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Here, we characterize cardiac regeneration from cardiomyocyte chemoptogenetic ablation caused by localized near\u2010infrared excited photosensitizer\u2010mediated reactive oxygen species (ROS) generation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Exposure of transgenic adult zebrafish, <jats:italic>Tg(myl7:fapdl5\u2010cerulean)<\/jats:italic>, to di\u2010iodinated derivative of the cell\u2010 permeable Malachite Green ester fluorogen (MG\u20102I) and whole\u2010body illumination with 660\u2009nm light resulted in cytotoxic damage to about 30% of cardiac tissue. After chemoptogenetic cardiomyocyte ablation, heart function was compromised, and macrophage infiltration was detected, but epicardial and endocardial activation response was much muted when compared to ventricular amputation. The spared cardiomyocytes underwent proliferation and restored the heart structure and function in 45\u201360\u2009days after ablation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This cardiomyocyte ablation system did not appear to activate the epicardium and endocardium as is noted in other cardiac injury models. This approach represents a useful model to study specifically cardiomyocyte injury, proliferation and regeneration in the absence of whole organ activation. Moreover, this system can be adapted to ablate distinct cell populations in any organ system to study their function in regeneration.<\/jats:p><\/jats:sec>","DOI":"10.1002\/dvdy.305","type":"journal-article","created":{"date-parts":[[2021,1,27]],"date-time":"2021-01-27T02:05:27Z","timestamp":1611713127000},"page":"986-1000","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Zebrafish heart regenerates after chemoptogenetic cardiomyocyte depletion"],"prefix":"10.1002","volume":"250","author":[{"given":"Maria A.","family":"Missinato","sequence":"first","affiliation":[{"name":"Department of Developmental Biology School of Medicine, University of Pittsburgh  Pittsburgh Pennsylvania USA"},{"name":"Avidity Biosciences, Inc.  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel A.","family":"Zuppo","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology School of Medicine, University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon C.","family":"Watkins","sequence":"additional","affiliation":[{"name":"Department of Cell Biology Center for Biologic Imaging, School of Medicine, University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel P.","family":"Bruchez","sequence":"additional","affiliation":[{"name":"Department of Chemistry Carnegie Mellon University  Pittsburgh Pennsylvania USA"},{"name":"Department of Biological Sciences Molecular Biosensor and Imaging Center, Carnegie Mellon University  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7123-0063","authenticated-orcid":false,"given":"Michael","family":"Tsang","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology School of Medicine, University of Pittsburgh  Pittsburgh Pennsylvania 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