Radiation-Induced Lens Opacity and Cataractogenesis: A Lifetime Study Using Mice of Varying Genetic Backgrounds

R. A. McCarron; S. G.R. Barnard; G. Babini; C. Dalke; J. Graw; S. Leonardi; M. Mancuso; J. E. Moquet; D. Pawliczek; S. Pazzaglia; I. De Stefano; E. A. Ainsbury

doi:10.1667/RADE-20-00266.1

Radiation-Induced Lens Opacity and Cataractogenesis: A Lifetime Study Using Mice of Varying Genetic Backgrounds

R. A. McCarron, S. G.R. Barnard, G. Babini, C. Dalke, J. Graw, S. Leonardi, M. Mancuso, J. E. Moquet, D. Pawliczek, S. Pazzaglia, I. De Stefano, E. A. Ainsbury

Radiation Effects

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9 Citations (Scopus)

Abstract

Recent epidemiological findings and reanalysis of historical data suggest lens opacities resulting from ionizing radiation exposures are likely induced at lower doses than previously thought. These observations have led to ICRP recommendations for a reduction in the occupational dose limits for the eye lens, as well as subsequent implementation in EU member states. The EU CONCERT LDLensRad project was initiated to further understand the effects of ionizing radiation on the lens and identify the mechanism(s) involved in radiation-induced cataract, as well as the impact of dose and dose-rate. Here, we present the results of a long-term study of changes to lens opacity in male and female adult mice from a variety of different genetic (radiosensitive or radioresistant) backgrounds, including mutant strains Ercc2 and Ptch1, which were assumed to be susceptible to radiation-induced lens opacities. Mice received 0.5, 1 and 2 Gy Co-60 gamma-ray irradiation at dose rates of 0.063 and 0.3 Gy min(-1). Scheimpflug imaging was used to quantify lens opacification as an early indicator of cataract, with monthly observations taken postirradiation for an 18-month period in all strains apart from 129S2, which were observed for 12 months. Opacification of the lens was found to increase with time postirradiation (with age) for most mouse models, with ionizing radiation exposure increasing opacities further. Sex, dose, dose rate and genetic background were all found to be significant contributors to opacification; however, significant interactions were identified, which meant that the impact of these factors was strain dependent. Mean lens density increased with higher dose and dose rate in the presence of Ercc2 and Ptch1 mutations. This project was the first to focus on low (

Original language	English
Pages (from-to)	57-66
Number of pages	10
Journal	Radiation Research
Volume	197
Issue number	1
Early online date	13 May 2021
DOIs	https://doi.org/10.1667/RADE-20-00266.1
Publication status	Published - 1 Jan 2022

Bibliographical note

Funding Information: We thank all the wider partners and Advisory Board members of the LDLensRad project. This was very much a team effort, and a great
pleasure; LDLensRad (the European CONCERT project starting in 2017): Towards a full mechanistic understanding of low dose radiation-induced cataracts (https://bit.ly/3mRaT7p). We also thank the wider CONCERT consortium partners, in addition to Mark Hill and James Thompson from the Oxford Institute for Radiation Oncology, and Bob Sokolowski of MRC Harwell for support with the irradiation facility. The LDLensRad project has received funding from the Euratom Research And Training Programme 2014–2018 in the framework of the CONCERT (grant agreement no. 662287). This publication reflects only the authors’ views.
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.

Open Access: Free to read, but no Open Access licence.

Publisher Copyright: ©2022 by Radiation Research Society. All rights of reproduction in any form reserved.

Citation: R. A. McCarron, S. G. R. Barnard, G. Babini, C. Dalke, J. Graw, S. Leonardi, M. Mancuso, J. E. Moquet, D. Pawliczek, S. Pazzaglia, I. De Stefano, E. A. Ainsbury, for the LDLensRad Consortium "Radiation-Induced Lens Opacity and Cataractogenesis: A Lifetime Study Using Mice of Varying Genetic Backgrounds," Radiation Research, 197(1), 57-66, (13 May 2021)

DOI: https://doi.org/10.1667/RADE-20-00266.1

Keywords

AGE
ESTROGEN
GENDER
INDUCED CATARACTS
IONIZING-RADIATION
PROTECTS
REPAIR

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10.1667/RADE-20-00266.1

Cite this

McCarron, R. A., Barnard, S. G. R., Babini, G., Dalke, C., Graw, J., Leonardi, S., Mancuso, M., Moquet, J. E., Pawliczek, D., Pazzaglia, S., De Stefano, I., & Ainsbury, E. A. (2022). Radiation-Induced Lens Opacity and Cataractogenesis: A Lifetime Study Using Mice of Varying Genetic Backgrounds. Radiation Research, 197(1), 57-66. https://doi.org/10.1667/RADE-20-00266.1

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abstract = "Recent epidemiological findings and reanalysis of historical data suggest lens opacities resulting from ionizing radiation exposures are likely induced at lower doses than previously thought. These observations have led to ICRP recommendations for a reduction in the occupational dose limits for the eye lens, as well as subsequent implementation in EU member states. The EU CONCERT LDLensRad project was initiated to further understand the effects of ionizing radiation on the lens and identify the mechanism(s) involved in radiation-induced cataract, as well as the impact of dose and dose-rate. Here, we present the results of a long-term study of changes to lens opacity in male and female adult mice from a variety of different genetic (radiosensitive or radioresistant) backgrounds, including mutant strains Ercc2 and Ptch1, which were assumed to be susceptible to radiation-induced lens opacities. Mice received 0.5, 1 and 2 Gy Co-60 gamma-ray irradiation at dose rates of 0.063 and 0.3 Gy min(-1). Scheimpflug imaging was used to quantify lens opacification as an early indicator of cataract, with monthly observations taken postirradiation for an 18-month period in all strains apart from 129S2, which were observed for 12 months. Opacification of the lens was found to increase with time postirradiation (with age) for most mouse models, with ionizing radiation exposure increasing opacities further. Sex, dose, dose rate and genetic background were all found to be significant contributors to opacification; however, significant interactions were identified, which meant that the impact of these factors was strain dependent. Mean lens density increased with higher dose and dose rate in the presence of Ercc2 and Ptch1 mutations. This project was the first to focus on low (",

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author = "McCarron, {R. A.} and Barnard, {S. G.R.} and G. Babini and C. Dalke and J. Graw and S. Leonardi and M. Mancuso and Moquet, {J. E.} and D. Pawliczek and S. Pazzaglia and {De Stefano}, I. and Ainsbury, {E. A.}",

note = "Funding Information: We thank all the wider partners and Advisory Board members of the LDLensRad project. This was very much a team effort, and a great pleasure; LDLensRad (the European CONCERT project starting in 2017): Towards a full mechanistic understanding of low dose radiation-induced cataracts (https://bit.ly/3mRaT7p). We also thank the wider CONCERT consortium partners, in addition to Mark Hill and James Thompson from the Oxford Institute for Radiation Oncology, and Bob Sokolowski of MRC Harwell for support with the irradiation facility. The LDLensRad project has received funding from the Euratom Research And Training Programme 2014–2018 in the framework of the CONCERT (grant agreement no. 662287). This publication reflects only the authors{\textquoteright} views. 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. Open Access: Free to read, but no Open Access licence. Publisher Copyright: {\textcopyright}2022 by Radiation Research Society. All rights of reproduction in any form reserved. Citation: R. A. McCarron, S. G. R. Barnard, G. Babini, C. Dalke, J. Graw, S. Leonardi, M. Mancuso, J. E. Moquet, D. Pawliczek, S. Pazzaglia, I. De Stefano, E. A. Ainsbury, for the LDLensRad Consortium {"}Radiation-Induced Lens Opacity and Cataractogenesis: A Lifetime Study Using Mice of Varying Genetic Backgrounds,{"} Radiation Research, 197(1), 57-66, (13 May 2021) DOI: https://doi.org/10.1667/RADE-20-00266.1",

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N1 - Funding Information: We thank all the wider partners and Advisory Board members of the LDLensRad project. This was very much a team effort, and a great pleasure; LDLensRad (the European CONCERT project starting in 2017): Towards a full mechanistic understanding of low dose radiation-induced cataracts (https://bit.ly/3mRaT7p). We also thank the wider CONCERT consortium partners, in addition to Mark Hill and James Thompson from the Oxford Institute for Radiation Oncology, and Bob Sokolowski of MRC Harwell for support with the irradiation facility. The LDLensRad project has received funding from the Euratom Research And Training Programme 2014–2018 in the framework of the CONCERT (grant agreement no. 662287). This publication reflects only the authors’ views. 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. Open Access: Free to read, but no Open Access licence. Publisher Copyright: ©2022 by Radiation Research Society. All rights of reproduction in any form reserved. Citation: R. A. McCarron, S. G. R. Barnard, G. Babini, C. Dalke, J. Graw, S. Leonardi, M. Mancuso, J. E. Moquet, D. Pawliczek, S. Pazzaglia, I. De Stefano, E. A. Ainsbury, for the LDLensRad Consortium "Radiation-Induced Lens Opacity and Cataractogenesis: A Lifetime Study Using Mice of Varying Genetic Backgrounds," Radiation Research, 197(1), 57-66, (13 May 2021) DOI: https://doi.org/10.1667/RADE-20-00266.1

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Radiation-Induced Lens Opacity and Cataractogenesis: A Lifetime Study Using Mice of Varying Genetic Backgrounds

Abstract

Bibliographical note

Keywords

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