A research team from SAHZU Eye Center, in collaboration with the National University of Singapore, has developed a spinach‑derived nanoscale system that enables mammalian ocular surface cells to perform light‑driven reactions. The approach alleviates oxidative stress and inflammation associated with dry eye disease, as published online in Cell.

Dry eye disease, one of the most common ocular conditions worldwide, affects an estimated 1.5 billion people. Current treatments, including anti‑inflammatory and lubricating eye drops, mainly manage symptoms but do not address the underlying chronic inflammation and reactive oxygen species (ROS) accumulation that drive the condition.

Inspired by photosynthetic sea slugs that incorporate functional chloroplasts from algae, the research team set out to transplant light‑dependent photosynthetic machinery into mammalian corneal cells. After nearly five years of collaborative work, they successfully constructed a nanosystem termed LEAF (Light‑reaction Enriched thylAkoid NADPH Foundry), derived from spinach leaves.

How LEAF Works

LEAF preserves the intact structure and function of thylakoids—the membrane compartments where photosynthesis begins. The researchers removed the NADPH‑consuming dark reaction enzyme system while retaining fully functional thylakoid membranes. Using an innovative nano‑encapsulation technique, they coated the thylakoids with a biocompatible material, producing particles approximately 400 nanometers in diameter that can be efficiently taken up by mammalian cells.

Formulated as eye drops, LEAF is delivered to corneal cells. Upon exposure to ambient visible light, it initiates a complete photosynthetic light‑reaction chain, autonomously generating NADPH and ATP. The system can operate repeatedly across light‑dark cycles, functioning like a light‑switchable bio‑battery.

Breaking the Vicious Cycle

Dry eye disease creates a self‑perpetuating cycle of chronic inflammation and oxidative stress. Excess ROS trigger inflammation, which in turn generates more ROS, leading to persistent cell damage.

LEAF intervenes at the source. Inside cells, it produces NADPH to restore antioxidant capacity and reverse inflammatory status. Outside cells, antioxidant enzymes carried on the LEAF surface are activated by NADPH, directly scavenging ROS in the tear microenvironment before inflammation spreads.

Compelling Preclinical Data

In a mouse model of dry eye, a single topical dose of LEAF under normal ambient light significantly elevated corneal NADPH levels within 30 minutes. After five days, corneal damage scores dropped substantially, and tear secretion increased to near‑healthy levels.

In tests using tears from human dry eye patients, 30 minutes of light exposure increased NADPH levels approximately 20‑fold while reducing harmful ROS by over 95%.

Safety assessments showed no adverse effects in guinea pig skin sensitization tests or rabbit eye irritation studies. Long‑term administration did not alter intraocular pressure or produce systemic toxicity.

Looking Forward

"Our study demonstrates that mammalian tissues can acquire photosynthetic capability and exert beneficial effects under inflammatory conditions," said Prof. Ye Juan, corresponding author of the paper. "LEAF is prepared from supermarket spinach, has a strong biosafety profile, and works under ambient light without requiring additional light sources. Patients receive therapeutic benefits simply by using their eyes normally."

The research team is now advancing the technology toward clinical translation and exploring broader applications for other ocular surface diseases.