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Posterior subcapsular cataracts are a late effect after acute exposure to 0.5 Gy ionizing radiation in mice

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posted on 2021-03-01, 16:00 authored by Sarah Kunze, Alexander Cecil, Cornelia Prehn, Gabriele Möller, Andreas Ohlmann, Gerhild Wildner, Stephan Thurau, Kristian Unger, Ute Rößler, Sabine M. Hölter, Soile Tapio, Florian Wagner, Andreas Beyerlein, Fabian Theis, Horst Zitzelsberger, Ulrike Kulka, Jerzy Adamski, Jochen Graw, Claudia Dalke

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 (60Co 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 Ercc2 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.

Funding

The work was supported by the German Federal Ministry of Education and Research [02NUK045A, B, C]. and at least in part by the LDLensRad consortium that has received funding from the Euratom research and training programme 2014-2018 in the framework of CONCERT [grant agreement No 662287].

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