Light-Activated Spinach Nanoparticles Offer Novel Approach to Combat Dry Eye Disease

Scientists have developed LEAF, a spinach-based photosynthetic technology activated by light, which may provide an innovative method for treating dry eye syndrome.

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Plants harness sunlight for photosynthesis, but what if human eyes could achieve similar results?

“Light is essential both for vision and for photosynthesis,” noted David Tai Wei Leong, a biomedical engineer at the National University of Singapore, via email.

In plants, light-driven photosynthesis occurs in thylakoid grana, which generate reduced nicotinamide adenine dinucleotide phosphate (NADPH). This molecule supports antioxidant defenses by neutralizing reactive oxygen species (ROS), a key contributor to dry eye disease (DED). Motivated by this mechanism, Leong and colleagues explored using spinach-derived photosynthetic membranes to generate NADPH for mammalian eye treatment.

As reported in a Cell study, the team created a light-activated nanoparticle system using spinach thylakoids that delivered NADPH to mammalian corneal cells.1 These photosynthetic structures reduced inflammation in corneal cells, offering potential therapeutic value for DED.

Revitalizing Vision Through Light

DED affects 1.5 billion people globally.2 A chronic multifactorial condition, it significantly impairs visual function and reduces quality of life.3 Persistent inflammation and oxidative stress are key disease drivers. Under oxidative conditions, NADPH levels become inadequate to counteract ROS, creating harmful cycles of damage and inflammation.

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Current treatments like cyclosporine A (Restasis) and lifitegrast (Xiidra) face challenges including irritation, side effects, and high costs that limit accessibility. To overcome these barriers, researchers drew inspiration from photosynthetic sea slugs and optimized spinach chloroplasts for nanoparticle delivery.

“Spinach provides consistent chloroplasts in lab protocols, making it a reliable resource,” explained Leong. The team engineered LEAF – containing only thylakoid grana – to function as temporary cellular organelles producing NADPH under ambient light exposure.

Therapeutic Potential of Light-Enhanced Photosynthesis

In DED rodent models, LEAF eye drops significantly improved corneal health upon light exposure. Cellular NADPH supplementation enhanced antioxidant enzyme activity, effectively reducing oxidative stress and inflammation. Human corneal cell studies demonstrated similar anti-inflammatory effects.

“Unlike mammalian cells that may already be compromised by disease, plant photosynthesis operates independently,” noted Leong. “This creates opportunities for therapeutic molecule production beyond diseased cellular capabilities,” he emphasized.

Additionally, LEAF effectively restored NADPH levels and reduced ROS when mixed with DED patient tear fluids. Research fellow Kuoran Xing commented, “The system’s extreme effectiveness requires very low working concentrations, potentially contributing to safety, though ongoing assessments remain necessary.”

University of Tokyo’s Sachihiro Matsunaga praised the approach, calling it “a brilliant step toward vision augmentation through synthetic biology.” While preliminary, this work opens novel pathways for ophthalmic treatments through photosynthetic principles.

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