The newly developed compounds mimic the function of photoreceptor cells, which deteriorate in blinding diseases such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP).
In many blinding retinal diseases, the cells that first detect light disappear while much of the neural machinery behind them survives. That preserved circuitry has created an opportunity for researchers to restore light sensitivity without replacing the damaged cells themselves.
Age-related macular degeneration (AMD) and retinitis pigmentosa (RP) are among the diseases in which photoreceptors, the retina’s light-sensing cells, gradually deteriorate and die. Together, conditions involving photoreceptor degeneration affect about 200 million people worldwide and are leading causes of visual impairment and blindness. Vision loss also reduces independence and quality of life while contributing more than US$400 billion annually in healthcare expenses and lost productivity.
Even after photoreceptors are lost, much of the retinal network that normally carries visual information toward the brain remains functional. The problem is that this circuitry no longer receives the light signals needed to begin visual processing.
Researchers have pursued several ways to reactivate it. Gene therapy can help only a small proportion of patients whose blindness results from specific mutations. Electronic retinal implants are costly and invasive, and users require extensive training. Optogenetics and light-responsive drugs have reached clinical testing, with early drug trials producing encouraging safety findings, but restoring high-quality vision under ordinary lighting remains difficult.
Drugs reactivate surviving retinal cells
A consortium led by the Institute for Bioengineering of Catalonia (IBEC) has developed photoswitchable small molecule drugs that restored important visual responses in animal models of blindness. The findings were published in the Journal of the American Chemical Society (JACS).
The compounds are designed to perform part of the job normally handled by photoreceptors. Researchers delivered them through injections into the eye, similar to other ophthalmic treatments, and through eye drops. Neither approach requires an implanted device or genetic modification.
Early results also indicated promising safety profiles, supporting further investigation of the molecules as possible candidates for future vision restoration treatments.
“These molecules do not cure blindness, because they do not address the cause of photoreceptor degeneration. But they are remarkably effective at restoring sight, and they do so using a very simple and potentially patient-friendly approach”, explains Pau Gorostiza, ICREA Research Professor at IBEC, leader of the Nanoprobes and Nanoswitches group, member of CIBER-BBN and co-leader of the study.
“Our goal was to restore vision using a molecular mechanism that is as close as possible to how the healthy retina works,” says Rosalba Sortino, former PhD student at the University of Barcelona, currently a postdoctoral researcher in Gorostiza’s group at IBEC and co-first author of the study. “Instead of bypassing retinal processing, we aimed to reactivate it right at the same level of the retinal circuit as the lost photoreceptor cells.”
The findings build on more than ten years of work. The project brought together Pedro de la Villa’s group at the University of Alcalá (UAH) and scientists from the Institut de Química Avançada de Catalunya (IQAC-CSIC), the University of Barcelona (UB), the Institute Ramón y Cajal of Health Research (IRYCIS), the Autonomous University of Barcelona (UAB), and the Fundació Eduard Soler.
Eye drops restore light responses in animals
The strategy uses photopharmacology, a method that allows light to switch a drug’s activity on and off. Researchers modify the drug by attaching a molecular switch that changes its behavior when illuminated, making its effects reversibly controllable with light.
Using this principle, the consortium created a family of compounds called prosthe6. The drugs target ON bipolar neurons, retinal cells that normally receive information from photoreceptors.
In blinded zebrafish larvae, a common model for measuring visual acuity, prosthe6 restored saccadic eye movements (optokinetic reflex). The compounds also restored an instinctive light avoidance response in mouse models of age-related macular degeneration and retinitis pigmentosa.
Mice with normal vision naturally favor darkness and avoid brightly illuminated spaces. Blind mice no longer distinguish between the two environments and move freely between light and dark areas because they cannot detect the difference.
After receiving prosthe6, the blind mice again displayed a spontaneous preference for darkness. The behavior indicated that they could detect light and use that information to guide their movements.
No training was required, and the response appeared under illumination comparable to indoor lighting or an overcast day. This suggested that the treatment restored functional light perception under ordinary conditions rather than only under unusually intense light.
Two compounds, prosthe6-12 and prosthe6-15, produced especially encouraging results. Visual responses returned following injections into the eye and after the drugs were delivered topically as eye drops.
Molecules replace lost photoreceptor signals
Prosthe6 works through ON bipolar cells, which sit downstream from photoreceptors in the retinal circuit. These cells usually receive the initial light-related signals generated by photoreceptors and pass that information deeper into the visual system.
“In healthy vision, ON bipolar cells play a key role in passing on information about the presence of light to the rest of the visual circuit. In degenerative eye diseases, although the photoreceptors are lost, much of this underlying circuitry remains intact but inactive. This creates a major therapeutic opportunity,” explains de la Villa, co-leader of the study.
The compounds target a protein (mGlu6) within this surviving network. When light reaches the eye, prosthe6 molecules change shape and trigger activity inside the retina that resembles the signaling normally initiated by photoreceptors.
In this sense, the drugs function as “molecular prostheses.” They substitute for signals from the missing cells, allowing preserved retinal circuits to process light again without an electronic implant or genetic intervention.
The compounds were also designed to respond to normal visible or white light. Unlike some optogenetic approaches, they do not require devices that intensify or modify illumination. Their small, water-soluble structures allow them to react under daylight or typical indoor lighting rather than specialized, high-intensity sources.
Human testing has not begun
The work follows the publication of the first clinical trial involving a photopharmacological drug intended to restore vision (which targets an unrelated protein). That trial provides evidence that the broader strategy is beginning to move from laboratory research toward patient testing.
Prosthe6 itself remains at an earlier stage. The technology is patent-protected, and researchers are continuing to assess safety and develop formulations that could prolong the period of visual rehabilitation.
The group is also working with Eyelumina, a spin-off company being formed to attract investment for translational research and eventual clinical trials.
“Turning this into a therapy is a long and laborious process,” says Gorostiza. “But the results show that there is a realistic possibility of restoring high-quality vision with drugs, non-invasively, reversibly and with a mechanism that is independent of the specific retinal disorder or genetic mutation to reach a majority of patients.”
Whether the benefits observed in animals will translate to people remains unknown. If future human studies are successful, however, this drug-based approach could provide a more accessible and affordable option than current vision restoration technologies, particularly for people with advanced retinal degeneration who have no effective treatment.
Reference: “Restoration of Saccadic Eye Movements and Visually Guided Behavior in Ambient White Light with Photoswitchable Small Molecules” by Rosalba Sortino, Aleix González-Díez, Santiago Milla-Navarro, Joaquín Martínez-Tambella, Víctor Paleo-García, Eric Calatayud, Paula de Saralegui, Ekin Opar, Àlvar Claparols, Josecarlo A. Quintanilla, Xavier Martínez-Soler, Fabio Riefolo, Carlo Matera, Jordi Hernando, Alexandre M. J. Gomila, Gerard Pérez-Batlle, Carles Pereira, Núria Camarero, Carme Serra, Xavier Gómez-Santacana, Amadeu Llebaria, Xavier Rovira, Pedro de la Villa and Pau Gorostiza, 15 July 2026, Journal of the American Chemical Society.
DOI: 10.1021/jacs.5c18611
This research received seed funding from the patients’ foundation Fundaluce (2016), CaixaHealth (Drug4sight, 100010434), the Government of Catalonia (Innovadors, Producte, and Peris programs), and CIBER-BBN (valorization program).
Disclosure: This research is also part of Rosalba Sortino’s doctoral thesis. She was awarded the Extraordinary Doctoral Prize for the 2023–24 academic year by the University of Barcelona (UB) for her thesis, which she presented at the Faculty of Pharmacy and Food Sciences.
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