960B Poster - 15. Models of human disease
Friday April 08, 2:00 PM - 4:00 PM

Using optogenetic cardiac pacing and imaging to develop new heart function research platform


Authors:
Elena Gracheva; Fei Wang; Abby Matt; Hongwu Liang; Matthew Fishman; Chao Zhou

Affiliation: Washington University in St Louis

Keywords:
j. cardiovascular disease; b. live imaging

Myocardial infarction remains the leading cause of death and myocardial ischemia contributes to 2/3rds of all cases of heart failure, which is rapidly emerging among the leading causes of mortality and morbidity in the U.S. Drosophila melanogaster is a simple and powerful genetic model system to investigate the role of genes associated with human diseases, including cardiac diseases. As short-lived animals, flies represent an excellent opportunity to model age or disease dependent changes in cardiac function that can be traced throughout life. The fly’s heart tube is located on the dorsal side of its abdomen within 200 μm from the tissue surface allowing visible to near-infrared light to reach the heart tube. This enables non-invasive optical pacing of the fly heart using existing optogenetic tools. Morphological and rhythmic changes in a relatively simple fly heart can be readily analyzed with a non-invasive biomedical imaging technology, Optical Coherence Tomography (OCT). We developed transgenic system consisting of spatiotemporally regulated ChR2, ReaChR, and eNpHR2.0 opsins in Drosophila. We have demonstrated the tissue specific opsin expression and performed the heart pacing experiments. The next step will enable us to characterize changes of the fly heart function in response to different stress challenges providing insights into molecular mechanisms of ischemic preconditioning.