NUS study finds photosynthesis could treat dry eye disease
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In pre-clinical studies, the novel eye drops created by the team outperformed Restasis, an existing treatment for dry eye disease.
PHOTO: COLLEGE OF DESIGN AND ENGINEERING, NUS
- NUS researchers are using plant photosynthesis to treat dry eye disease, a common condition caused by inflammation and reactive oxygen species.
- They developed "LEAF" particles from spinach which generate NADPH from ambient light, suppressing reactive oxygen species in affected corneal cells.
- Lab and animal tests showed LEAF eye drops reversed corneal damage; this technology has strong potential for wider clinical translation in human cells.
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SINGAPORE - In plants, the process of photosynthesis converts light energy into chemical energy in the form of sugars.
National University of Singapore (NUS) researchers are now tapping the process to treat dry eye disease.
Also known as keratoconjunctivitis sicca, dry eye disease is a common eye condition that affects more than 1.5 billion people worldwide. It can cause corneal scarring, chronic pain and sensitivity to light, with studies also linking the condition to depression and anxiety.
The disease is caused when inflammation in the corneal region generates reactive oxygen species (ROS), molecules that can damage cells.
This is neutralised in healthy eyes via the production of antioxidants, driven by nicotinamide adenine dinucleotide phosphate (NADPH) – a naturally occurring chemical compound.
In inflamed eyes of those with dry eye disease, however, ROS levels overwhelm the cornea’s natural defences, resulting in the generation of even more of such aggressive molecules.
Current treatments such as cyclosporine A and lifitegrast – marketed as Restasis and Xiidra, respectively – target such inflammation, but their long-term use is limited by high costs and adverse side effects such as temporary eye irritation or burning.
In plant cells, light energy is harnessed and converted into NADPH molecules, which are utilised in photosynthesis to produce glucose, thereby supplying energy and food for the plants.
There are some examples of animals harnessing photosynthesis. The sacoglossan sea slug stores chloroplasts – the organelles, or small structures within cells, responsible for photosynthesis – from microalgae within its intestinal cells. These sea slugs can live off nutrients made via photosynthesis when starved.
Now, a team of researchers – led by Associate Professor David Leong from the chemical and biomolecular engineering department at NUS’ College of Design and Engineering – have transplanted this process from plants into corneal cells, allowing them to harvest ambient light and independently produce NADPH.
Associate Professor David Leong (centre) and his team from the National University of Singapore extracted and transplanted the plant machinery responsible for photosynthesis into the eye’s corneal cells via eye drops to treat dry eye disease.
PHOTO: COLLEGE OF DESIGN AND ENGINEERING, NUS
The researchers observed that the eye, much like plant leaves, absorbs visible light.
They developed nano-sized versions of the thylakoid grana, the membrane compartments within the chloroplasts of plant cells. This process involves stripping away the part of the organelles which consumes NADPH while keeping the thylakoids, which are responsible for the light-dependent reactions of photosynthesis.
Extracted from spinach leaves using a patented method developed by the NUS team, these particles are dubbed light-reaction enriched thylakoid NADPH-foundry (LEAF).
Just 400 nanometres in size, the particles are small enough to be readily absorbed by cells.
Once absorbed, LEAF produces NADPH upon exposure to ambient light sources, which tackles dry eye disease, both within and outside the cell.
Lab tests on inflamed cells showed that within half an hour of light exposure, LEAF was able to suppress ROS, restore NADPH levels and restore the cornea’s immune cells to an anti-inflammatory state.
Tested in tear samples from 20 dry eye disease patients at Zhejiang University Eye Hospital in China, LEAF was shown to increase NADPH levels twentyfold and reduce hydrogen peroxide, which damages cells, by more than 95 per cent.
In tests on rodents, the particles – administered as eye drops under ambient indoor lighting – were shown to reverse corneal damage to near-healthy levels within five days, outperforming existing treatments.
The team’s findings were published in the scientific journal Cell on May 15.
“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 NUS’ Dr Xing Kuoran, who is the study’s first author.
Prof Leong said the technology has a “strong potential for clinical translation”.
He suggested that LEAF could be employed in other parts of the body, such as the retina, skin and underlying skeletal muscles.
The team is also exploring the production of therapeutically useful photosynthesised molecules in internal organs, without the need for visible light penetration.
“It is almost surreal when thinking of a possible future reality where human cells can have some limited but beneficial form of photosynthetic ability not only in the eye, but elsewhere, too,” said Prof Leong.
