Wnt信号通路在重离子辐照诱导的斑马鱼视觉损伤中的调控机制

In space, heavy-ion irradiation is a harmful factor to astronauts’ health, especially to the visual system of astronauts. Therefore, it is necessary to research on the visual damage induced by the heavy-ion irradiation. Previous studies have reported that ionizing radiation with low-LET can caused a number of optic complications, including cataract formation, retinal or atrophy degeneration. For embryos, ionizing radiation may disrupt the differentiation of the retinal and led to the microphthalmia. However, there are few studies about the visual damage induced by heavy-ion irradiation and the molecular mechanism regulating the heavy-ion induced visual damage is unclear. During the development of the eyes, Wnt signaling pathway play important roles in the regulation of developing retina, cornea and lens. Zebrafish has been taken as a model organism for eye development and diseases research for its special advantage. Early research has approved that heavy ion could cause continuous cell apoptosis and decrease of photoreceptive function in zebrafish eyes. Heavy ion could also cause the decrease of cell density in retinal cell layers and significant decrease of some photoreceptive development-related genes. This research will Screen the key genes in Wnt signaling pathway that correlated with abnormal developmental of zebrafish visual system after heavy-ion irradiation using gene chip technology and investigate on the regulating mechanism of Wnt signaling pathway in irradiation-induced visual damage.

在空间环境中，重离子是影响宇航员健康的主要因素，重离子辐射对于宇航员视觉神经的影响最为显著，因此开展重离子辐射诱导视觉损伤的相关研究变得非常必要。已有研究表明低LET的电离辐射可以引起白内障、视网膜和视神经萎缩等多种眼部并发症，还可能影响胚胎视网膜分化导致小眼畸形。但目前对于重离子诱导的视觉损伤研究很少，分子机制也还不明确。Wnt信号通路在眼部发育过程中，对视网膜、角膜和晶体发育调控都起重要作用。模式生物斑马鱼由于其独特的优势，已经广泛应用与视觉发育及疾病的相关研究。前期实验已经证实重离子辐射可以导致斑马鱼眼部持续的细胞凋亡，而且辐照后斑马鱼感光功能也受到了一定的影响，视网膜细胞密度降低，部分与感光功能发育相关基因表达显著下调。本项目将以斑马鱼为材料，并采用基因芯片技术筛选出重离子辐射引起差异表达的Wnt信号通路相关基因，深入研究Wnt信号通路在重离子引起斑马鱼视觉损伤中的调控机制。

随着航空事业的发展，空间辐射对宇航员健康的影响受到越来越多的关注，而其中重离子辐射对于宇航员视觉神经影响最为显著。已有研究表明低LET的电离辐射可以引起白内障、视网膜和视神经萎缩等多种眼部并发症，还可能影响胚胎视网膜分化导致小眼畸形。因此，为了降低太空飞行中重离子辐射对宇航员视觉系统造成的危害，开展重离子辐射诱导视觉损伤的相关研究非常必要。Wnt信号通路在眼部发育过程中，对视网膜、角膜和晶体发育调控都起重要作用。模式生物斑马鱼由于其独特的优势，已经广泛应用与视觉发育及疾病的相关研究。本项目通过研究碳离子和铁离子辐照对斑马鱼胚胎的发育损伤及其分子机理，发现重离子造成视觉系统损伤的分子机制可能与细胞凋亡、DNA损伤和线粒体ATP合成相关，通过转录组测序分析表明重离子辐射对Wnt信号通路具有抑制作用，通过荧光定量PCR验证筛选出多个可能与重离子诱导的辐射损伤相关的Wnt信号通路关键基因。然后通过Wnt信号通路激活剂HLY78和抑制剂XAV939正向和反向调节Wnt信号通路，发现激活Wnt信号通路可缓解重离子诱导的包括视觉损伤在内的多种辐射损伤，而抑制Wnt信号通路则可以增加细胞对重离子的辐射敏感性，加剧重离子诱导的辐射损伤，说明了Wnt信号通路在重离子诱导斑马鱼视觉系统辐射损伤中的重要调控作用。本项目有助于了解太空飞行中重离子辐射对宇航员视觉系统造成潜在损伤的分子机理，为探索辐射防护机制和辐射防护药物的研发，进一步降低太空飞行中重离子辐射对宇航员造成的潜在危害提供了一定的理论基础。