Innovative Light-Sensitive Molecule Enhances Deep Tissue Imaging and Cellular Control in Mice

Researchers at Duke University and the Albert Einstein College of Medicine have developed a groundbreaking method to naturally elevate the levels of a light-sensitive molecule called biliverdin throughout the body. This advancement significantly improves the ability to perform deep tissue imaging, especially in challenging regions like the brain, and expands the potential for using light-based techniques to precisely control cellular functions.

Biliverdin, a biomolecule found in many human and mammalian cells, plays a key role in absorbing near-infrared (NIR) light, which penetrates tissues more effectively than visible light. Although present mostly in blood-rich organs such as the liver and spleen, biliverdin is less abundant in less vascularized organs like the brain. To overcome this, scientists employed a novel technique to inhibit the enzyme biliverdin reductase-A, which normally breaks down biliverdin into bilirubin. Silencing this enzyme led to a natural rise in biliverdin levels throughout the animals, including the brain.

This increase in biliverdin enhanced the effectiveness of optogenetic tools and imaging methods. When used in conjunction with NIR light, these tools became 25 times more efficient at regulating gene expression, and neuronal activation was amplified by a factor of 100 in the brain. As a proof of concept, the team successfully used this approach to stimulate insulin production in a mouse model of type 1 diabetes, reducing blood glucose levels by nearly 60%, marking a significant step toward noninvasive diabetes management.

In addition to cellular control, the elevated biliverdin levels improved deep-tissue imaging capabilities. The researchers utilized photoacoustic tomography to visualize structures up to 7 millimeters deep in the brain—over three times deeper than previous methods—allowing detailed observation of neural activity, blood flow, and vascular networks through the animal’s skull.

This approach opens new doors for studying complex biological processes and diseases in vivo. Verkhusha and Yao are optimistic that their findings will pave the way for future therapies, including long-term disease monitoring and treatment through optogenetics, as well as advanced imaging techniques. Ongoing research aims to explore the use of these tools for studying strokes, neurodegenerative diseases, and other conditions, leveraging the synergy of enhanced tissue penetration and precision control.

While initial studies indicate that manipulating biliverdin reductase-A does not pose significant health risks in animals, further research is needed to evaluate safety in humans. Nonetheless, this innovative strategy holds promise for transforming biomedical research and therapeutic interventions based on deep tissue imaging and light-controlled cellular regulation.