Ritsumeikan University researchers uncover how TRPM1 deficiency causes abnormal retinal oscillations

Abnormal rhythmic electrical signals in the retina are a hallmark of several vision disorders, but their origins have remained unclear. Researchers have discovered how the loss of the TRPM1 ion channel disrupts communication between retinal cells, triggering oscillations that distort visual signaling. Oscillations observed in Trpm1 knockout mice are strikingly similar to those found in retinitis pigmentosa–model mice, revealing a common generative mechanism for these abnormal rhythmic signals in retinal diseases.

Rhythmic electrical activity in the retina (known as pathological oscillations) has been observed in several eye diseases, including congenital stationary night blindness (CSNB) and retinitis pigmentosa (RP). These oscillations interfere with the normal transmission of visual information to the brain, often causing degraded or distorted perception. Although scientists have long known that such oscillations occur in retinal ganglion cells (RGCs), the neurons responsible for sending visual signals to the brain, the cellular mechanism that drives this rhythmic activity has remained elusive.

In a recent study published online in The Journal of General Physiology on October 16, 2025, led by Mr. Sho Horie, a PhD candidate, from the Graduate School of Pharmacy, Ritsumeikan University, Japan, along with Professor Katsunori Kitano, Professor Masao Tachibana, and Professor Chieko Koike, from Center for Systems Vision Science, Ritsumeikan University, revealed that the loss of a single ion channel—TRPM1—sets off a cascade of changes that lead to persistent oscillations in the retina. Their findings not only illuminate the cellular basis of CSNB but also identify a common mechanism underlying retinal degenerative conditions, such as RP.

TRPM1, a visual signal transduction channel found in retinal ON bipolar cells, is regulated by the metabotropic glutamate receptor, mGluR6. The genes associated with these channels (Trpm1 and mGluR6) are known to cause CSNB when mutated, yet they produce subtly different effects on retinal circuitry.

“Most of the phenotypes of the respective gene knockout mice are coincidental, but only the Trpm1 knockout (KO) mouse retina has spontaneous oscillation. Hence, we tried to figure out the difference between Trpm1 and mGluR6 KO mice,” explains Mr. Horie.

Using whole-cell clamp recordings and computational modeling, the team examined how TRPM1 loss alters retinal signaling. They found that in Trpm1 KO mice, inhibitory and excitatory inputs to RGCs oscillate in opposite phases, creating anti-phase rhythmic activity between OFF and ON pathways. Blocking specific synaptic and gap junction pathways silenced these oscillations, pinpointing the source to a disrupted circuit involving rod bipolar cells (RBCs) and AII amacrine cells (ACs).

The researchers also observed physical remodeling of the retina: the axon terminals of RBCs in Trpm1 KO mice were smaller and mispositioned, similar to changes seen in retinal degeneration (rd1) mice, a model for the degenerative disease, RP. These structural abnormalities correlated with a hyperpolarized resting potential in RBCs, weakening their communication with ACs.

“Under certain pathological conditions, RGCs can display spontaneous oscillatory activity,” notes Prof. Koike. “This ‘noise’ disrupts visual information processing and can cause hallucinations. Our study reveals why such oscillations occur in Trpm1 KO mice and suggests that the same mechanism drives them in degenerative diseases like RP.”

The researchers were able to replicate the oscillatory firing patterns seen experimentally by incorporating these structural and electrical changes into a computational model. The model confirmed that reduced synaptic strength between RBCs and ACs, combined with hyperpolarization of ON bipolar cells, is sufficient to trigger pathological rhythmic firing.

Prof. Kitano adds, “Our simulations show that even small reductions in bipolar cell output can destabilize retinal circuits, leading to oscillations that mask real visual signals.”

The study provides critical insight into how disruptions in TRPM1-dependent signaling can lead to neural noise across different retinal pathologies. Importantly, it suggests that therapies restoring vision (such as regenerative medicine or optogenetic treatment) should also address these oscillations to ensure patients regain clear vision, not distorted or hallucinatory perception.

The team hopes their findings will pave the way for new therapeutic approaches to stabilize retinal activity and improve outcomes in vision restoration treatments.

Title of original paper: A mechanism for pathological oscillations in mouse retinal ganglion cells in a model of night blindness
Journal: Journal of General Physiology
DOI: 10.1085/jgp.202413749

About Mr. Sho Horie from Ritsumeikan University, Japan

Mr. Sho Horie is a graduate student at the Graduate School of Pharmacy, Ritsumeikan University, and a member of the Laboratory for Systems Neuroscience and Developmental Biology, headed by Professor Chieko Koike. He is also a former Ritsumeikan Advanced Research Academy (RARA) Student Fellow, and his research focuses on retinal signal processing, including the role of the TRPM1 ion channel.

About Professor Chieko Koike from Ritsumeikan University, Japan

Dr. Chieko Koike is a Professor at the College of Pharmaceutical Sciences, Ritsumeikan University and Director of the Center for Systems Vision Science. She completed her doctoral studies at the University of Shizuoka. She pursued doctoral research fellowships at Boston Children’s Hospital (Harvard Medical School) and other institutes. She was an instructor at the Osaka Bioscience Institute and also held research positions at JST PRESTO, which she maintained even after moving to Ritsumeikan University as an Associate Professor. Her research investigates the cellular and molecular mechanisms of retinal signal processing and related disorders, aiming to develop therapies for vision restoration and degenerative eye diseases.

Funding information

This work was supported by the Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research (Grants Nos. 24H00747, 22KK0137, 19H01140, and 24390019), Takeda Science Foundation, the Kobayashi Foundation, JST PRESTO, and R-GIRO.