New imaging technique sheds light on zebrafish and heart disease
A new type of microscopy is helping scientists study the regenerative hearts of zebrafish.
For the first time, a new imaging technique has been able to capture extremely detailed 3D video images of growing zebrafish hearts. Unlocking the secrets of zebrafish heart formation through these detailed images could, in turn, reveal more about how human hearts grow and heal.
Zebrafish hearts are commonly used in cardiac research as models for the human heart. Interestingly, while they are similar to human hearts, zebrafish hearts have the added ability to regenerate and heal themselves after injury. Collaborating researchers from the Centre for Cardiovascular Science and the University of Glasgow’s School of Physics and Astronomy hope that by providing incredibly detailed time-lapse videos of growing zebrafish hearts, we can better understand the cellular and subcellular processes by which these hearts form and repair themselves.
The Difficulty with Imaging Zebrafish
Imaging zebrafish hearts comes with complications. Zebrafish embryos’ hearts move incredibly quickly, beating three times per second. The constant movement has made it difficult to accurately capture images of these hearts in 3D.
By the time you’ve taken an image of one layer of the heart, it has moved on to another part of its cardiac cycle. To add to the challenge, heart cells can be damaged by over-exposure to laser light that is needed for fluorescence imaging.
While some 3D images of beating zebrafish hearts have been captured before, cardiac researchers have struggled to create useful 3D time-lapse videos of the heart growing over the course of a full day.
The New Imaging Technique
The new imaging technique uses a computer programme to calculate exactly when to fire lasers at a beating heart.
Our microscope uses visible light to ‘watch’ the beating heart of the zebrafish through its transparent skin, allowing our computer programs to know exactly when to selectively fire laser light at the heart to capture specific moments in its cycle.
This precision allows researchers to study individual heart cells continuously forming and dividing over a full-day period, without causing any harm to the fish. The new approach has provided a way to visualise biological processes, like cell division within the heart, which have never been seen before.
New Potential Treatments
The newly developed fluorescence time-lapse imaging technique uses a very thin sheet of laser light to build up images into a full 3D image of the heart layer by layer. This technique brings together physics, engineering, and heart research to display live processes of heart formation.
Co-author Dr Martin Denvir points out two promising potential applications of the new imaging technique.
Firstly, now that we can see detailed images of the growth of the heart on a cellular level, we hope to be able to apply that new knowledge to develop treatments for abnormal heart formation in the future.
Secondly, we’ve been able to observe immune cells travelling to injured areas of the heart, which could help us guide the modification of immune response to more effectively treat cardiac inflammation and heart disease.
The broader applications will enable new insights into a wide range of biological mechanisms, especially where movement and changes of shape have previously made long term imaging extremely challenging. The vision of the British Heart Foundation to enable such innovative collaborations will continue to transform our understanding of the cardiovascular system.
The paper, titled ‘Adaptive prospective optical gating enables day-long 3D time-lapse imaging of the beating embryonic zebrafish heart’, is published in Nature Communications and is available online at (https://doi.org/10.1038/s41467-019-13112-6). The research was supported with funding from the British Heart Foundation (New Horizons award), the Engineering and Physical Sciences Research Council, the Royal Society of Edinburgh.
Funding for the single plane illumination microscope (SPIM) and advanced transgenic zebrafish used in these studies was provided by The BHF Centre of Research Excellence Award, University of Edinburgh.