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2022/07/02

High-Content Functional Screening for Oncocardiology Using Novel Translucent Cardiac Fluorescent Protein Transgenic Zebrafishes

Zebrafish symposium of the 49th JSOT conference @ Sapporo.
The schedule was decided on Saturday, July 2, 2022 (third day of the conference) from 9:00 to 11:30.July 2, 2022, 9: 00-11: 30 (JST).

High-Content Functional Screening for Oncocardiology Using Novel Translucent Cardiac Fluorescent Protein Transgenic Zebrafishes
Toshio Tanaka 1,2,* ,Kayoko Yamada 1,2,Aoi Mori 1,2,Rino Sawada 1,2,Kyoko Yamamoto 1,2 ,Yuka Mizutani 1,2,Noriko Umemoto 1,Yasuhito Shimada 3,Yuhei Nishimura 3
1 Department of Systems Pharmacology Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan
2 Mie University Medical Zebrafish Research Center, Tsu, Mie 514-8507, Japan
3 Department of Integrative Pharmacology Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan

Oncocardiology has gained interest in recent years due to a remarkable increase in the number of new anticancer drugs causing cardiotoxicity. The zebrafish provided an excellent platform to study the genetic and molecular approach of cardiotoxicology. Tools to improve the preclinical study of many new therapeutic compounds are essential for the timely identification of those that are potentially cardiotoxic in clinical treatment. Therefore, a key challenge in the cardiac functional assessment of cardiac imaging disturbances with many anticancer drugs in zebrafish has been the development of a high-content screening system. The method made use of a transparent, transgenic lines of zebrafish expressing fluorescent proteins in the ventricular myocardium. The high content images were automatically captured during ventricular movement in day 4 post-fertilization larvae and were used to calculate systolic ventricular diameters (VDs) and diastolic ventricular diameters (VDd) previously reported (Mol Biotechnol.2013 55:131-42). These changes in imaging with each anticancer drug were found to correlate with the clinical cardiotoxicology of each anticancer drug in this study (Toxicol Sci.2015 143:374-84). This high content method was expressing fluorescent proteins in the ventricular myocardium. faster than conventional manual assessment in determining the cardiotoxicity of a broad range of chemotherapeutic agents and completely reproduced the results of the conventional manual system. The high throughput of the automated high content system favors its use over the current manual approaches to oncocardiology.