Researchers at the National University of Singapore (NUS) are pioneering a treatment for dry eye disease (DED) that draws inspiration from how plants harness sunlight. Their approach uses a light-activated technology derived from the photosynthetic membranes of the spinach plant, which enables the eye to stay continuously hydrated, according to a press release that highlights the new study published in Cell.
A team led by Associate Professor David Leong Tai Wei from the Department of Chemical and Biomolecular Engineering in the College of Design and Engineering at NUS developed a fundamentally different approach by transplanting functional plant-derived photosynthetic machinery into corneal cells, enabling them to harvest ambient light and produce nicotinamide adenine dinucleotide phosphate (NADPH) independently from the cells' own NADPH production pathways. The technology is delivered as simple eye drops at doses so low that it does not interfere with color perception. In preclinical studies, it reversed corneal damage to near-healthy levels within 5 days, according to the press release. A second preclinical trial, also in collaboration with ophthalmologists from Eye Centre of Second Affiliated Hospital, Zhejiang University, confirmed the therapeutic effect. Safety assessments, including skin sensitization, eye irritation, and organ toxicity studies conducted over 2 months showed no adverse effects.
The NUS researchers chose the eye because it is one of the few organs in the human body that absorbs visible light—just like plant leaves. They engineered LEAF (Light-reaction Enriched thylAkoid NADPH-Foundry), which is a nanosized, structurally preserved version of the thylakoid grana—the tightly stacked membrane compartments inside the chloroplasts of plant cells where light energy is harnessed and converted to NADPH molecules. During photosynthesis, the NADPH molecules are subsequently used to produce glucose, which provides energy and food for the plant.
According to the press release, the team's core innovation was to strip away the part of the chloroplasts that consumes NADPH while keeping the thylakoids, where the light-reaction machinery of photosynthesis is, intact. The resulting nanosized package acts as a dedicated NADPH factory that is capable of producing about 20% more NADPH compared to unpackaged thylakoids.
Prepared from the familiar spinach leaves using a patented, mild mechanical and chemical extraction method developed by the NUS team, the particles are roughly 400 nanometres across—small enough to be readily absorbed by cells. LEAF, when in the cells, then produces photosynthetic NADPH upon exposure to ambient light sources, which tackles DED via 2 pathways inside and outside the cell.
In laboratory tests on inflamed cells, LEAF restored NADPH levels within 30 minutes of light exposure, suppressed ROS, and pivoted immune cells in the cornea from a pro-inflammatory to an anti-inflammatory state. When tested directly in tear samples collected from patients with DED, LEAF increased NADPH levels roughly 20-fold and reduced hydrogen peroxide, a key cell-damaging oxidant, by more than 95%. The team plans to conduct clinical trials to further validate the technology.
Because oxidative stress underpins a wide range of inflammatory conditions beyond DED, the team also sees potential for LEAF-based approaches wherever the body's antioxidant defenses are overwhelmed, particularly in tissues that are naturally accessible to visible light such as the retina, skin, and underlying skeletal muscles. They are also developing new strategies that can produce therapeutically useful photosynthesized molecules in internal organs without the need for visible light penetration, the press release stated. OM