In these diseases, the retina’s photoreceptor cells, which detect incoming light, gradually deteriorate and die. Yet much of the neural circuitry deeper within the retina can remain intact and capable of functioning. The problem is that, without photoreceptors, these surviving cells no longer receive the light signals needed to send visual information toward the brain.

That remaining retinal circuitry has become an important target for scientists trying to restore light sensitivity. Existing approaches include gene therapy, which is suitable for only a small fraction of patients with particular mutations, and electronic retinal prostheses, which can be invasive, costly, and require significant training. Optogenetics and light-responsive drugs have also entered clinical testing. Light-responsive drugs have produced encouraging safety results, but restoring high-quality vision under ordinary levels of illumination remains difficult.

Light-Activated Drugs Offer a New Approach

A research consortium led by the Institute for Bioengineering of Catalonia (IBEC) has now developed a new class of photoswitchable small-molecule drugs designed to restore important visual functions in animal models of blindness. The findings were published in the Journal of the American Chemical Society (JACS).

The compounds are designed to take over part of the job normally performed by photoreceptors. They can be delivered by injection into the eye, much like other ophthalmic drugs, or even applied as eye drops. Neither method requires genetic modification or an implanted device. The compounds have also shown promising safety profiles, making them potential candidates for future therapies aimed at restoring vision.

“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 at 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 results build on more than 10 years of research. The project included the team led by Pedro de la Villa at the University of Alcalá (UAH), along with researchers 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.

Restoring Visual Function in Blind Animals

The technique relies on photopharmacology, an approach that allows the activity of a drug to be reversibly controlled using light. Researchers alter the chemical structure of a drug by incorporating a light-sensitive molecular switch. When exposed to light, the switch changes the drug’s activity.

Using this strategy, the team created a family of compounds known as prosthe6. These molecules target ON-bipolar neurons and restored saccadic eye movements (optokinetic reflex) in blinded zebrafish larvae, a model commonly used to investigate visual acuity.

The researchers also found that the treatment could restore innate light-avoidance behavior in mouse models of age-related macular degeneration and retinitis pigmentosa.

Healthy mice instinctively prefer darker environments and avoid brightly illuminated spaces. This behavior depends entirely on a functioning visual system. Blind mice lose that preference because they cannot detect the difference between light and dark.

After receiving prosthe6, however, the blind mice once again spontaneously favored dark areas. That behavior indicated that they were able to detect light and use the visual information to guide their actions. No training was necessary.

The effect also occurred at illumination levels similar to those found indoors or outside on an overcast day. This suggests that the treatment restored functional light perception strongly enough to produce natural, visually guided behavior.

Two compounds in particular, prosthe6-12 and prosthe6-15, produced especially promising results. The restored visual behaviors appeared after injection into the eye and also following topical administration as eye drops.

Replacing the Function of Lost Photoreceptors

Prosthe6 works by targeting ON bipolar cells, retinal neurons that normally receive information from the photoreceptors, the cells responsible for sensing light.

“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 retinal circuitry. By doing so, prosthe6 can effectively substitute for some of the function normally provided by missing photoreceptors.

When light reaches the eye, the molecules change shape. That change triggers signaling within the retina in a way that resembles the normal visual process. The researchers describe the compounds as “molecular prostheses” because they allow the retina to respond to light again without implanted hardware or genetic modification.

Another important feature is their ability to function under ordinary illumination. Unlike some optogenetic approaches, they do not require devices that amplify or deliver specialized light. The molecules are small and water-soluble, and they respond to common visible or white light, including normal indoor illumination and daylight, without the need for unusually intense or specialized light sources.

Moving Toward Possible Human Treatments

The findings arrive shortly after publication of the first-ever clinical trial of a photopharmacological drug for vision restoration (which targets an unrelated protein). That milestone suggests that photopharmacology is beginning to move from experimental research toward potential clinical use.

The prosthe6 technology is protected by patent, and researchers are now studying its safety and formulation with the goal of extending how long the restored visual function lasts.

The team is also working with Eyelumina,a spin-off company in formation to secure investments that support translational development and future 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.”

If the approach ultimately proves successful in people, it could provide a widely accessible and affordable alternative to current vision-restoration technologies. It could be particularly important for people with advanced retinal degeneration who currently have no effective treatment options.

The project received early funding from the patients’ foundation Fundaluce (2016), CaixaHealth (Drug4sight, 100010434), the Government of Catalonia (Innovadors, Producte, and Peris programs), and CIBER-BBN (valorization program).

The work also formed part of Rosalba Sortino’s doctoral thesis. The University of Barcelona awarded her the Extraordinary Doctoral Prize for the 2023-24 academic year for the thesis, which she presented at the Faculty of Pharmacy and Food Sciences.

Unlike Webb, which was built to study relatively small regions of the universe in extraordinary depth, Roman is designed to survey vast areas of the sky quickly. Both observatories can detect infrared light, giving astronomers the ability to compare and combine their observations. Used together, the two missions could reveal far more about the universe than either telescope could on its own.

A Hubble-Sized Mirror With a Much Wider View

Roman has a 7.9-foot primary mirror, the same diameter as the Hubble Space Telescope’s, along with two major scientific instruments. Its Coronagraph Instrument will block and filter the light from stars so astronomers can study exoplanets and disks around them. Its Wide Field Instrument is designed to match the sensitivity of Hubble’s cameras while imaging an area 100 times larger.

Over more than 30 years, Hubble has observed roughly 0.1% of the night sky. Roman, by comparison, has the potential to survey the entire sky at the same resolution.

That wide view will allow Roman to find rare objects both close to Earth and across enormous cosmic distances. Scientists expect it to capture dying stars, newly discovered worlds, galaxy clusters and many other targets. University of Arizona researchers will contribute to several major areas of Roman science.

Probing Dark Matter and Dark Energy

One of Roman’s main scientific goals is to investigate dark matter and dark energy, two mysterious components that account for nearly all of the universe. Dark matter exerts gravity but does not give off light, while dark energy is associated with the accelerating expansion of the universe.

NASA selected the U of A’s Arizona Cosmology Lab to support two efforts aimed at better understanding these phenomena, including one wide-field science team and one project infrastructure team.

Elisabeth Krause, a professor of astronomy and physics, leads the wide-field science team “Kinematic Lensing with the Roman Space Telescope.” The group received $2 million to develop a cosmological measurement technique known as kinematic lensing.

By combining Roman images with spectroscopic measurements, the researchers hope to study dark matter and dark energy with greater precision than has previously been possible.

Another U of A group will play a leading role in the multi-institutional project infrastructure team “Maximizing Cosmological Science with the Roman High Latitude Imaging Survey.” Tim Eifler, a professor of astronomy and physics, leads the working group responsible for interpreting Roman’s cosmological observations.

Turning Galaxy Surveys Into a Map of the Universe

Roman will identify galaxies across a wide range of distances, determine where they are located, and measure their characteristics. Astronomers will use those observations to build large catalogs and then apply physical models to determine what those catalogs reveal about the structure and evolution of the universe.

Those calculations will require substantial computing power. The NASA Roman Project awarded Eifler’s lab $800,000 for computing resources that will become part of a new university-wide high-performance computing system scheduled to arrive this fall. The lab will also receive another $2.4 million over five years to carry out the science.

“This infrastructure will take us from catalogs to cosmological interpretation,” Eifler said. “We’ll be able to do things like determine how much dark energy and dark matter are in the universe.”

Eifler also serves as co-chair of the cosmology group, which includes more than 1,000 scientists around the world.

“It’s fantastic to rally the community and to organize us around this science case,” he said. “This really is a dream job.”

Directly Imaging Distant Planets

Roman’s Coronagraphic Instrument will use masks, prisms, detectors, filters, and self-flexing mirrors to demonstrate technologies capable of suppressing starlight. By reducing the overwhelming glare of a host star, astronomers can directly image nearby planets and disks that would otherwise be extremely difficult to see.

Direct imaging represents an important step forward in exoplanet science. Nearly all known exoplanets have been discovered indirectly, including through methods that detect the slight drop in a star’s brightness when a planet passes in front of it.

Roman’s coronagraph will instead help astronomers search for planets by blocking the glare from their stars. The instrument is expected to detect planets that are 100 million times fainter than their host stars, a performance 100 to 1,000 times better than existing space-based coronagraphs.

“It will be a crucial pathfinder for a future Habitable Worlds Observatory,” a recommended telescope that would be specifically designed to search for signs of life in other solar systems, said Schuyler Wolff, an associate research professor of astronomy leading the observation planning working group for the Coronagraph Instrument.

Preparing Roman’s Exoplanet Observations

Lunar and Planetary Laboratory director Mark Marley, associate professor of astronomy Ewan S. Douglas, Steward Observatory assistant research professor Ramya Anche, and astronomy postdoctoral research associate Justin Hom also helped develop the Coronagraph Instrument. They will participate in future science through the observation planning working group.

Marley, together with LPL associate professor Ty Robinson and LPL postdoctoral research associate Zarah Brown, will use Coronagraph Instrument data to study the atmospheres of planets beyond our solar system.

Brown has been modeling the climates and spectra of self-luminous giant planets. These worlds are often young and hot enough to emit their own thermal infrared light.

The model predicts atmospheric temperature, composition and clouds, along with the infrared spectrum each object should produce. Those predictions are especially important because most of these planets have never been observed at these wavelengths.

“That predicted spectrum is critical for planning,” Brown said. “Roman’s coronagraph is working with extremely faint, high-contrast targets, so the team has to schedule enough observing time to detect a candidate without burning more of the mission’s limited time than necessary.”

Anche’s team is examining the structure of extrasolar systems, while Hom is leading efforts to identify the best stars for calibrating the Coronagraph Instrument. Hom also leads precursor observing programs with ground-based telescopes, work that is essential for confirming which targets should be selected for future Roman science programs.

Roman Science Begins in January 2027

Once Roman begins science operations in January, its data will be made available to researchers across the scientific community.

The U of A will lead nine NASA-approved investigations using Roman data, bringing in more than $2 million in funding. Researchers will use those observations to investigate additional topics including supermassive black holes, gravitational lenses, galaxy formation, reionization and cosmic dust.

Researchers analyzed 212 plant-based meat alternatives (PMBAs) and plant-based beverages (PBBs) purchased from UK stores. Every product tested contained at least one of 19 mycotoxins, and some contained several.

The study was led by the University of Parma in Italy and coauthored by Cranfield University. Researchers examined a wide range of products commonly available to UK shoppers, including burgers, vegetarian chicken pieces, vegan sausages, and oat, almond and soy-based milks.

Why Mycotoxins Appear in Plant-Based Foods

Mycotoxins can be especially common in plant-based products because many of their ingredients, including grains, legumes and seeds, may be exposed to mould while they are being grown or stored.

Despite the widespread detection of mycotoxins, the levels measured in the UK products remained below recommended EU guideline levels. The researchers said this reflects the high quality standards maintained by the UK food industry.

Long-Term Exposure Could Still Matter

The concern is not necessarily the amount present in a single product. Previous research studies have indicated that repeated exposure to small amounts of mycotoxins can add up over time and may eventually create health concerns.

Eating individual plant-based products is therefore unlikely to cause problems on its own. However, the researchers say that a diet based entirely on plant foods could increase cumulative exposure to mycotoxins if that exposure is not properly managed. In severe cases, mycotoxin exposure has been associated with liver and kidney damage, suppression of the immune system, and cancer.

The findings provide new data that can be used to estimate dietary exposure and improve risk assessments for consumers in the UK.

Experts Call for Better Monitoring

Andrea Patriarca, Senior Lecturer in Mycology at Cranfield University, said:

“Mycotoxins occur naturally in foods and cannot be completely avoided. As consumers, we should not be frightened or deterred from enjoying a variety of products.

“However, a significant concern arises when new foods enter the market, as there are currently no established regulations to monitor mycotoxins. We collaborate closely with various sectors in the food industry, from farmers to food companies, to help implement effective mycotoxin management integrated within food safety standards. The data from our research helps food safety organisations in assessing risks, particularly in complex multi-ingredient products.

“We are currently collaborating with the University of Parma to evaluate the risks faced by the population based on different dietary habits. Our aim is to advise policymakers and raise awareness among vulnerable consumers.”

The full research paper, “Mycotoxin contamination in plant-based beverages and meat alternatives: A survey of the UK market,” is published in Food Control.

This work was carried out under the Horizon Europe FunShield4Med project (HORIZON-WIDERA-2021-ACCESS-03) Grant Agreement No 101079173 funded by the European Union.