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Eyedrops hold potential for cataracts

Dropping lanosterol into eyes could treat, prevent the common disease

The Columbian
Published: July 26, 2015, 5:00pm

In coming decades, doctors might be able to treat or prevent cataracts with eyedrops — all because of an unexpected discovery, revealed during a genetics study, about a molecule that helps make cholesterol in human cells.

Lanosterol, as the substance is known, can reverse the accumulation of proteins in the lens of the eye that appear to cause cataracts, Dr. Kang Zhang and his colleagues at the University of California, San Diego discovered.

The results of the team’s work were published Wednesday in the journal Nature, and may hold promise for the tens of millions of people around the world who suffer from cataracts. Currently, the disease is treatable only through surgical removal of the lens. But potentially, thanks to the lanosterol discovery, patients might someday be able to prevent or treat the disease by using eyedrops or getting an injection — avoiding the risks, discomfort and costs of surgery and recovery.

“It would have a huge public health impact,” said Dr. Robert B. Bhisitkul, a professor of ophthalmology at the UC San Francisco School of Medicine who was not involved in the research. “Preventing or reversing cataracts with an eyedrop has been the Holy Grail in ophthalmology since the field began.”

Zhang, who is well-known for his research on retinal diseases, had no idea that he’d be investigating lanosterol as part of the study.

“It was a surprise,” he said.

The work began as an investigation of the genetics in a single family in which two parents without cataracts, who happened to be first cousins, had four children: three with cataracts and one without.

Sequencing and analyzing the genomes of the parents and the children, Zhang and his team were able to zero in on a likely cause of the diseased kids’ cataracts — each had two copies of a mutated version of a gene called LSS, which was known to be involved in the production of lanosterol. (The researchers later found a second family with cataracts that also had a mutation in the LSS gene.)

To see if a problem producing lanosterol was involved in causing cataracts somehow, the researchers conducted tests, introducing various types of cataractlike crystalline protein mutations into human lens cells in lab dishes and seeing whether adding lanosterol would clear them away. It did.

The team also administered the lanosterol to naturally occurring cataracts in rabbit lenses that had been incubated in lab dishes. That, too, increased the clarity of the lens. Last, the researchers treated dogs with naturally occurring cataracts with a shot of lanosterol in the eye, followed by eyedrops twice a day for six weeks. Again, lens clarity improved.

Khang said that the team next would prepare for human trials, and that he expected toxic effects of lanosterol to be “minimal,” since the substance is already produced by the human body. Bhisitkul said that treatments woudn’t be available until far in the future, but that he thought the greatest opportunity might lie in prevention — that patients might start using an eyedrop when they’re in late middle age, for instance, to prevent cataract formation later on.

In an editorial published with the study in Nature, J. Fielding Hejtmancik of the Ophthalmic Genetics and Visual Function Branch of the National Eye Institute in Rockville, Md., who was not involved in the study, noted that the world’s aging population has been predicted to double the need for cataract surgeries over the next 20 years — making the possibility of a drug-based alternative attractive.

“The potential for this finding to be translated into the first practical pharmacological prevention, or even treatment, of human cataracts could not come at a more opportune time,” he wrote.

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