With around 20 million people globally suffering blindness caused by cataracts, it is the leading reason for sight loss. And with cataracts also developing to some extent in over half of people aged above 65, they also partially impair the sight of tens of millions more.
Despite the large numbers of people affected, there are no readily-used drug treatments available. This highlights the importance of recent work at New York University Abu Dhabi to characterise an anti-cataract chemical produced by a locally found plant.
As part of her course, Yumi Gambrill, a recent graduate of the university, spent about a year working to identify a chemical with anti-cataract properties found in a plant called Cleome rupicola. The hope is that, eventually, the substance could be used in drugs as a relatively low-cost cataract treatment.
Although cataracts can be successfully removed – an artificial lens replaces the original cloudy one – not everyone has access to surgery.
“Cataracts tend to disproportionately affect people in developing countries, where people are less likely to be able to access or afford cataract surgery, or there are heightened complications,” said Ms Gambrill.
“There’s a pretty strong push to find a cataract [drug] treatment. Much of drug discovery in general is based off what we know of plants.”
It was not by chance that C. rupicola was identified as having anti-cataract properties: ethnographic literature and old-style healers indicate that the plant was used by traditional communities in the UAE to treat cataracts.
“I wanted local relevance. There’s a long history of Islamic medicine – incredibly advanced knowledge that ties into medicine in general and UAE culture,” said Ms Gambrill, a 22-year-old American who majored in chemistry with a minor in political science.
“It’s an opportunity to bring together history and modern technology.”
In spring last year, Ms Gambrill went to the Masafi area in north east UAE, around the border between Fujairah and Ras Al Khaimah.
With the help of an expert from the International Center for Biosaline Agriculture in Dubai, she identified C. rupicola in the rocky countryside and collected samples, probably several hundred grams in total, which were then freeze-dried.
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Several months of purification in the laboratory of Professor Pance Naumov, where Ms Gambrill carried out her project with the help of postdoctoral researchers Dr Patrick Commins and Dr Stefan Schramm, yielded 0.8 milligrams of a compound from the plant’s fruits.
An early step in the laboratory analysis was to see if this substance contained antioxidants, which help to protect against some of the changes in the lens that cause cataracts.
There is more than one biochemical pathway that can cause cataract formation, but cataracts that form because of ageing are especially associated with the presence in cells of reactive oxygen species, or ROS, which are forms of oxygen with a free electron or negatively charged particle. As people get older, it becomes harder for lens cells to deal with the damage ROS cause, and that includes changes to the shape of lens proteins that make the lens turn white.
It was found that the compound did, indeed, have antioxidant properties.
As well as looking for antioxidants, several other chemical analysis techniques were used.
Mass spectroscopy (which analyses substances based on their mass and charge) determined the molecular mass of the compound, while nuclear magnetic resonance spectroscopy, a technique that looks at magnetic fields around atomic nuclei, gave clues about its structure.
“Signals from NMR are like fingerprints from a compound. It’s really useful when you’re trying to match up a known compound with an unknown,” said Ms Gambrill.
The chemical contains six carbon atoms, 11 hydrogen atoms and one atom each of nitrogen, oxygen and sulphur.
From the various types of tests, the Ms Gambrill and her co-researchers came up with two candidate structures containing the right mix of atoms. These were synthesised in the laboratory and analysed.
Neither compound matched with any already-known chemicals, something that would have made identification easier.
“These two candidates are the two different structures that we thought our compound could be. They’re novel compounds, which means they’ve never been studied before,” said Ms Gambrill.
“One of the easiest things is to compare your data from your unknown compound to a library of known [substances]. But we weren’t getting any hits – there was no data.”
However, one compound produces results very similar to those of the chemical from C. rupicola. Further work by Dr Commins will try to crystallize the compound, as this will permit additional tests.
The eventual aim is to publish a scientific paper of the findings, with the hope being that the substance could be used in an anti-cataract drug. Ms Gambrill said it would be "incredible" if the C. rupicola chemical was eventually used clinically, especially as there have been "plenty of unsuccessful attempts" to identify something usable against cataracts.
“This would be a huge advance for cataract research [with] massive implications, especially for patients that cannot afford the [surgical] treatment,” she said.
“When you do research with the potential of finding something incredibly useful, that’s a huge motivating factor. That’s the reason that helps me get through the days when things don’t go right.”
But why has no widely used anti-cataract drug been developed up to now? Part of the reason, suggested Dr Julie Sanderson, a senior lecturer in the School of Pharmacy at the University of East Anglia in the United Kingdom who has worked on and off on cataract-related work for three decades, is that cataract surgery is simple and usually successful, so drug companies have had less incentive to put money into research. Also, the nature of the condition means that clinical trials would be long and expensive.
Nevertheless, she said, if a substance was found to be effective at combating cataracts, “that would be good, if there was the money to follow up”.
In scientific literature there have been, she said, "plenty of papers" describing substances of potential use against cataracts. But, given that it was used in traditional medicine in the Gulf, the chemical in C. rupicola could perhaps be the one that breaks through and is eventually used against cataracts.
