A new study conducted by researchers in the US has found that a new drug that can be delivered directly into the eye via an eye dropper can shrink down and, in some cases, even dissolve cataracts. Cataracts are the leading cause of blindness affecting tens of millions of people. To date the only way to treat them is painful and often expensive surgery. The eye drops have yet to be tested on humans, but this is to be the next stage of the study.
Jonathan King, a molecular biologist at Massachusetts Institute of Technology in Cambridge not affiliated with the study said that “This is a really comprehensive and compelling paper—the strongest I’ve seen of its kind in a decade”. King has been investigating cataract proteins since 2000.
The major component of the fiber cells that form the eyes’ lenses are crystallins. Unfortunately, the unique properties of these cells mean that they are prone and susceptible to damage, explains Jason Gestwicki associate professor of pharmaceutical chemistry at UCSF.
“Shortly after you’re born, all the fiber cells in the eye lose the ability to make new proteins, or to discard old proteins,” said Gestwicki, “So the crystallins you have in your eye as an adult are the same as those you’re born with.”
These crystallins must maintain the flexibility and transparency of fiber cells if our lenses are to function properly. Proteins known as chaperones keep the crystallins soluble.
Keeping the crystallins healthy is tricky as clumped-together pathological configurations of crystallins are more stable than healthy forms of crystallins. Thus the fiber-cell chaperones need to resist the tendency of crystallins to clump. The clumped-together proteins are called amyloids. These amyloids make it harder for light to pass through the lens creating the cloudiness cataract is known for.
Scientists do not know exactly what causes cataracts but the majority of cases are age related. The US National Eye Institute reports more than half of all American have a cataract or have had cataract surgery by the age of 80. https://nei.nih.gov/health/cataract/cataract_facts
A study that conducted surveys in 39 countries found that globally the number of people who are visually impaired is estimated to be 285 million. Of this figure 39 million are blind (with uncertainties of 10-20%). 33% of the cases of visual impairment were caused by cataracts, while cataracts were the first cause of blindness; making up 51% of all blindness cases. The study indicates that visual impairment, in particular cataracts, is a major health concern.
Most of the people who suffer from blindness live in developing countries. Over half of these people are blind as a result of cataracts. Given that the money and facilities needed to perform a surgical procedure to remove a cataract is not available in many developing countries, having an eye drop as an alternative to surgery could make a tremendous difference.
The new eye drops are based on a naturally-occurring steroid called lanosterol. Researches decided to explore the possibility of using lanosterol as a treatment for cataracts after hearing of two children in China who had inherited a congenital form of cataract. The children’s parents had not suffered from cataracts. The children both had a mutation that prevented the production of lanosterol. The parents did not have this mutation.
As the children did not produce lanosterol and got cataracts and the parents were producing lanasterol and did not get cataracts it was thought, by scientists, that the lanosterol could stop the defective crystalline proteins from clumping together and forming cataracts (in the non-congenital cases).
Lanosterol-based eye drops were used in three types of experiments. Firstly, the scientists worked with human lens in the Laboratory. Secondly they tested the effects on rabbits and finally they tested the eye drops on dogs with naturally occurring cataracts. The results were as following. In the experiment with human lens there was a decrease in cataract size. After six days all but two of the 13 rabbits had experienced a decrees in the severity of their cataracts. Likewise, the cataracts of the dog shrunk almost disappearing. The results were published in Nature.
The study identifies lanosterol as a key molecule in the prevention of amyloids and points to a new way to approach cataract prevention and treatment. The next step is for the researchers to further investigate how the lanostero-based eye drops are working and then to see if they get the same positive results when the drops are tested on humans.
Featured photo credit: Doing Mercy via doingmercy.com
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