title: Ionizing radiation induced cataracts: Recent biological and mechanistic developments and perspectives for future research.
abstract: The lens of the eye has long been considered as a radiosensitive tissue, but recent research has suggested that the radiosensitivity is even greater than previously thought. The 2012 recommendation of the International Commission on Radiological Protection (ICRP) to substantially reduce the annual occupational equivalent dose limit for the ocular lens has now been adopted in the European Union and is under consideration around the rest of the world. However, ICRP clearly states that the recommendations are chiefly based on epidemiological evidence because there are a very small number of studies that provide explicit biological, mechanistic evidence at doses <2Gy. This paper aims to present a review of recently published information on the biological and mechanistic aspects of cataracts induced by exposure to ionizing radiation (IR). The data were compiled by assessing the pertinent literature in several distinct areas which contribute to the understanding of IR induced cataracts, information regarding lens biology and general processes of cataractogenesis. Results from cellular and tissue level studies and animal models, and relevant human studies, were examined. The main focus was the biological effects of low linear energy transfer IR, but dosimetry issues and a number of other confounding factors were also considered. The results of this review clearly highlight a number of gaps in current knowledge. Overall, while there have been a number of recent advances in understanding, it remains unknown exactly how IR exposure contributes to opacification. A fuller understanding of how exposure to relatively low doses of IR promotes induction and/or progression of IR-induced cataracts will have important implications for prevention and treatment of this disease, as well as for the field of radiation protection.
authors.affiliation: Public Health England Centre for Chemical, Radiological and Environmental Hazards, Chilton, Didcot, Oxford OX11 0RQ, UK. Electronic address: Liz.Ainsbury@phe.gov.uk.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Ainsbury
authors.affiliation: Public Health England Centre for Chemical, Radiological and Environmental Hazards, Chilton, Didcot, Oxford OX11 0RQ, UK. Electronic address: Stephen.Barnard@phe.gov.uk.
authors.forename: Stephen
authors.initials: S
authors.lastname: Barnard
authors.affiliation: Genomic Instability Group, Department of Biological and Medical Sciences, Oxford Brookes University, Gipsy Lane Campus, Headington, Oxford OX3 0BP, UK. Electronic address: SBright@brookes.ac.uk.
authors.forename: Scott
authors.initials: S
authors.lastname: Bright
authors.affiliation: Helmholtz Zentrum München GmbH, German Research Center for Environmental Health, Institute of Developmental Genetics, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany. Electronic address: dalke@helmholtz-muenchen.de.
authors.forename: Claudia
authors.initials: C
authors.lastname: Dalke
authors.affiliation: Biophysical Sciences Institute, University of Durham, Durham DH1 3LE, UK. Electronic address: miguel.jarrin@durham.ac.uk.
authors.forename: Miguel
authors.initials: M
authors.lastname: Jarrin
authors.affiliation: Helmholtz Zentrum München GmbH, German Research Center for Environmental Health, Institute of Developmental Genetics, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany. Electronic address: sarah.kunze@helmholtz-muenchen.de.
authors.forename: Sarah
authors.initials: S
authors.lastname: Kunze
authors.affiliation: Public Health England Centre for Chemical, Radiological and Environmental Hazards, Chilton, Didcot, Oxford OX11 0RQ, UK. Electronic address: Rick.Tanner@phe.gov.uk.
authors.forename: Rick
authors.initials: R
authors.lastname: Tanner
authors.affiliation: Indiana University School of Medicine, Department of Radiation Oncology, 535 Barnhill Drive, RT 041, Indianapolis, IN 46202-5289, USA. Electronic address: jdynlach@iupui.edu.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Dynlacht
authors.affiliation: Biophysical Sciences Institute, University of Durham, Durham DH1 3LE, UK. Electronic address: r.a.quinlan@durham.ac.uk.
authors.forename: Roy A
authors.initials: RA
authors.lastname: Quinlan
authors.affiliation: Helmholtz Zentrum München GmbH, German Research Center for Environmental Health, Institute of Developmental Genetics, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany. Electronic address: graw@helmholtz-muenchen.de.
authors.forename: Jochen
authors.initials: J
authors.lastname: Graw
authors.affiliation: Genomic Instability Group, Department of Biological and Medical Sciences, Oxford Brookes University, Gipsy Lane Campus, Headington, Oxford OX3 0BP, UK. Electronic address: MKadhim@brookes.ac.uk.
authors.forename: Munira
authors.initials: M
authors.lastname: Kadhim
authors.affiliation: Radiation Safety Research Center, Nuclear Technology Research Laboratory, Central Research Institute of Electric Power Industry (CRIEPI), 2-11-1 Iwado-kita, Komae, Tokyo 201-8511, Japan. Electronic address: hamada-n@criepi.denken.or.jp.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hamada
mesh_terms: D000818:Animals; D002386:Cataract / Q000209:etiology* / Q000473:pathology; D003318:Corneal Opacity / Q000209:etiology; D006801:Humans; D007908:Lens, Crystalline / Q000378:metabolism / Q000502:physiology / Q000528:radiation effects; D023421:Models, Animal; D011839:Radiation, Ionizing
keywords: Cataract mechanisms; Dosimetric modeling; IR; Lens biology; Radiation cataract; Radiation lens effects