The key to restoring vision may be held in drugs that treat alcoholism

Researchers have revived age-related macular degeneration, the main cause of blindness, and vision loss caused by retinitis pigmentosa (RP), a rare genetic disorder that causes the destruction and loss of retinal cells. You may have found a way. .. Disulfiram (sold under the brand name Antabuse), which is used to treat alcoholism, may hold the key to relieving this loss of vision.

Dr. Michael Terias

“We knew that the pathways that disulfiram blocks to treat alcoholism are very similar to the pathways that are overactivated in degenerative blindness,” he said. Dr. Michael TeriasAssociate Professor, Center for Ophthalmology, Neuroscience, and Visual Science, University of Rochester Medical Center, and lead author of the paper published today Science Advances.. “We were expecting some improvement, but our findings exceeded our expectations. Those who received treatment retained their long-term loss of vision. I saw it. “

In studies on mice, researchers found that disulfiram produced sensory noise in the inner retina caused by the death of photoreceptors in the outer retina caused by the progression of lateral retinal degeneration (such as age-related macular degeneration and retinitis pigmentosa). Retinitis pigmentosa, in which photoreceptor cells called “photoreceptors” die slowly over the years, have been found to help restore vision by suppressing them). In past studies, as a postdoctoral fellow at UC Berkeley, Terias discovered that when photoreceptors die, they destroy function in the retina. This causes sensory noise that ultimately becomes a barrier between the surviving photoreceptors and the brain. This latest study, led by Dr. Richard Kramer., Professor of the University of California, Berkeley, and Associate Professor Michael Goard of the University of California, Santa Barbara, discovered that disulfiram can target its sensory noise and that surviving photoreceptors outside the retina can complete the signal. Restores some vision to the brain and finally. They found that nearly blind mice treated with disulfiram were much better at detecting images on computer screens.

Mouse retinal ganglion cells (green) that are hyperactive due to degenerative visual impairment. Other retinal cell types are labeled blue. Hyperactivity disorder interferes with the proper transmission of signals from the retina to the brain. Richard Kramer’s lab at the University of California, Berkeley discovered the cause of hyperactivity, identified drugs that interfered with the process, and improved vision by doing so. (Image credit: Shubhash Yadav, Kramer Lab)

“Treatd mice look really better than non-drug mice. These particular mice could barely detect images in the late stages of this degeneration.” Kramer said, “It’s very dramatic. “I think it’s a good idea,” he said. “If you administer disulfiram to a person with visual impairment and your vision improves even a little, it will have great results in itself. But it is also in the retinoic acid pathway in vision loss. It will be strongly relevant, and it will be an important conceptual demonstration that has the potential to drive entirely new strategies to support the development of new drugs and the improvement of vision. “

Researchers are planning to partner with an ophthalmologist to conduct clinical trials of disulfiram in patients with RP. The study will be conducted on a small number of people with advanced but not yet complete retinal degeneration. Disulfiram has serious side effects such as headache, nausea, muscle cramps and flushing when alcohol is consumed while drinking. However, if disulfiram can improve vision, it can look for more targeted treatments that do not interfere with alcohol breakdown or other metabolic functions. Researchers have already tested an drug named BMS 493 that blocks the receptor for retinoic acid and are using gene therapy to knock down the receptor. Both of these procedures dramatically improved the visual acuity of RP mice.

Other authors include Kevin Sit, Ph.D., Daniel Frozenfar, Benjamin Smith, co-lead authors at the University of California, Santa Barbara, and Arjit Misra at the University of California, Berkeley. This work was funded by the National Institutes of Health and the National Science Foundation.