of this condition. Instead, it changes which cells talk to each other to keep daylight vision working longer.
What changes inside the retina
Alapakkam P. Sampath, Ph.D., of the Jules Stein Eye Institute at the David Geffen School of Medicine at UCLA, led the work.
The retina uses two main photoreceptors, rods for dim light and cones for daytime and color. Signals from rods are relayed by rod bipolar cells to downstream neurons, while cones use multiple cone bipolar cell types to carry daytime signals.
In the new work, the rod pathway’s relay neurons began taking input from cones once many rods were lost. That is a rerouting of signals inside a circuit that is normally kept separate in healthy eyes.
“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 A. P. Sampath, Ph.D..
Experimenting on the retina
The team used rhodopsin knockout mice, a model in which rod photoreceptors first stop responding to light and then gradually die.
Researchers recorded electrical signals from single rod bipolar cells in retinal slices to test whether those cells were now driven by cone inputs.
They also measured whole retina signals using an electroretinogram, a test that sums activity from many cells.
The photopic b-wave rose in a way consistent with stronger cone driven bipolar cell responses, that evaluates how bipolar cells and Müller glia contribute to this signal.
“When the usual connections between rod bipolar cells and rods are lost, these cells can rewire themselves to receive signals from cones instead,” said Sampath. The authors then looked for what event triggers that switch.
Why degeneration flips the switch
To separate causes, the group tested mice that lacked rod light responses but did not undergo rod death, and mice that lacked the normal rod to rod bipolar synapse. In those models, rod bipolar cells did not show strong cone driven responses.
Independent work shows that the synapse between rods and rod bipolar cells requires ELFN1, a cell adhesion molecule that helps create the primary rod pathway.
This background makes it notable that when rods disappear, the relay neurons appear to reach for new cone inputs rather than stay idle.
Patterns across the data suggest that degeneration itself signals circuits to reconfigure. The switch did not follow from silent rods alone, and it did not follow from a broken rod synapse in the absence of actual cell death.
Second thread from 2023
Another line of research reported that even after severe structural changes, cones and their pathways can still function.
That work showed degenerating cones retain the key ion channels needed to respond to light and keep useful output to later retinal stages.
Combine that result with the new rerouting and a picture emerges. Cones can still respond, and the inner retina can shift to listen to them, which helps explain why many people retain usable daytime vision well into adulthood.
Together, the studies point to stepwise adaptation. As rods fail, cone signals carry more of the load, and downstream neurons adjust their wiring to keep those signals moving.
What it could mean for patients
Retinitis pigmentosa is rare but not trivial in scale, and families often navigate decades of uncertainty.
The finding that circuits can sustain daylight vision by reconfiguring suggests a practical window for treatments that boost or stabilize cone function.
Such a window could matter for gene therapy, optogenetic strategies, or small molecules that increase cone sensitivity.
If inner retina neurons are already poised to pass on cone signals, preserving the remaining cone responses may translate into more real world sight.
Clinical tests already capture the mass signals that reflect bipolar cell activity. Tracking the b-wave under bright light could help scientists see whether a medicine or genetic therapy strengthens the rerouted pathway over time.
Limits and next steps
These results come from mice, and that matters. Human retinas share core circuitry but differ in ratios of rods and cones and in the way daytime signals are pooled, so translation will require careful testing.
The team plans to examine other mutations that cause rod loss to see if the same circuit shift appears.
If the pattern holds, it would support the idea that degeneration triggers a broader program of homeostatic plasticity in the retina that favors preserving daylight function.
The next challenge is to identify the signals that tell rod bipolar cells to change partners.
Clues point to glia and to factors released by dying cells, and those ideas can now be tested with interventions and noninvasive readouts in living tissue.
The study is published in Current Biology.
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