How a Single Ion Channel Can Disrupt Vision: New Insights Into Night Blindness and Retinal Degeneration

A new study from Ritsumeikan University has revealed that the loss of just one ion channel,
TRPM1, is enough to trigger persistent rhythmic electrical activity (oscillations) in
the retina. These oscillations act like “neural noise” and are seen in conditions such as
congenital stationary night blindness (CSNB) and retinitis pigmentosa (RP).

For patients, this neural noise can interfere with the normal transmission of visual information to the brain,
contributing to degraded, unstable, or even distorted vision.

The findings also highlight a crucial message for the future of vision-restoration therapies:
it’s not enough to restore light-sensitive cells—we must also stabilize the retinal circuitry
that processes visual signals.

What Did the Researchers Discover?

The team studied mouse models in which specific genes involved in retinal signaling were knocked out. Both
Trpm1 and mGLuR6 are associated with congenital stationary night blindness and
are crucial for ON bipolar cell function, which helps the retina detect increases in light.

Interestingly, while both gene knockouts affect vision, only the Trpm1 knockout (KO) mice showed
strong, spontaneous rhythmic activity in retinal ganglion cells (RGCs)—the cells that send visual information
from the eye to the brain.

Using whole-cell clamp recordings and computational modeling, the researchers found that:

• Inhibitory and excitatory inputs oscillate in opposite phases, creating “anti-phase” activity between ON and OFF pathways.
• The oscillations come from a disrupted circuit involving rod bipolar cells (RBCs) and AII amacrine cells (AII ACs).
• Blocking specific synaptic or gap junction pathways stopped the oscillations entirely.

Structural Changes That Destabilize the Retina

The electrical instability also coincided with physical remodeling of the retina. In Trpm1 KO mice:

• Rod bipolar cell axon terminals were smaller and mispositioned.
• Patterns resembled changes found in rd1 mice, a model of retinitis pigmentosa.
• Rod bipolar cells were more hyperpolarized, weakening their communication with AII amacrine cells.

These changes create a self-sustaining loop of rhythmic activity that interferes with real visual signals.

Why These Oscillations Matter for Vision

Pathological retinal oscillations can:

• Reduce visual clarity and contrast
• Distort motion or shape perception
• In severe cases, contribute to hallucinatory or false visual experiences

Computational models confirmed that even small reductions in bipolar cell output can destabilize retinal circuits.

Key Facts

• TRPM1 Loss Drives Oscillations: Eliminating TRPM1 disrupts ON-bipolar cell signaling.
• Circuit Instability: Weak RBC–AII AC coupling and anti-phase signaling produce rhythmic “neural noise.”
• Shared Mechanism in CSNB & RP: Similar oscillations appear in both diseases.
• Therapeutic Implication: Future therapies must also stabilize retinal circuitry.

Implications for Future Vision Restoration Treatments

Advances such as gene therapy, optogenetics, stem-cell photoreceptors, and retinal implants hold enormous
promise. But this research shows that:

Restoring photoreceptors alone may not restore clear vision.

If the retina remains oscillatory, patients could regain light perception but still experience distorted or
unreliable vision. Stabilizing these circuits will be essential for next-generation therapies.

What This Means for Patients at Belmont Eye Center

For individuals with congenital stationary night blindness, retinitis pigmentosa, or other inherited retinal
conditions, these findings offer new understanding of why vision becomes unstable and how future treatments may
evolve.

Our team closely follows these developments to better guide patients as new therapeutic options emerge.