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    Researchers enhanced near-infrared (NIR) probes and optogenetic tools using a biliverdin reductase-A knock-out model. This boosts performance for deep-tissue imaging and optogenetic therapy in vivo.

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    Area of Science:

    • Biomedical Engineering
    • Optogenetics
    • Molecular Imaging

    Background:

    • Bacteriophytochrome-based near-infrared (NIR) probes and optogenetic tools offer potential for biological research and therapy.
    • Existing NIR systems face limitations in performance and depth penetration for in vivo applications.

    Purpose of the Study:

    • To develop enhanced NIR photoacoustic and fluorescence probes and optogenetic tools.
    • To improve the performance of these tools using a biliverdin reductase-A knock-out (Blvra-/-) model.
    • To demonstrate the therapeutic potential of these enhanced systems for conditions like diabetes.

    Main Methods:

    • Development of NIR probes and optogenetic tools derived from bacteriophytochromes.
    • Utilized a Blvra-/- mouse model to enhance endogenous biliverdin chromophore levels.
    • Employed 3D photoacoustic, ultrasound localization microscopy, and two-photon fluorescence imaging techniques.
    • Evaluated light-controlled gene expression and in vivo glucose reduction in a diabetes model.

    Main Results:

    • The Blvra-/- model significantly enhanced the performance of NIR constructs, with up to 25-fold improvement in light-controlled transcription.
    • Optogenetic activation in Blvra-/- neurons showed a 100-fold increase compared to wild-type.
    • In vivo studies demonstrated a ~60% reduction in blood glucose levels in diabetic Blvra-/- mice.
    • Achieved deep-tissue imaging up to 7 mm in the brain using simultaneous photoacoustic and ultrasound microscopy.

    Conclusions:

    • The Blvra-/- model is a promising platform for enhancing biliverdin-dependent NIR systems.
    • These advanced tools show significant potential for deep-tissue biological interrogation and optogenetic therapy.
    • The developed systems overcome depth limitations, enabling unprecedented in vivo imaging and manipulation capabilities.