OxyBLI: A Genetics-Based Approach for In Vivo Real-Time Visualization of Tissue Oxygenation Dynamics

Accurate measurement of cellular oxygen levels is essential for understanding the balance between oxygen demand and supply in tissues. However, conventional methods only yield compromised results. We harnessed the oxygen dependence of bioluminescence to develop OxyBLI--a noninvasive optical method that directly monitors oxygen levels in specific cell populations of intact experimental animals. We characterized OxyBLI signals across various critical situations associated with common interventions. Hypoxic breathing and subsequent systemic tissue hypoxia caused blood to be redistributed in a way that prioritized brain oxygenation. In contrast, hyperoxic breathing sharply increased tissue oxygenation, which promptly returned to the target level owing to a vasoconstrictor response. These findings are expected to help resolve the long-standing clinical issue regarding the risks and benefits of administering supplemental oxygen to acutely ill patients. Our multifaceted approach, which presents multiple challenges to individual animals over time, will advance our understanding of the delicate interaction between hypoxia and hyperoxia.