An international team of scientists led by Anglia Ruskin University (ARU) has announced "extremely positive results" from laboratory trials of a compound that could one day offer a non-operative option for cataract treatment, currently curable only by surgical replacement of the lens.
They described their study, published in Investigative Ophthalmology and Visual Science, as "a significant step forward towards treating this extremely common condition with drugs rather than surgery".
The new study builds on the team's previous animal research showing that lens optics develop much earlier in gestation than was previously believed. They had then uncovered the role of a protein called aquaporin, also known as membrane intrinsic protein and responsible for water passage in the lens, in the disrupted optical development that leads to cataract formation. Studies in mice suggested that aquaporin regulates both the mechanical and optical functions of the lens, as stiffness of the lens correlates directly with amounts of the protein.
The team explained that disorganisation of crystallins and aquaporin in the lens causes clumps of protein to form that scatter light, making the lens lose transparency and severely reducing transmission to the retina. This 'clouding' of the lens affects the quality of vision and over time causes the visual loss sometimes amounting to blindness that affect millions of people worldwide who succumb to cataracts. Understanding the mechanism opened the way to developing treatments to correct it.
Refractive Improvements in Mice
For their latest research, the team carried out advanced optical tests in a mouse model to show how cataract-linked mutations affect the gradient refractive index – a key optical parameter that is needed to maintain high focusing capacity – and promote lens opacification. They confirmed that α-crystallin mutations alter the refractive index gradient of mouse lenses in distinct ways.
They then tested the effect on the optics of the lens of treatment with an oxysterol compound that had been proposed as an anti-cataract drug. The oxysterol, called VP1-001, was applied topically to one eye in 26 mice, while the drug vehicle only (8% cyclodextrin) was applied in the other. Each was administered as a single drop onto the ocular surface, three times per week for two weeks for a total of seven treatments. Nine untreated mice served as a control group. Slit lamp biomicroscopy was used to analyse the lens in live animals and to provide apparent cataract grades.
Results showed that treatment with VP1-001 produced an improvement in refractive index profiles in 61% of the treated lenses, but not in the untreated eyes of the same animals or in controls. This showed that the protein organisation of the lens was being restored by oxysterol, they said, resulting in the lens being better able to focus. They also showed a reduction in lens opacity in 46% of cases after oxysterol treatment.
'First Research of This Kind'
Team leader Prof Barbara Pierscionek, deputy dean for research and innovation in the Faculty of Health, Education, Medicine and Social Care at ARU, said: "This study has shown the positive effects of a compound that had been proposed as an anti-cataract drug but never before tested on the optics of the lens. It is the first research of this kind in the world.
"It has shown that there is a remarkable difference and improvement in optics between eyes with the same type of cataract that were treated with the compound compared with those that were not."
However, she noted: "Improvements occurred in some types of cataract but not in all, indicating that this may be a treatment for specific cataracts. This suggests distinctions may need to be made between cataract types when developing anti-cataract medications."
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