Title: Sensitivity of the Lens Epithelium to Ionising Radiation
Funder: Department of Health (England)

Abstract: Background: The ICRP have recommended an occupational exposure limit of 1 Gy or 20 mSv/year averagaed over 5 years, to prevent radiation induced cataracts (ICRP Statement on Tissue Reactions, April 2011). These new low dose limits represent a significant reduction in previously recommended occupational exposure limits (0.5 Gy/year; ICRP Publication 85. Ann. ICRP 30 (2)). This could have serious implications, not least for medical practitioners. Yet experimental data based on the best animal and lens explant models to support such recommendations are not currently available for the low dose range ( Aims in relation to the issue to be addressed: 1. To pilot a mouse model to investigate the effects of low dose (0.1 - 2 Gy) ionising radiation on the eye lens so that non-invasive biodosimetry and exposure data on cataract risk can be obtained rapidly. 2. To determine the effects of low dose ionising radiation on the eye lens epithelium by quantifying cell metrics and numbers of proliferating and apoptotic cells in exposed samples. Research plan and methods of investigation: We will pilot a low-dose ionising radiation exposure model for lens opacities in the mouse. This is the preferred animal model because of the available genetic tools and resources to determine the mechanistic basis of the effects of ionising radiation. The Quinlan laboratory has extensively analysed the proliferation rates of animal and human lens epithelial cells using cell cycle biomarkers (Ki67, PCNA) and EdU labelling of newly synthesised DNA. The analyses also measured the shape, surface area and volume as well as the density of cells in the lens epithelia. Apoptosis was detected using TUNEL labelling. Using this knowledge base, the first signs of damage to the normal growth characteristics of lens epithelial cells by ionising radiation can be measured and quantified. Mice will be exposed to 0.1-2 Gy ionising radiation and their lens epithelia analysed at regular intervals over a 10 month period. In parallel, lens explants from human donors in their 5th decade will be exposed to a similar range of low dose ionising radiation and the effects similarly monitored. Research team: This is a collaborative project between Dr Elizabeth Ainsbury (Health Protection Agency) and Prof. Roy Quinlan (University of Durham). Both were invited participants in the EC Network of Excellence DoReMi workshop on radiation-induced lens opacities and as a result of that meeting and its recommendations this proposal has been prepared. Dr Ainsbury is a Principal Radiation Protection Scientist in the Cytogenetics and Biomarkers Group at the HPA Centre for Radiation, Chemical and Environmental Protection in Didcot. The Ainsbury research team is interdisciplinary and is charged with identifying new noninvasive biodosimetry markers of radiation damage. Roy Quinlan is Prof. of Biomedical Sciences with a 20 year pedigree of working on the cell biology of the eye lens. Potential impact/influence on the relevant policy field, users and wider stakeholders: This study will inform the debate on the recent ICRP recommendations regarding occupational exposure limits to prevent lens cataract. The bais for a rapid, non-invasive biodosimetry assay will be established so that cataract risk data can be gathered subsequently. Following steering group advice, our findings will be made available to both local (HPA; University of Durham) and international (DoReMi) groups and relevant radiation protection committees. Local groups also link with wider stakeholders such as health care professionals and the public. The Durham University and HPA websites both report research funding and highlight significant publications and results as part of their public outreach/services.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: EYE