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Low dose space radiation-induced effects on the mouse retina and blood-retinal barrier integrity
Acta Astronautica ( IF 3.5 ) Pub Date : 2022-07-30 , DOI: 10.1016/j.actaastro.2022.07.029
Xiao Wen Mao , Seta Stanbouly , Bella Chieu , Vijayalakshmi Sridharan , Antiño R. Allen , Marjan Boerma

The health risk of flight condition-triggered ocular injury and neurodegeneration has long been a concern. Spaceflight missions will likely expose the astronauts and experiment payloads to greater radiation levels compared to those encountered on the Earth. Knowledge about the susceptibility to adverse effects from low doses of radiation during space missions is very limited. Our present study aims to investigate and compare the effects of whole-body simulated galactic cosmic rays (GCR) on blood-retinal barrier (BRB) integrity, oxidative stress, and apoptosis in the retina of male and female mouse models. Six-month-old male and female CD1 mice were either sham irradiated or received whole-body 5-ion simulated GCR exposure at a dose of 0.5 Gy. At four months following irradiation, mice were euthanized and ocular tissues were collected for histochemical analysis. BRB integrity was evaluated with biomarkers aquaporin-4 (AQP-4), a water channel protein, tight junction (TJ) Zonula occludens-1 (ZO-1), and adhesive molecule, platelet endothelial cell adhesion molecule-1 (PECAM-1). A significantly increased expression of AQP-4 was observed in the retina following GCR exposure compared to controls (p < 0.05) with more pronounced changes observed in the female mice over males. There was also a significant increase in the expression of PECAM-1 and a decrease in the expression of ZO-1 in the retina of irradiated groups compared to controls. Immunochemical analysis revealed enhanced immunoreactivity for oxidative biomarker, 4-hydroxynonenal (4-HNE) in the retina following radiation exposure. Significant increases in the numbers of apoptotic cells were also documented in the retina of irradiated male and female mice compared to controls (p < 0.05). Our study revealed that exposure to low-dose ionizing radiation induced cellular oxidative damage that may alter retina structure and BRB integrity. The results also demonstrate some sex-related differences in the radiation response. Further studies are needed to investigate the factors that contribute to gender- or genetic related variabilities in ocular changes to radiation exposure for a better understanding of the mechanisms of spaceflight-induced ocular findings.



中文翻译:

低剂量空间辐射对小鼠视网膜和血视网膜屏障完整性的影响

飞行条件引发的眼部损伤和神经退行性变的健康风险长期以来一直是一个问题。与地球上遇到的相比,太空飞行任务可能会使宇航员和实验有效载荷暴露在更大的辐射水平下。关于太空任务期间低剂量辐射对不利影响的敏感性的知识非常有限。我们目前的研究旨在调查和比较全身模拟银河宇宙射线 (GCR) 对雄性和雌性小鼠模型视网膜血视网膜屏障 (BRB) 完整性、氧化应激和细胞凋亡的影响。六个月大的雄性和雌性 CD1 小鼠要么接受假照射,要么接受 0.5 Gy 剂量的全身 5 离子模拟 GCR 暴露。照射后四个月,将小鼠安乐死并收集眼组织用于组织化学分析。使用生物标志物 aquaporin-4 (AQP-4)、水通道蛋白、紧密连接 (TJ) Zonula occludens-1 (ZO-1) 和粘附分子、血小板内皮细胞粘附分子-1 (PECAM-1) 评估 BRB 完整性)。与对照组相比 (p < 0.05),在 GCR 暴露后,在视网膜中观察到 AQP-4 的表达显着增加,在雌性小鼠中观察到比雄性小鼠更明显的变化。与对照组相比,照射组视网膜中 PECAM-1 的表达也显着增加,ZO-1 的表达降低。免疫化学分析显示,辐射暴露后视网膜中氧化性生物标志物 4-羟基壬烯醛 (4-HNE) 的免疫反应性增强。与对照组相比,受照射的雄性和雌性小鼠的视网膜中凋亡细胞数量也显着增加(p < 0.05)。我们的研究表明,暴露于低剂量电离辐射会引起细胞氧化损伤,这可能会改变视网膜结构和 BRB 完整性。结果还表明辐射反应存在一些与性别相关的差异。需要进一步研究以调查导致辐射暴露的眼部变化中与性别或遗传相关的变异的因素,以便更好地了解太空飞行引起的眼部发现的机制。我们的研究表明,暴露于低剂量电离辐射会引起细胞氧化损伤,这可能会改变视网膜结构和 BRB 完整性。结果还表明辐射反应存在一些与性别相关的差异。需要进一步研究以调查导致辐射暴露的眼部变化中与性别或遗传相关的变异的因素,以便更好地了解太空飞行引起的眼部发现的机制。我们的研究表明,暴露于低剂量电离辐射会引起细胞氧化损伤,这可能会改变视网膜结构和 BRB 完整性。结果还表明辐射反应存在一些与性别相关的差异。需要进一步的研究来调查导致辐射暴露的眼部变化中与性别或遗传相关的变异的因素,以便更好地了解太空飞行引起的眼部发现的机制。

更新日期:2022-08-02
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