A small glass window implanted in a mouse’s abdomen now lets scientists watch liver and kidney fibrosis unfold over weeks instead of hours. Fibrosis—the buildup of stiff scar tissue that replaces healthy cells—drives organ failure in diseases like cirrhosis and chronic kidney disease, but its slow progression has made it nearly impossible to study directly. Standard microscopy can only peer about a millimetre into tissue, and exposing internal organs for imaging requires invasive surgery that limits observation to a day or two. The abdominal imaging window sidesteps both limits, allowing repeated, non-invasive imaging of the same organ over weeks. The researcher has also created genetically modified mice whose scar-forming cells (pericytes and myofibroblasts) glow without added dyes, and will combine these with label-free imaging techniques that reveal collagen networks at high resolution. This will test whether the collagen mesh itself controls whether myofibroblasts proliferate, migrate, or revert to a resting state. If it does, targeting the physical structure of scar tissue—rather than just the cells that build it—could open new routes to halt or reverse fibrosis. This is fundamental science: understanding a basic mechanism of tissue repair that has been invisible until now.
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Recent advances in intravital microscopy (IVM) have enabled scientists to challenge longstanding dogmas and address new hypotheses by direct in situ observation. Critically, IVM allows dynamic imaging of complex biological processes in real time. Most IVM techniques are based on fluorescent microscopy, however light scattering limits the maximum imaging depth to 1mm. Consequently, organ visualisation has been restricted to superficial tissue such as the skin or to surgically exposed organs. Orga n exposure requires invasive surgery and manipulation of organs from their anatomical positions, limiting IVM duration to 24-36 hours. However, fibrogenesis takes place over significantly longer time periods. Recently, an abdominal imaging window (AIW) technique has been developed in mice, allowing long-term sequential imaging of previously inaccessible organs, and over the past six months I have successfully set up the AIW technique in Edinburgh. Key goals are: To investigate in vivo, the cellular mechanisms regulating liver and kidney fibrosis using AIWs and multiple imaging modalities (multiphoton microscopy, second harmonic generation (SHG) microscopy and Coherent anti-Stokes Raman spectroscopy). I have recently generated mice that allow specific, label-free imaging in vivo of pericytes and myofibroblasts (the major source of collagen during fibrosis) for the first time. By combining these mouse reporter lines with SHG microscopy (SHG does not require exogenous labeling and a llows visualisation of collagen networks at very high resolution), I will address the central hypothesis that collagen networks are critical regulators of myofibroblast fate, by examining key myofibroblast biological processes mechanistically including migration, expansion, differentiation and reversion in real-time in vivo.
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