Cataracts are cloudy regions that develop in the lens of the eye. They take years to form, but can be dissolved in a matter of weeks with a substance called lanosterol, a precursor to cholesterol and several related sterols.
The Nature paper showed that an injection followed by eye drops containing lanosterol reversed clouding in the lenses of dogs after treating them for just six weeks. Veterinarians may soon be able to substitute eye drops for the scalpel to treat their canine patients, which is just as well as cataracts are common in some pedigree dogs including, ironically, guide dogs for the blind.
The Science paper reports the discovery of a class of small molecules also derived from cholesterol. These sterols were shown to reverse lens clouding in mice and, remarkably, the effects were seen in just two weeks.
Cataracts and the clouding that happens as a result of protein aggregation was considered a point of no return. Until these two new studies came along, no one even thought that restoring the transparency of the lens was an alternative. These papers change that perspective and open a completely new therapeutic strategy to treat cataracts in the future.
Cataracts occur as a result of protein clumping together on the eye’s lens, preventing light from reaching the retina. Once the cataract is formed, there is one option: surgery. Cataract surgery involves removing the natural lens through tiny incisions and replacing it with a plastic “intraocular” lens.
Cataract surgery is one of the most commonly performed procedures and it has a high success rate. The problem is that there simply aren’t enough ophthalmic surgeons to perform all of the procedures that are needed.
In 2010, there were 95m people requiring cataract surgery, worldwide, and of these people 20m were blind as a result. With people living longer, the problem is only going to get worse.
If you live long enough, you will develop cataracts. So something that radically shifts not only our understanding of cataracts but also its treatment is badly needed. And the two recent studies may be just that something. They herald the most remarkable discovery to emerge in the field of cataract therapies since Harold Ridley developed the intraocular lens in the mid-20th century.
It’s not just cataracts
The Science paper shows that selected sterols could help in the treatment of a host of other human diseases such as cardiomyopathy and neurodegenerative diseases where similar proteins are involved. As more details on the mechanism of action become known, it is possible that such sterol-based drugs could have applications for the treatment of Parkinson’s disease, Alzheimer’s disease and other types of dementia.
Another possible application for sterol-based treatments is presbyopia (long-sightedness). This is the other universally experienced ageing effect on the eye lens. When we reach middle age, our arms need to grow a couple inches every year so we can continue to type and read the computer screen. It is believed that presbyopia is the first stage in age-related cataracts. By mid-life, the lens proteins have accumulated significant damage, enough to change their properties and start the process of forming “aggregates” that eventually become a cataract. So the research described in the two papers really does offer something momentous: the preservation of our sight as we age.