A consortium led by the Institute for Bioengineering of Catalonia (IBEC) has developed a new class of photoswitchable drugs that restored functional vision in completely blind mice — without surgery, genetic modification, or implanted devices. The compounds can be administered as simple eye drops and work under normal indoor lighting.
Published in the Journal of the American Chemical Society (JACS), the research introduces prosthe6, a family of small-molecule compounds that take over the role of dead photoreceptor cells by targeting a specific protein (mGlu6) in the retina's preserved ON bipolar neurons.
The Problem: 200 Million People Worldwide
Blinding diseases caused by photoreceptor degeneration — including age-related macular degeneration (AMD) and retinitis pigmentosa (RP) — affect 200 million people globally. Current treatments are limited: gene therapy works only for patients with specific mutations, and electronic retinal prostheses are invasive, expensive, and require extensive training.
In many of these conditions, the downstream retinal circuitry remains intact and functionally viable, but no longer receives light signals. This preserved but inactive circuitry represents a therapeutic opportunity.
How Prosthe6 Works
The prosthe6 compounds use photopharmacology — drug activity reversibly controlled by light. A molecular light switch is added to the compound's chemical structure, allowing pharmacological action to be toggled with visible light.
When administered to the eye (by injection or as eye drops), the molecules bind to mGlu6 receptors on ON bipolar neurons. When ambient light enters the eye, the molecules change shape, triggering retinal signals that closely mimic natural photoreceptor function. The drugs essentially act as "molecular prostheses" — replacing the signaling role of cells that have degenerated.
Critically, the compounds work under ordinary indoor or overcast daylight — no intense or specialized light sources required, unlike optogenetics approaches.
Results in Blind Mice
Two lead compounds, prosthe6-12 and prosthe6-15, showed particularly striking results:
In blind mice with age-related macular degeneration and retinitis pigmentosa models, treatment restored innate light-avoidance behavior. Healthy mice naturally prefer dark spaces and avoid bright light — a behavior that depends entirely on functional vision. After treatment, blind mice once again showed spontaneous preference for dark areas, indicating they could perceive light and use it to guide behavior.
This recovery occurred without any training and under normal ambient light levels — a key advance over previous approaches that required high-intensity light stimulation.
The compounds also restored saccadic eye movements (optokinetic reflex) in blinded zebrafish larvae, a standard model for measuring visual acuity.
From Lab to Clinic
The prosthe6 technology is protected by a patent, and researchers are now evaluating safety and formulation for extended visual rehabilitation. A spin-off company, Eyelumina, is being formed to secure investment for translational development and future clinical trials.
"Turning this into a therapy is a long and laborious process," says Pau Gorostiza, the study's co-leader at IBEC. "But the results show that there is a realistic possibility of restoring high-quality vision with drugs, noninvasively, reversibly and with a mechanism that is independent of the specific retinal disorder or genetic mutation."
The work follows the first clinical trial of a photopharmacological drug for vision restoration (targeting a different protein), suggesting the broader approach is moving toward human applications.
Reference: Restoraction of saccadic eye movements and visually guided behavior in ambient white light with photoswitchable small molecules, J. Am. Chem. Soc. (2026). DOI: 10.1021/jacs.5c18611
