Institute of Developmental Genetics, Helmholtz Zentrum München GmbH, German Research Center for Environmental Health, Neuherberg, Germany.
Research Unit Molecular Endocrinology and Metabolism, Genome Analysis Center, Helmholtz Center Munich German Research Center for Environmental Health, Neuherberg, Germany.
Int J Radiat Biol. 2021;97(4):529-540. doi: 10.1080/09553002.2021.1876951. Epub 2021 Mar 1.
The long-term effect of low and moderate doses of ionizing radiation on the lens is still a matter of debate and needs to be evaluated in more detail.
We conducted a detailed histological analysis of eyes from B6C3F1 mice cohorts after acute gamma irradiation (Co source; 0.063 Gy/min) at young adult age of 10 weeks with doses of 0.063, 0.125, and 0.5 Gy. Sham irradiated (0 Gy) mice were used as controls. To test for genetic susceptibility heterozygous mutant mice were used and compared to wild-type mice of the same strain background. Mice of both sexes were included in all cohorts. Eyes were collected 4 h, 12, 18 and 24 months after irradiation. For a better understanding of the underlying mechanisms, metabolomics analyses were performed in lenses and plasma samples of the same mouse cohorts at 4 and 12 h as well as 12, 18 and 24 months after irradiation. For this purpose, a targeted analysis was chosen.
This analysis revealed histological changes particularly in the posterior part of the lens that rarely can be observed by using Scheimpflug imaging, as we reported previously. We detected a significant increase of posterior subcapsular cataracts (PSCs) 18 and 24 months after irradiation with 0.5 Gy (odds ratio 9.3; 95% confidence interval 2.1-41.3) independent of sex and genotype. Doses below 0.5 Gy (i.e. 0.063 and 0.125 Gy) did not significantly increase the frequency of PSCs at any time point. In lenses, we observed a clear effect of sex and aging but not of irradiation or genotype. While metabolomics analyses of plasma from the same mice showed only a sex effect.
This article demonstrates a significant radiation-induced increase in the incidence of PSCs, which could not be identified using Scheimpflug imaging as the only diagnostic tool.
低剂量和中剂量电离辐射对晶状体的长期影响仍存在争议,需要更详细地评估。
我们对 B6C3F1 小鼠队列的眼睛进行了详细的组织学分析,这些小鼠在成年早期(10 周龄)接受急性γ辐射(Co 源;0.063Gy/min),剂量分别为 0.063、0.125 和 0.5Gy。接受假照射(0Gy)的小鼠作为对照。为了测试遗传易感性,我们使用杂合突变小鼠,并将其与同一品系背景的野生型小鼠进行比较。所有队列均包括雌雄小鼠。照射后 4h、12、18 和 24 个月收集眼睛。为了更好地了解潜在机制,我们还对同一批小鼠的晶状体和血浆样本进行了代谢组学分析,分别在照射后 4h、12h、18 和 24 个月进行了分析。为此,我们选择了靶向分析。
该分析显示,特别是在晶状体的后部分,存在组织学变化,这在以前我们的报告中,使用 Scheimpflug 成像很少能观察到。我们发现,在接受 0.5Gy 照射后 18 和 24 个月,后囊下白内障(PSCs)的发生率显著增加(优势比 9.3;95%置信区间 2.1-41.3),与性别和基因型无关。在任何时间点,低于 0.5Gy(即 0.063 和 0.125Gy)的剂量均不会显著增加 PSCs 的频率。在晶状体中,我们观察到性别和年龄的明显影响,但没有观察到照射或基因型的影响。虽然对来自同一批小鼠的血浆进行代谢组学分析仅显示出性别效应。
本文表明,使用 Scheimpflug 成像作为唯一的诊断工具,不能识别的 PSCs 的发生率显著增加与辐射有关。