Nobel Prize awarded for optogenetics, as therapy for inherited blindness is tested

From light-sensitive, single-celled algae to using lasers to trigger mouse whisker movements, the 2026 Nobel Prize in Physiology or Medicine recognises the discovery of light-gated ion channels and their applications in optogenetics to study brain function.

Professor Peter Hegemann (Humboldt University of Berlin, Germany), Professor Georg Nagel (University of Würzburg, Germany) and Professor Karl Deisseroth (Stanford University, California) were jointly awarded the prize. Professors Hegemann and Nagel were recognised for characterising light-gated ion channels, while Professor Deisseroth developed optogenetics to control nerve-cell activity with light. Separately, a clinical study published in the New England Journal of Medicine tested a gene therapy using the same underlying technology in people with advanced vision loss.

'We've had anatomical maps and correlations, but now we have a tool that can provide cause-and-effect relationships so we can get a functional map of the brain' explained Professor Anna Wedell, an associate member of the Nobel Committee for Physiology or Medicine.

A channelrhodopsin is a protein that sits in the membrane of a cell. Exposure to light changes its shape, opening a channel that allows charged ions to cross the membrane and alter the cell's electrical activity. These light-sensitive channelrhodopsins were first discovered in single-celled algae. Researchers isolated the associated gene and expressed it in frog egg cells to investigate the protein's electrophysiological properties.

Because the light-sensitive protein is encoded by a single gene, researchers can introduce it into other organisms and use light signals precisely controlled in time and space to activate it. By expressing the channelrhodopsin gene in mice, Professor Deisseroth and colleagues showed that shining light on a relevant area of the brain could trigger whisker movements. The Nobel Committee highlighted how optogenetics enables researchers to stimulate nerve cells in animal models and investigate how their activity relates to behaviour

In the clinical study, led by Professor José-Alain Sahel of the University of Pittsburgh, researchers delivered the gene for the light-sensitive protein ChrimsonR to the eye using an adeno-associated viral vector. The treatment was tested in ten people with advanced retinitis pigmentosa, an inherited condition that causes degeneration of the light-detecting cells in the retina. Normally, photoreceptors detect light and transmit signals through retinal cells to the brain. In advanced retinitis pigmentosa, these cells have degenerated, so the treatment aims to make surviving retinal ganglion cells sensitive to light instead. To help activate ChrimsonR, patients wear special goggles that convert visual information from their surroundings into red-light signals.

This work builds on the first optogenetic treatment in a person with retinitis pigmentosa (see BioNews 1097). The new study included the previously reported participant and nine additional patients. Four participants completed five years of follow-up, while follow-up periods varied for the others; two participants withdrew from the study.

In terms of safety, five participants had increased levels of antibodies against the injection virus, but no systemic adverse events were considered related to the treatment or injection. Improvements in vision were modest, with six of the ten participants showing a clinically meaningful increase in light sensitivity. Some patients also showed improved accuracy in detecting and locating objects, such as a notebook on a table, but they did not regain detailed vision.

'These results show that even in people with profound vision loss, the visual system retains a remarkable capacity to process new information,' said Professor Sahel.

In an accompanying perspective in the New England Journal of Medicine, Nobel laureate Professor Deisseroth discusses the clinical study and the science behind it. He suggests that newer, more light-sensitive channelrhodopsins could improve vision restoration. Further research is needed to assess the treatment's safety and effectiveness.