Spinach-derived nanoparticles outperform cyclosporine A in preclinical dry eye models

A research team at the National University of Singapore (NUS) has developed a plant-derived nanotechnology that enables corneal cells to produce a key antioxidant molecule when exposed to ambient light, with preclinical studies suggesting the approach may reverse corneal damage associated with dry eye disease within 5 days. The findings, published May 15, 2026, in Cell, represent a novel mechanistic departure from current pharmacologic approaches to dry eye management.¹

"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," said Dr Xing Kuoran, first author of the study.

Trial and research overview

The NUS team, led by Associate Professor David Leong Tai Wei from the Department of Chemical and Biomolecular Engineering, engineered a nanosized construct designated LEAF — an acronym for Light-reaction Enriched thylAkoid NADPH-Foundry. LEAF consists of structurally preserved thylakoid grana isolated from spinach leaves via a patented mechanical and chemical extraction process. The resulting particles measure approximately 400 nanometres in diameter.

The construct was designed to function as a dedicated factory for nicotinamide adenine dinucleotide phosphate (reduced form) — NADPH — a molecule central to the cornea's antioxidant defences. By retaining only the light-harvesting thylakoid components while removing the portion of the chloroplast that consumes NADPH, the team reported that LEAF produces approximately 20% more NADPH than unpackaged thylakoids.

In laboratory studies using inflamed corneal cells, LEAF restored NADPH levels within 30 minutes of light exposure, suppressed reactive oxygen species (ROS), and shifted corneal immune cells from a pro-inflammatory to an anti-inflammatory phenotype. When applied directly to tear samples from patients with dry eye disease, LEAF increased NADPH levels approximately 20-fold and reduced hydrogen peroxide — a principal oxidative stressor — by more than 95%, according to the researchers.

Two preclinical animal trials were conducted in collaboration with ophthalmologists at the Eye Centre of the Second Affiliated Hospital, Zhejiang University. LEAF administered as eye drops under ambient indoor lighting reversed corneal damage to near-healthy levels within five days and outperformed cyclosporine A (Restasis) in the first preclinical trial. Safety assessments conducted over 2 months, including skin sensitisation, eye irritation, and organ toxicity studies, revealed no adverse effects. Human clinical trials have not yet been initiated.

Clinical context

Dry eye disease — formally termed keratoconjunctivitis sicca — affects an estimated 1.5 billion people worldwide and carries substantial clinical and economic consequences, including corneal scarring, chronic pain, photophobia, and blurred vision.² The annual economic burden in the United States alone has been estimated at approximately US$3.84 billion, according to the researchers. The condition has also been associated with depression, anxiety, and reduced workplace productivity.²

At the cellular level, disease progression is driven by an oxidative cycle in which corneal inflammation generates ROS that overwhelm endogenous antioxidant systems — primarily NADPH-dependent pathways — creating a self-amplifying cycle of cellular injury. Current approved therapies, including cyclosporine A (Restasis) and lifitegrast (Xiidra), address inflammation through targeted immunomodulatory mechanisms but are associated with high treatment costs and adverse effects that can limit long-term adherence.³

Drug and technology background

LEAF is not a conventional pharmaceutical agent. It is a biologically derived nanoparticle that functions by introducing functional photosynthetic machinery into mammalian cells. The mechanism is conceptually analogous to the behaviour of sacoglossan sea slugs, which incorporate algal chloroplasts into intestinal cells and sustain limited photosynthetic activity when food-deprived — the only documented instance of photosynthesis occurring within animal tissue.

The NUS team identified the eye as a suitable target organ because of its direct exposure to visible light, a prerequisite for the light-driven NADPH production that LEAF is designed to facilitate. Delivered as eye drops at doses described as low enough to avoid interference with colour perception, LEAF operates through two proposed pathways — intracellular and extracellular NADPH restoration.

Expert and interpretive framing

The study is notable for its mechanistic originality, representing a first-in-class demonstration of transplanted plant photosynthetic machinery producing biologically active molecules in mammalian tissue. The researchers also propose broader applications in oxidative stress-related conditions affecting light-accessible tissues such as the retina and skin.

However, the findings remain at a preclinical stage, and significant translational questions persist. The immunogenicity of plant-derived organelle components in human ocular tissue has not been characterised in clinical populations. Comparisons with Restasis were made in animal models rather than controlled human trials, and extrapolation to clinical efficacy should be approached with caution.

Limitations and next steps

The primary limitation is that all efficacy and safety data are derived from laboratory and animal studies. No human clinical trial data are available, and no regulatory submissions have been filed. The animal models used, the sample sizes, and species-specific variables were not detailed in the press release. Direct comparative data against lifitegrast or other standard-of-care agents were not reported. The team has indicated plans to conduct clinical trials but has not disclosed timelines or study designs.

References:

1. Xing K, Leong DTW, et al. Light-reaction enriched thylakoid NADPH-foundry for dry eye disease. Cell. Published online May 15, 2026. https://www.cell.com/cell/fulltext/S0092-8674%2826%2900469-1

2. Craig JP, Nichols KK, Akpek EK, et al. TFOS DEWS II definition and classification report. Ocul Surf. 2017;15(3):276-283. https://doi.org/10.1016/j.jtos.2017.05.008

3. Sheppard JD, Donnenfeld ED, Holland EJ, et al. Effect of loteprednol etabonate 0.5% on initiation of dry eye treatment with cyclosporine 0.05%. Eye Contact Lens. 2014;40(5):289-296. https://doi.org/10.1097/ICL.0000000000000050

4. Tsubota K, Pflugfelder SC, Liu Z, et al. Defining dry eye from a clinical perspective. Int J Mol Sci. 2020;21(23):9271. https://doi.org/10.3390/ijms21239271