Alcohol drug restores vision loss from macular degeneration in mice

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Researchers may have found a way to revive some vision loss caused by age-related macular degeneration and the inherited condition retinitis pigmentosa.

Age-related macular degeneration is the leading cause of blindness. Retinitis pigmentosa (RP) is a rare genetic disease that causes retinal cell breakdown and loss.

Disulfiram, a drug marketed under the brand name Antabuse, used to treat alcoholism, could be the key to restoring this vision loss.

“We knew that the pathway that the drug disulfiram blocks to treat alcoholism was very similar to the pathway that is hyper-activated in degenerative blindness,” says Michael Telias, assistant professor of ophthalmology, neuroscience, and Science Center visuals of the University. from Rochester Medical Center. Telias is the first author of the article in Scientists progress.

“We expected some improvement, but our results exceeded our expectations. We saw vision that had been lost for a long period of time retained in those who received the treatment.

In research involving mice, researchers found that disulfiram helped restore some vision by suppressing sensory noise in the inner retina caused by the death of photoreceptors in the outer retina which is caused by the progression of outer retinal degeneration (such as age-related macular degeneration or retinitis). pigmentosa), in which light-sensitive cells called “photoreceptors” slowly die off over the years.

In previous research as a postdoctoral fellow at the University of California, Berkeley, Telias discovered that when photoreceptors die, it disrupts the function of the inner retina. This causes sensory noise which eventually becomes a barrier between surviving photoreceptors and the brain.

This latest research, led by Richard Kramer, a professor at the University of California, Berkeley, and Michael Goard, an assistant professor at the University of California, Santa Barbara, found that disulfiram can target this sensory noise, allowing surviving photoreceptors of the outer retina to complete the signal to the brain and ultimately restore some vision. They found that near-blind mice treated with disulfiram were much better at detecting images on a computer screen.

“The treated mice really see better than the unmedicated mice. These particular mice could barely detect images at this advanced stage of degeneration. I think it’s quite dramatic,” says Kramer.

“If a visually impaired human were given disulfiram and their vision improved even a little, that would be a great result in itself. But it would also strongly implicate the retinoic acid pathway in vision loss. And it would be an important proof of concept that could lead to the development of new drugs and a whole new strategy to help improve vision.

The researchers plan to partner with ophthalmologists to conduct a clinical trial of disulfiram in patients with RP. The trial would be carried out on a small group of people with advanced, but not yet complete, retinal degeneration.

Disulfiram has serious side effects if alcohol is consumed while taking it, including headache, nausea, muscle cramps, and flushing. But if disulfiram can improve vision, more targeted therapies could be sought that do not interfere with alcohol breakdown or other metabolic functions.

Researchers have previously tested an experimental drug called BMS 493 that inhibits the retinoic acid receptor, and they have also used gene therapy to knock down the receptor. Both of these procedures also significantly improved vision in mice with RP.

Other co-authors are from the University of California at Santa Barbara and the University of California at Berkeley. The National Institutes of Health and the National Science Foundation funded the work.

Source: University of Rochester

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