Integrating 4-D light-sheet fluorescence microscopy and genetic zebrafish system to investigate ambient...

Ambient air pollutants, including PM_2.5 (aerodynamic diameter d ~2.5 μm), PM₁₀ (d ~10 μm), and ultrafine particles (UFP: d < 0.1 μm) impart both short- and long-term toxicity to various organs, including cardiopulmonary, central nervous, and gastrointestinal systems. While rodents have been the principal animal model to elucidate air pollution-mediated organ dysfunction, zebrafish (Danio rerio) is genetically tractable for its short husbandry and life cycle to study ambient pollutants. Its electrocardiogram (ECG) resembles that of humans, and the fluorescent reporter-labeled tissues in the zebrafish system allow for screening a host of ambient pollutants that impair cardiovascular development, organ regeneration, and gut-vascular barriers. In parallel, the high spatiotemporal resolution of light-sheet fluorescence microscopy (LSFM) enables investigators to take advantage of the transparent zebrafish embryos and genetically labeled fluorescent reporters for imaging the dynamic cardiac structure and function at a single-cell resolution. In this context, our review highlights the integrated strengths of the genetic zebrafish system and LSFM for high-resolution and high-throughput investigation of ambient pollutants-mediated cardiac and intestinal toxicity.