Eye-opening discovery about the adult brain’s ability to restore vision

A discovery about how some visually impaired adults might begin to see offers a new perspective on the brain’s possibilities. The finding that the adult brain has the potential to partially recover from hereditary blindness comes from a collaboration between researchers at the University of California, the Irvine School of Biological Sciences and the School of Medicine. Your paper appears in Current Biology.¹

According to a press release, the team was studying treatment for liver congenital amaurosis, known as LCA. The term refers to a group of inherited retinal disorders characterized by severe visual impairment at birth. The condition, which results from mutations in one of over two dozen genes, causes degeneration, or malfunction, of the retina’s photoreceptors.

The university noted that the researchers found that by administering chemical compounds that target the retina, called synthetic retinoids, they were able to restore a remarkable amount of vision in children with LCA. The UCI team wanted to see if treatment could make a difference for adults with the condition.

“Honestly, we were blown away by how much the treatment saved brain circuits involved in vision,” said Sunil Gandhi, professor of neurobiology and behavior and corresponding author. Gandhi is a Fellow of the UCI Center for the Neurobiology of Learning and Memory and a Fellow of the Center for Translational Vision Research. “There is more to seeing than an intact and functioning retina. It starts in the eye, which sends signals through the brain. It is in the central circuits of the brain where visual perception actually occurs.”

Until now, scientists believed that the brain had to receive these signals in infancy in order for central circuits to connect properly.

Working with LCA rodent models, the collaborators were surprised by what they found.

“Central visual pathway signaling has been significantly restored in adults, particularly the circuits that deal with information coming from both eyes,” Gandhi said in the press release. “Immediately after treatment, signals from the opposite eye, which is the dominant signaling pathway in the mouse, activated twice as many neurons in the brain.”

However, Gandhi noted in the press release that what was even more stunning was that the signals coming from the equilateral orbital pathway activated five times more neurons in the brain after the treatment, and this impressive effect was long-lasting.

“The recovery of visual function at the brain level was much greater than expected based on the improvements we saw at the retinal level,” Gandhi said in the press release. “The fact that this treatment works so well in adulthood on the central visual pathway supports a new concept that there is latent visual potential just waiting to be triggered.”

According to the press release, the finding expands a range of research avenues.

“Every time you make a discovery that breaks with your expectations about the brain’s ability to adapt and rewire, it teaches you a broader concept,” Gandhi said. “This new paradigm could aid in the development of retinoid therapies to more completely salvage the central visual pathway in adults with this condition.”

Gandhi and first author Carey Huh, PhD, who initiated the project, teamed up with Krzysztof Palczewski, Distinguished Professor of Ophthalmology. Palczewski, director of the Center for Translational Vision Research, is known for his work on retinoids and the visual cycle. Philip Kiser, associate professor of physiology and biophysics, an expert in the biochemistry of the visual cycle, helped lead the group. Kiser, who holds a joint post in ophthalmology, is a member of the Center for Translational Vision Research.

The research was funded by the National Institutes of Health, the Department of Veterans Affairs, and the Research to Prevent Blindness Foundation.

Relation

Sunil Gandhi; Carey Huh.; Krzysztof Palczewski; Henri Leinonen; Taylor Nakayama, Julia R. Tomasello, et al. Retinoid therapy restores eye-specific cortical responses in adult mice with retinal degeneration. Current Biology. Published September 23, 2022. DOI: https://doi.org/10.1016/j.cub.2022.09.005