Ultrasensitive human TRPV1 channels for infrared light detection in blind human retina

Transient receptor potential vanilloid 1 (TRPV1) is a polymodal, nonselective cation channel that can be activated by capsaicin, noxious heat, protons, and other chemical or mechanical stimuli; it is a member of the TRPV subfamily within the broader TRP superfamily of ion channels. 

Rational design of a human TRPV1 mutant (Δ786–840) lowered its heat switch-on temperature to 41°C. The mutant was coupled with safe near infrared (NIR) microheating to activate retinal neurons at close-to-body temperatures.

This all-human, single-gene system avoids foreign proteins or nanoparticles and fits into a standard adeno-associated virus (AAV) vector. In blind human retina explants, brief NIR pulses evoked fast, intensity-graded spiking through the engineered channel.

This opsin-free strategy paves the way for infrared prosthetics that complement residual vision in macular diseases.

The design principle can extend to other TRP channels, expanding the toolkit for thermal neuromodulation.

https://www.cell.com/trends/biotechnology/fulltext/S0167-7799(25)00318-X

https://sciencemission.com/ultrasensitive-human-TRPV1-channels