Spinach and Light Power a Dry Eye Relief Solution

Plants use sunlight for photosynthesis, but what if human eyes could do the same?

“The eye has a very intimate and important interaction with light and for our sight. The plant leaf, too, has the same intimate and important interaction with the same light, but for a totally different reason and outcome,” said David Tai Wei Leong, a biomedical engineer at the National University of Singapore, in an email.

In plants, the light-dependent reactions of photosynthesis occur in stacked, coin-like structures called thylakoid grana, producing reduced nicotinamide adenine dinucleotide phosphate (NADPH), a molecule that powers antioxidant defenses. NADPH helps neutralize reactive oxygen species (ROS), which is a major driver of dry eye disease (DED) in humans. Leong and his team wondered if providing the eye with more NADPH via photosynthesis could help treat DED.

In a recent study published in Cell, Leong and his team developed a light-powered nanoparticle technology built using photosynthetic membranes from spinach that they delivered into mammalian corneal cells.¹ They found that the products of photosynthesis led to a reduction of inflammation in these cells, potentially serving as a therapeutic strategy for DED.

Lighting Up the Eyes

DED is a condition affecting 1.5 billion people worldwide.² It is a multifactorial eye disorder that impairs visual function and substantially diminishes the quality of life for those affected.³ Chronic inflammation and ROS-induced oxidative stress are the major contributors to the disease progression. Under these conditions, the native NADPH in the eyes becomes insufficient to neutralize ROS, leading to a vicious cycle of oxidative damage and inflammation.

Existing pharmaceutical treatments like cyclosporine A (Restasis) and lifitegrast (Xiidra) have notable limitations, including irritation, adverse side effects, and high cost, which limit long-term use and accessibility.

To overcome this limitation, Leong and his team considered sea slugs, which are an exception as animals that can photosynthesize like plants. They steal chloroplasts from algae to survive starvation. Inspired by these unusual traits, the researchers turned to spinach sourced from local supermarkets as a source of chloroplasts. “In plant biology protocols for chloroplast isolation, spinach is the usual source, likely due to its universal accessibility and high chloroplast yield,” said Leong. Using these chloroplasts, he and his team engineered a technology called light-reaction enriched thylakoid NADPH-foundry (LEAF).

This technology acts like a temporary organelle in the animal cells. While regular chloroplasts perform photosynthesis to produce NADPH and adenosine triphosphate (ATP), which cells use to make sugars, LEAF only contains the thylakoid grana of the chloroplasts. These produce NADPH and ATP in ambient light.

Healing Dry Eyes with LEAF

Leong and his team delivered LEAF as eye drops to the DED rodent models, where the corneal epithelial cells rapidly took it up, restoring NADPH levels and corneal tissue integrity upon light exposure. The supplemented NADPH fueled the antioxidant enzymes to scavenge ROS both within and around the cells, reducing oxidative stress and calming the inflammation that drives dry eye disease. Similar anti-inflammatory effects were observed in human corneal epithelial cells.

“Most intriguing was that the plant's photosynthetic NADPH production is undeterred by the dysfunctional state of the mammalian system. In this case, the plant's photosynthetic NADPH production in our system is activated by light. This opens up huge future opportunities where we can produce therapeutic molecules that are independent of the dysfunctional disease cells,” explained Leong.

Additionally, when the researchers mixed LEAF into human tear fluids collected from patients with DED, LEAF restored NADPH levels and significantly reduced ROS. “As the LEAF was quite effective and hence the working concentration is very, very low, this may be part of the reason why the LEAF eyedrop could be quite safe, but further safety assessment is necessary to fully answer this question,” said Kuoran Xing, a research fellow in Leong’s group and a coauthor of the paper, in an email.

Sachihiro Matsunaga, a cell biologist at the University of Tokyo, who also studies photosynthesis in animal cells but was not involved in the study, said in an email, “The idea of transplanting light-dependent reactions into mammalian photoreceptors is a fascinating step toward rethinking how we might augment vision using principles from photosynthesis.” He added, “While this work is still at an early, proof-of-concept stage, it opens up creative possibilities at the interface of synthetic biology and ophthalmology.”