News release

From: Cell Press

Contact lenses treat depression in mice as effectively as anti-depressant medication

Materials scientists have designed brain-stimulating contact lenses that are as effective as Prozac at treating depression in mice. The soft, transparent contact lenses have in-built electrodes that deliver mild electrical signals to the brain via the retina to stimulate specific brain regions associated with depression. Publishing May 14 in the Cell Press journal Cell Reports Physical Science, the paper shows that depressed mice displayed reduced behavioral, neural, and physiological signs of depression after three weeks of treatment with the contact lenses.

“Our work opens up an entirely new frontier of treating brain disorders through the eye,” says senior author and materials scientist Jang-Ung Park of Yonsei University. “We believe this wearable, drug-free approach holds tremendous promise for transforming how depression and other brain conditions are treated, including anxiety, drug addiction, and cognitive decline.”

Current depression treatments—including drugs, electroconvulsive therapy, and brain implants—work by targeting brain regions and circuits that are associated with mood. Since the retina connects to some of these regions, the researchers wanted to try using the eye as a pathway to stimulate the brain. Previously designed smart contact lenses have been used to monitor eye and metabolic disorders, for example, by measuring eye pressure or glucose levels, but this is the first time contact lenses have been used to treat a brain disorder.

“Because the eye is anatomically a part of the brain, we wondered whether a simple contact lens could serve as a gentle, non-invasive doorway to brain circuits that control mood,” says Park.

The contact lenses stimulate the brain using a method called temporal interference, which delivers two electrical signals to the retina. These electrical signals only become active at their point of intersection, which means that the treatment is very precise in only targeting specific brain regions.

“Think of two flashlights: each beam alone is dim, but where they overlap, a bright spot appears, and that bright spot can be created far away from the flashlights themselves. Our contact lens does the same with two harmless electrical signals,” said Park. “Even though the electrodes sit on the surface of the eye, the signals only become active where they meet at the retina deep inside the eye, gently activating the natural wiring that carries the signal to mood-related brain regions.”

The researchers designed the lenses to be flexible and transparent by building electrodes from ultrathin layers of gallium oxide and platinum and then tested the contact-lens-delivered temporal interference in mice with induced depression. They compared four groups of mice: non-depressed control mice, depressed mice who did not receive any treatment, depressed mice who received temporal interference, and depressed mice who received fluoxetine, a selective serotonin reuptake inhibitor (SSRI) and the active ingredient in Prozac. To assess the mice’s depression before and after treatment, the team used behavioral assays, electrophysiological brain recordings, and measured blood and brain biomarkers associated with depression.

The contact lens treatment reduced signs of depression in all three categories. Mice that received temporal interference stimulation for 30 minutes per day for three weeks showed behavioral improvements that were comparable with mice who received fluoxetine. Recordings of brain activity revealed that the treatment restored connectivity between the hippocampus and prefrontal cortex that was lost due to depression. The treatment also partially restored the levels of biomarkers associated with depression, including reduced levels of inflammatory molecules in the brain, a 48% reduction in blood corticosterone, and a 47% increase in serotonin levels compared to the untreated depressed mice.

“We were struck that improvements appeared together across behavior, brain activity, and biology and that the effect was comparable to a widely used antidepressant drug,” says Park.

When the researchers asked a machine learning model to group the mice based on their behavior, brain activity, and biomarker levels, the model consistently grouped mice in the contact lens treatment group with non-depressed control mice rather than with mice in the untreated depression group.

“Like any new medical technology, our contact lenses will need to go through rigorous clinical evaluation in patients before reaching the market,” says Park. “Next, we plan to make the lens fully wireless, test it for long-term safety in larger animals, and personalize the stimulation for each user before advancing into clinical trials in patients.”