The unassuming vial of eye drops could easily belong on a pharmacy shelf. But swirling inside are microscopic bits of photosynthetic machinery made from plants. Within minutes of giving the drops to mice, their eyes gain an extraordinary ability beyond that of any mammal. Like a leaf, they can now harness the power of sunlight.
Photosynthetic eyes sound like they’re straight out of science fiction, but there’s a practical use researchers are after. Chemical reactions during photosynthesis generate powerful antioxidants that ward off inflammation and could potentially treat a range of health conditions.
Called LEAF, the technology is creative, effective, and simple. Its main ingredient can be found in grocery store spinach. In a paper detailing the work, researchers at the National University of Singapore and collaborators say they developed a gentle chemical cocktail to extract some of the core mechanisms used in photosynthesis.
Introduced to mammalian cells—including those that make up the cornea and immune cells—the floating photosynthetic particles made themselves at home and restarted work as usual when exposed to light. In mice with dry eye disease, LEAF continuously pumped out protective antioxidants, healed corneal scarring, and kept their eyes hydrated for days.
The animals scurried around as usual, without any inkling their eyes were now part plant.
“This is an exciting finding as we have, for the first time, demonstrated that plant photosynthetic machinery can be transplanted into mammalian tissue to generate biologically useful molecules, powered entirely by the same light that enables our vision,” study author Kuoran Xing at the National University of Singapore said in a press release. “We, too, can have limited photosynthetic abilities.”
Planting an Idea
Dry eye disease is one the most common eye problems, affecting roughly 1.5 billion people worldwide. Symptoms are hardly trivial. Irritation and chronic pain make daily life miserable. Overtime, the disease causes scarring of the cornea, blurred vision, and sensitivity to light. The condition has been linked to depression, anxiety, and other health struggles.
Current treatments address the underlying inflammation, but they’re expensive, have limited availability, and long-term use can provoke uncomfortable side effects throughout the body.
At the heart of the disease is a vicious, runaway cycle of cellular dysfunction. When our cells generate energy, they also produce byproducts called reactive oxygen species. Like tiny bullets, these wreak havoc if left unchecked. Some tunnel through delicate protective membranes and disrupt protein function. Others damage DNA, and in severe cases, cause cell death.
Our bodies constantly mop them up with a molecule called NADPH. But during inflammation the defenses are overwhelmed. Reactive oxygen species destroy the cells’ ability to make NADPH. Left unchecked, the cell enters a death spiral: It tries to maintain its supply of energy, but this ironically, generates more bullets and these activate immune cells. Trying to boost NADPH under these conditions is a losing battle.
That’s why spinach caught the team’s attention. Plants make NADPH during photosynthesis. Powered by sunlight, they churn out energy and the antioxidant in completely different ways than our cells. Theoretically, adding plant-based machinery into our cells could bypass existing cellular mayhem and provide a new source of NADPH.
A plant-animal crossover sounds preposterous, but it already occurs in nature. The sacoglossan sea slug eats microalgae high in chloroplasts—the photosynthetic organelle in plant cells—and stores them intact in its guts. When it can’t find food, the slug can survive on photosynthesis.
In previous studies inspired by the slug, scientists have tried transplanting core bits of photosynthetic machinery called thylakoids into animal cells. They look like stacks of coins, but their interior structure is far more complex—any misalignment results in catastrophic failure.
Researchers had already tried transplanting bits of this machinery into mouse knee cells but found it required high levels of an additional chemical to keep it in working order. In another study, a team targeted rheumatoid arthritis, an inflammatory disease of the joints. But getting light into the tissues was a struggle, and the system needed lengthy exposure.
Eyes, however, are a natural window to visible light.
Eyes on the Prize
In the new study, the team’s main invention was figuring out how to keep thylakoids intact while stripping away other parts of the chloroplast that destroy NADPH.
They eventually learned how to extract thylakoid particles from spinach in such a way as to maximize NADPH production. Measuring roughly 400 nanometers across—the size of a very small bacteria—the particles produce NADPH when exposed to ambient light.
The team tested them on two types of cells responsible for dry eye disease: Large immune cells called macrophages and corneal cells. In petri dishes, both cell types readily soaked up LEAF. Once released inside the cell, the plant thylakoids steadily pumped out NADPH.
Within 30 minutes of light exposure, the amount of reactive oxygen species tanked. Angry macrophages relaxed into a state that battles inflammation. In tears collected from patients with dry eye disease, LEAF boosted NADPH levels roughly 20-fold and slashed a damaging oxidative chemical over 95 percent. Tests examining the wider metabolic landscape showed cells reverted to a healthier state after being treated with LEAF.
This photosynthesized NADPH supply can “power antioxidant metabolism,” promote cell repair, restore balance, and break the vicious cycle, wrote the team.
In a final test, they treated a mouse model of dry eye disease with the drops twice daily for five days and pitted it against an approved chemical treatment. LEAF easily entered the animal’s eyes after 30 minutes. Under ambient light, the system doubled the amount of NADPH and reversed corneal damage, outperforming the therapeutic drug.
Surprisingly, although the treatment is made of plant matter, it didn’t trigger immune attacks in the eyes or other parts of the body, such as the liver or heart. But the team didn’t specifically test to see if the drops improved the animals’ eyesight or if adding the photosynthetic machinery changed their perception.
That said, LEAF is especially well-suited for clinical use. It’s easily manufactured and stored and was consistently effective across four independent batches made in Singapore and China, with each sourced from local spinach. The nanoparticles are stable for two weeks at room temperature and last up to a year at -80 degrees Celsius.
Because LEAF “is derived from spinach, delivered as a simple eye drop, [and it] requires no external device or power source…we believe it has a strong potential for clinical translation,” said study author David Tai Leong.
Beyond dry eye disease, LEAF could be made into a cream that harnesses sunlight to treat skin inflammation disorders. The team is also looking to generate photosynthetic molecules in deeper organs and boost the health of mitochondria, the cell’s energy factories.
“It is almost surreal when thinking of a possible future reality where human cells can have some limited but beneficial form of photosynthetic ability not only in the eye but elsewhere, too,” said Leong.
