Hardman Ron C, Kullman Seth W, Hinton David E
Duke University, Environmental Sciences and Policy Division, Nicholas School of the Environment and Earth Sciences, LSRC A333, Durham, NC, USA.
Comp Hepatol. 2008 Oct 6;7:7. doi: 10.1186/1476-5926-7-7.
A novel transparent stock of medaka (Oryzias latipes; STII), recessive for all pigments found in chromatophores, permits transcutaneous imaging of internal organs and tissues in living individuals. Findings presented describe the development of methodologies for non invasive in vivo investigation in STII medaka, and the successful application of these methodologies to in vivo study of hepatobiliary structure, function, and xenobiotic response, in both 2 and 3 dimensions.
Using brightfield, and widefield and confocal fluorescence microscopy, coupled with the in vivo application of fluorescent probes, structural and functional features of the hepatobiliary system, and xenobiotic induced toxicity, were imaged at the cellular level, with high resolution (< 1 microm), in living individuals. The findings presented demonstrate; (1) phenotypic response to xenobiotic exposure can be investigated/imaged in vivo with high resolution (< 1 microm), (2) hepatobiliary transport of solutes from blood to bile can be qualitatively and quantitatively studied/imaged in vivo, (3) hepatobiliary architecture in this lower vertebrate liver can be studied in 3 dimensions, and (4) non invasive in vivo imaging/description of hepatobiliary development in this model can be investigated.
The non-invasive in vivo methodologies described are a unique means by which to investigate biological structure, function and xenobiotic response with high resolution in STII medaka. In vivo methodologies also provide the future opportunity to integrate molecular mechanisms (e.g., genomic, proteomic) of disease and toxicity with phenotypic changes at the cellular and system levels of biological organization. While our focus has been the hepatobiliary system, other organ systems are equally amenable to in vivo study, and we consider the potential for discovery, within the context of in vivo investigation in STII medaka, as significant.
一种新型的青鳉透明品系（Oryzias latipes；STII），其色素细胞中的所有色素均为隐性，可对活体个体的内部器官和组织进行经皮成像。本文介绍了在STII青鳉中进行非侵入性体内研究方法的开发，以及这些方法在二维和三维肝胆结构、功能及异生素反应体内研究中的成功应用。
使用明场、宽场和共聚焦荧光显微镜，结合荧光探针的体内应用，在活体个体中以高分辨率（<1微米）在细胞水平上对肝胆系统的结构和功能特征以及异生素诱导的毒性进行了成像。本文的研究结果表明：（1）可在体内以高分辨率（<1微米）研究/成像异生素暴露后的表型反应；（2）可在体内定性和定量地研究/成像溶质从血液到胆汁的肝胆转运；（3）可在三维空间中研究这种低等脊椎动物肝脏的肝胆结构；（4）可研究该模型中肝胆发育的非侵入性体内成像/描述。
所描述的非侵入性体内方法是在STII青鳉中以高分辨率研究生物结构、功能和异生素反应的独特手段。体内方法还为将疾病和毒性的分子机制（如基因组学、蛋白质组学）与生物组织细胞和系统水平的表型变化相结合提供了未来机会。虽然我们的重点是肝胆系统，但其他器官系统同样适合进行体内研究，并且我们认为在STII青鳉体内研究的背景下发现的潜力巨大。
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