Using specialized contact lenses to stimulate the brain could offer a novel route to treating depression, preclinical research suggests.
The research, in mice, demonstrates how wearable neuromodulation devices can provide a versatile platform for mood and other brain disorders.
It brings eye-based neurotherapies a step closer towards clinical reality and reveals the feasibility of using contact lenses as a bioelectronic strategy for the treatment of depression.
The findings appear in the latest issue of Cell Reports Physical Science.
“Our work opens up an entirely new frontier of treating brain disorders through the eye,” said lead author Jang-Ung Park, PhD, from 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.”
Depression is increasingly recognized as a disorder involving structural and functional abnormalities in brain networks.
Conventional treatments—such as pharmacological therapy, electroconvulsive therapy, and deep brain stimulation—target these abnormalities but can be invasive and are often limited in their efficacy or tolerability.
Park and team note that the eye provides a compelling gateway for indirect brain modulation due to its embryological derivation from the brain and extensive connectivity.
Studies also suggest that visual impairment with higher prevalence of depression, further recognizing the importance of the eye-brain axis.
To investigate this avenue further, the researchers developed a contact lens that uses transcorneal electrical stimulation (TES) based on temporal interference (TI) to stimulate the brain. This delivers two electrical signals to the retina, which only become active where they intersect, allowing specific areas of the brain to be targeted.
The platform circumvents the invasiveness and limited tolerability of conventional brain stimulation therapies by using the retina as a precise interface for the eye-brain axis.
Electrodes made from ultrathin layers of gallium oxide and platinum allow the lens to be flexible and transparent, conforming to the cornea and preserving natural vision.
The researchers examined the efficacy of the lenses in a stress-induced mouse model that recapitulated key behavioral and biological features associated with depression.
Depressed mice received either no intervention, temporal interference, or the SSRI fluoxetine and were compared with control mice that were not depressed before and after treatment. Machine learning was applied for comprehensive efficacy evaluation.
The team reported that the lenses restored behavioral, neural, and biological deficits in depression.
TI-TES enhanced behavioral resilience, restored prefrontal-hippocampal oscillatory synchrony, and normalized depression-related biomarkers.
When machine-learning integration was used to integrate behavior, brain activity, and biomarkers, it consistently grouped the mice with lenses with the non-depressed control mice rather than the untreated depressed mice.
The researchers acknowledge their research is in its early stages, and that the current study employed a wired configuration to ensure precise waveform control and stimulation stability during proof-of-concept validation.
“Like any new medical technology, our contact lenses will need to go through rigorous clinical evaluation in patients before reaching the market,” said 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.”
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