Department of Developmental Biology, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Avidity Biosciences, Inc., La Jolla, California, USA.
Dev Dyn. 2021 Jul;250(7):986-1000. doi: 10.1002/dvdy.305. Epub 2021 Feb 8.
Zebrafish can regenerate adult cardiac tissue following injuries from ventricular apex amputation, cryoinjury, and cardiomyocyte genetic ablation. Here, we characterize cardiac regeneration from cardiomyocyte chemoptogenetic ablation caused by localized near-infrared excited photosensitizer-mediated reactive oxygen species (ROS) generation.
Exposure of transgenic adult zebrafish, Tg(myl7:fapdl5-cerulean), to di-iodinated derivative of the cell- permeable Malachite Green ester fluorogen (MG-2I) and whole-body illumination with 660 nm 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 45-60 days after ablation.
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.
斑马鱼可以在心室尖切除、冷冻损伤和心肌细胞基因消融等损伤后再生成年心脏组织。在这里，我们描述了由局部近红外激发光敏剂介导的活性氧（ROS）产生引起的心肌细胞光遗传学消融导致的心脏再生。
暴露于二碘化衍生物的转基因成年斑马鱼，Tg（myl7：fapdl5-cerulean），细胞通透的孔雀石绿酯荧光染料（MG-2I）和全身用 660nm 光照射导致约 30%的心脏组织细胞毒性损伤。在化学消融心肌细胞后，心功能受损，并检测到巨噬细胞浸润，但与心室切除相比，心外膜和心内膜的激活反应要弱得多。在消融后 45-60 天，保留的心肌细胞增殖并恢复了心脏结构和功能。
这种心肌细胞消融系统似乎没有激活心外膜和心内膜，如其他心脏损伤模型中所观察到的那样。这种方法代表了一种有用的模型，可以在没有整个器官激活的情况下专门研究心肌细胞损伤、增殖和再生。此外，该系统可以适应于任何器官系统中消融不同的细胞群体，以研究它们在再生中的功能。
