Electric Eyewear Cheers Up Depressed Mice As Much As Taking Prozac

Efforts to treat academic underperformance in areas with high rates of poverty have found the problem often lies in untreated short-sightedness or poor hearing. In case you are imagining something similar here – that the mice were depressed because they couldn’t see properly – that’s not the case (as delightful as giving mice glasses to make them happier might be). Instead, the contact lenses used in the study contain electrodes that stimulate the retina with weak electrical signals.

The electrical pulses are transmitted to the brain, where they reach regions that have been associated with symptoms of depression in both mice and humans. The electrical stimulation resembles the deep brain stimulation already used to treat a variety of neurological conditions, including depression, but avoids the danger and pain of surgery.

“Our work opens up an entirely new frontier of treating brain disorders through the eye,” said Jang-Ung Park at Yonsei University in South Korea, in a statement. “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.” 

The inspiration for Park and his co-authors’ work is simple: the retinal nerve connects to brain regions that are targeted for implants and antidepressant drugs, but it is much easier to reach. 

“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,” said Park. Contact lenses have been used before for purposes other than vision correction, but usually for diagnoses, for example pressure within the eye or glucose levels.

The lenses are soft yet contain gallium oxide and platinum layers that respond to stimulation at close to 2,000 hertz by generating 0.2 volt electrical signals, which the eye transmits to the retina. The challenge is to create a large effect with very weak electrical activity. 

To do that, the team used interference so that the retina is only activated at a specific location, which can be controlled very precisely. “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.” 

After testing the lenses for safety, the team assessed mice for symptoms similar to depression in humans, looking at behavior such as low activity, blood and brain biomarkers, and brain recordings. The 30 mice deemed to be models of depression were divided into three groups: they gave fluoxetine (Prozac’s active ingredient, an antidepressant in the SSRI class) to one, the contact lenses to another, and left the third group without treatment. After three weeks, each group of mice was assessed in the same way and compared against a control group of non-depressed mice.

Both the SSRIs and contact lenses led to a major improvement on all measures. For example, corticosterone, a brain marker associated with depression, fell 48 percent, while serotonin rose 47 percent in the mice seeing the world through metaphorically rose-colored glasses. 

When placed in a new environment, the treated mice moved 76 percent more in a 10-minute interval and more than doubled their time in the center zone, rather than sticking to the edges as depressed mice often do. They also showed a stronger preference to interact with other mice. These improvements were of the same order as what was experienced by the fluoxetine 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,” said Park. Computer assessments of the mice after treatment grouped them with the mice without depression-like symptoms, rather than with the untreated mice. 

“Like any new medical technology, our contact lenses will need to go through rigorous clinical evaluation in patients before reaching the market,” says Park. There’s probably a bit of work to go, however, before subjects used to moving outside a cage would choose to wear the lenses. “Next, we plan to make the lens fully wireless,” Park said.

After that, the team will “Test …  for long-term safety in larger animals, and personalize the stimulation for each user before advancing into clinical trials in patients.” 

The study is published in Cell Reports Physical Science.