Zebrafish model of photochemical thrombosis for translational research and thrombolytic screening in vivo. Issue 4 (13th May 2016)

• Record Type: Journal Article
• Authors: Lee, I‐Ju; Yang, Yi‐Cyun; Hsu, Jia‐Wen; Chang, Wei‐Tien; Chuang, Yung‐Jen; Liau, Ian
• Is Part Of: Journal of biophotonics. Volume 10:Issue 4(2017)
• Page Start: 494
• Page End: 502
• Publication Date: 2016-05-13
• Subjects: zebrafish -- photochemistry -- thrombosis -- thrombolysis -- drug screen; Photonics -- Periodicals; Optical materials -- Periodicals; Optics -- Periodicals; Medical instruments and apparatus -- Periodicals; 621.3605
• DOI: 10.1002/jbio.201500287
• Languages: English
• ISSNs: 1864-063X

Abstract

Abstract : Acute thromboembolic diseases remain the major global cause of death or disability. Although an array of thrombolytic and antithrombotic drugs has been approved to treat or prevent thromboembolic diseases, many more drugs that target specific clotting mechanisms are under development. Here a novel zebrafish model of photochemical thrombosis is reported and its prospective application for the screening and preclinical testing of thrombolytic agents in vivo is demonstrated. Through photochemical excitation, a thrombus was induced to form at a selected section of the dorsal aorta of larval zebrafish, which had been injected with photosensitizers. Such photochemical thrombosis can be consistently controlled to occlude partially or completely the targeted blood vessel. Detailed mechanistic tests indicate that the zebrafish model of photochemical thrombosis exhibits essential features of classical coagulation and a thrombolytic pathway. For demonstration, tissue plasminogen activator (tPA), a clinically feasible thrombolytic agent, was shown to effectively dissolve photochemically induced blood clots. In light of the numerous unique advantages of zebrafish as a model organism, our approach is expected to benefit not only the development of novel thrombolytic and antithrombotic strategies but also the fundamental or translational research targeting hereditary thrombotic or coagulation disorders. Abstract : A zebrafish model of photochemical thrombosis is presented. With the numerous inherent advantages of zebrafish (such as high degree of genetic conservation, low maintenance cost, ease of genetic manipulation, and convenience of administrating drugs), such approach is expected to facilitate not only translational research on arterial thrombotic disorders but also the screening of novel thrombolytic and antithrombotic agents on a large scale and with high throughput.