Antabuse may help revive vision in people with progressive blinding disorders

Test of drug could prove role of hyperactive retinal cells in blindness, potentially leading to better therapies




Richard Kramer, Michael Goard, Michael Telias, Daniel Frozenfar, Benjamin Smith and Arjit Misra | UC Berkeley


Summary: Animal and cell studies show that as retinal cells die in degenerative eye diseases, they make other cells hyperactive, creating noise that further obscures vision. Tests to prove this in humans are hard to conduct, however. Antabuse, an approved drug used to wean people off alcohol, should tamp down this hyperactivity and conclusively show whether hyperactivity plays a role in humans, potentially driving work to find better drugs to help those with progressive vision loss.


Introduction

Researchers at the University of California, Berkeley, have found that a drug once widely used to wean alcoholics off of drinking helps to improve sight in mice with retinal degeneration.

The drug may revive sight in humans with the inherited disease retinitis pigmentosa (RP), and perhaps in other vision disorders, including age-related macular degeneration. A group of scientists led by Richard Kramer, UC Berkeley professor of molecular and cell biology, had previously shown that a chemical -- retinoic acid -- is produced when light-sensing cells in the retina, called rods and cones, gradually die off. This chemical causes hyperactivity in retinal ganglion cells, which ordinarily send visual information to the brain. The hyperactivity interferes with their encoding and transfer of information, obscuring vision.


He realized, however, that the drug disulfiram -- also called Antabuse -- inhibits not only enzymes involved in the body's ability to degrade alcohol, but also enzymes that make retinoic acid. In new experiments, Kramer and collaborator Michael Goard, who directs a lab at UC Santa Barbara (UCSB), discovered that treatment with disulfiram decreased the production of retinoic acid and made nearly-blind mice much better at detecting images displayed on a computer screen.



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Story Source: Materials provided by University of California - Berkeley. Original written by Robert Sanders. Note: Content may be edited for style and length.

Journal Reference:

  1. Michael Telias, Kevin K. Sit, Daniel Frozenfar, Benjamin Smith, Arjit Misra, Michael J. Goard and Richard H. Kramer. Retinoic acid inhibitors mitigate vision loss in a mouse model of retinal degeneration. Science Advances, 2022 DOI: 10.1126/sciadv.abm4643