High-content imaging assays to monitor the effects of cigarette smoke on mitochondrial health

Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow obstruction resulting from small airway disease, disappearance of bronchioles and emphysema with the destruction of alveolar walls. In some individuals, dysfunctional mitochondria, unable to indefinitely maintain homeostasis and respond to chronic stress, precipitate changes in epithelial structure and biology that dictate the onset of COPD and disease course.At AstraZeneca, with the aim of disease modification and ultimately cure, we are committed to detecting COPD early and treating the underlying disease drivers. With the work presented, our aim was to develop high-content imaging assays to monitor the effects of cigarette smoke extract (CSE) on mitochondrial health in disease-relevant cells from the lung. AI-based image analysis was used to determine small phenotypic changes of mitochondria.Primary human lung epithelial cells were stimulated with CSE. Mitochondrial changes, including mitochondrial structure networks, reactive oxygen species production, and membrane potential were assessed by live imaging using mitochondrial-specific dyes and confocal microscopy. We could detect an increased production of mitochondrial reactive oxygen species, and changes in mitochondrial membrane potential. Using AI-based image analysis we were also able to find changes in mitochondrial morphology that were directly linked to the level of cigarette smoke exposure.Understanding the effects of CSE on mitoch...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: Mechanisms of lung injury and repair Source Type: research