https://orcid.org/0000-0002-6575-1097
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Abstract
Purpose
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.
Material and Methods
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.
Results
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.
Conclusions
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.
Acknowledgments
The authors thank Silke Becker, Erika Bürkle, Monika Stadler and Andreas Schirmer for expert technical assistance. We would like to thank all partners of the INSTRA project. 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]. This publication reflects only the authors' view. Responsibility for the information and views expressed therein lies entirely with the authors. The European Commission is not responsible for any use that may be made of the information it contains.
Disclosure statement
The authors declare no conflict of interest.
Additional information
Funding
Notes on contributors
Sarah Kunze
Sarah Kunze was a PhD student in the Institute of Developmental Genetics at the Helmholtz Zentrum München. Now she is lab coordinator at the University Eye Clinic in Bonn in Prof. Busskamp’s group.
Alexander Cecil
Alexander Cecil is scientist in the Research Unit Molecular Endocrinology and Metabolism at the Helmholtz Zentrum München.
Cornelia Prehn
Cornelia Prehn is senior scientist in the Research Unit Molecular Endocrinology and Metabolism at the Helmholtz Zentrum München.
Gabriele Möller
Gabriele Möller is senior scientist in the Research Unit Molecular Endocrinology and Metabolism at the Helmholtz Zentrum München.
Andreas Ohlmann
Andreas Ohlmann is head of the Laboratory for Molecular and Cell Biology at the Department of Ophthalmology of the Ludwig-Maximilians-University Munich.
Gerhild Wildner
Gerhild Wildner holds a diploma in Biology/Genetics/Immunology from the University of Cologne, Germany, a PhD in Human genetics/Immunology of the LMU Munich, is a professor of immunology, certified immunologist and head of the Section of Immunobiology at the Dept. of Ophthalmology, University Hospital LMU Munich, Germany.
Stephan Thurau
Stephan Thurau has studied medicine in Kiel and Munich and holds an MD in immunology. He is a FEBO, professor of ophthalmology and assistant medical director of the uveitis clinic at the Dept. of Ophthalmology, University Hospital LMU Munich, Germany.
Kristian Unger
Kristian Unger is Head of Integrative Biology Group and Deputy Head of Research Unit Radiation Cytogenetics at Helmholtz Zentrum München.
Ute Rößler
Ute Rößler, PhD, biologist, working on topics of radiation effects and radiation sensitivity as a senior scientist at the Federal Office for Radiation Protection.
Sabine M. Hölter
Sabine M. Hölter is group leader of the Behavioral Neuroscience team in the Institute of Developmental Genetics at the Helmholtz Zentrum München.
Soile Tapio
Soile Tapio, PhD, leads the group of Radiation Proteomics at the Institute of Radiation Biology at Helmholtz Zentrum München. Her research topic is radiation-induced normal tissue damage.
Florian Wagner
Florian Wagner is Technical Assistant in the Radiation Facilities at Helmholtz Zentrum München.
Andreas Beyerlein
Andreas Beyerlein was scientist in the Institute of Computational Biology at Helmholtz Zentrum München.
Fabian Theis
Fabian Theis is Director of Institute of Computational Biology at Helmholtz Zentrum München.
Horst Zitzelsberger
Horst Zitzelsberger is Head of Research Unit Radiation Cytogenetics and Group Leader of Radiocarcinogenesis Group at Helmholtz Zentrum München.
Ulrike Kulka
Ulrike Kulka is head of unit national and international cooperation and reporting at the Federal Office for Radiation Protection in Oberschleißheim, Germany.
Jerzy Adamski
Jerzy Adamski acts as Head of Genome Analysis Center and is director of Research Unit Molecular Endocrinology and Metabolism at Helmholtz Zentrum München.
Jochen Graw
Jochen Graw was head of the Research Group Eye Diseases in the Institute of Developmental Genetics at the Helmholtz Zentrum München. He is retired now.
Claudia Dalke
Claudia Dalke is a research scientist and study coordinator at Helmholtz Zentrum München.
