Dying eyes circling themselves to save sight

When darkness begins to turn off patients with retinitis pigmentosa, its retinal phase is an amazing rescue mission.

UCLA scientists have found that neurons that usually have night vision can fully restore themselves to maintain daytime vision when their usual cellular partner begins to die. This biological adaptation is captured in real time using advanced recording techniques, which reveals how the eyes maintain function even in the progression of genetic blindness.

This finding challenges long-standing hypotheses about retinal degeneration and suggests that the eyes have complex self-healing mechanisms that can inspire new therapies about genetic blindness in millions of people around the world.

Neuro partnership error

In healthy eyes, rod sensors handle night vision, while cones manage daylight. Each type is connected to a specialized neuron called bipolar cells—the circular bipolar cells cooperate only with the rod, while the cone bipolar cells work with the cone. This arrangement seems to be fixed, just like a permanent dance partner.

But UCLA researchers found that something extraordinary happens when poles start to die in retinitis pigmentosa. Rod bipolar cells suddenly have no partner, don’t simply close. Instead, they perform dramatic cellular pivots, forming a completely new functional connection to the cone.

“Our findings suggest that the retina adapts to the loss of rods in a way that attempts to preserve the retinal’s daytime light sensitivity,” explains AP AP Sampath, senior writer at the Jules Stein Eye Institute. “When the usual connection between the rod bipolar cells and the rod is lost, these cells can be reconnected to receive the cone signal.”

Cell Detective Work

The team used a model of early retinitis pigmentitis, in which rod cells were unable to respond to light and slowly degenerated. They performed electrical recordings from single rod bipolar cells to eavesdrop on conversations with other neurons.

What they found was amazing. Rod bipolar cells in mice lacking functional rods showed large amplitude responses driven by cones rather than their normal rod input. The answer to rewiring is:

• Strong, electrically robust, matching expected cone drive signal
• Especially triggered by rod degeneration, not just broken connections
• Common enough to increase overall retinal sensitivity by 50%
• Functional similarity to normal cone bipolar cell response

Crucially, this rewiring did not occur in mice where the rod simply could not respond to light, or the rod-to-bipolar connection was broken but the rod was still healthy. Cell transformation requires actual pole death.

Death as a signal

“This plasticity signal appears to be degeneration itself, perhaps through the role of glial support cells or factors released by dying cells,” Sampath noted. This suggests that dying rods release molecular distress signals, prompting their former partners to seek new connections.

The findings build on the team’s 2023 work, where individual cones can remain functional even after severe structural changes in advanced disease. In summary, these studies show that retinal circuits maintain function through different adaptation mechanisms at various disease stages-rewiring of rod bipolar cells, which later resilient in the cone cells themselves.

In patients with retinitis pigmentosa, surprisingly useful vision is usually maintained in middle age despite the persistent degeneration, and this study provides the first clear explanation for the adaptability of the retinal. Instead of simply losing function and dying, the eyes actively reorganize themselves to protect any vision still can.

The team is now exploring whether this rewiring represents a general survival mechanism by studying other mouse models known to cause mutations in human retinitis pigmentosa. Understanding how to enhance or guide this natural plasticity could provide new avenues for millions of people facing genetic blindness.

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