IAS Fellow's Seminar - Radiation cataract: A model system for studying the effects of low dose ionizing radiation exposure and genetic determinants of radiosensitivity
The lens is considered one of the most radiosensitive tissues in the body and the primary pathology associated with ionizing radiation exposure, cataract, or loss of transparency of the lens, is easily observed in-vivo. Thus, the lens provides a unique model system in which to study the effects of low dose ionizing radiation exposure in a complex, highly organized tissue.
Considerable uncertainties, however, surround the relationship between dose and cataract development. Current national and international ocular-radiation protection guidelines, based on decades earlier studies of radiation cataract, are predicated on the view that cataractogenesis is a deterministic event and requires a relatively high threshold radiation dose before visually disabling lens opacities develop. Such studies generally had short follow-up periods, failed to take into account increasing latency as dose decreased, did not have sufficient sensitivity to detect early lens changes and had relatively few subjects with doses below a few Gy. Newer data from animal models and from exposed human populations are consistent with a small or even zero dose threshold. For example, in populations exposed to far lower doses of radiation, including those undergoing CAT scans, radiotherapy, the astronaut pool, atomic bomb survivors, residents of radioactively contaminated buildings, interventional physicians and medical workers and the Chernobyl accident “Liquidators”, dose-related lens opacification at significantly lower exposures was reported. The concept of a dose threshold is critical not only to risk assessment but also to theories regarding the mechanism(s) of radiation cataract.
At the same time, recent epidemiological studies suggest the existence of radiosensitive human sub-populations, which further complicates assessment of a putative threshold radiation cataract dose. It has been suggested that individuals haplo-insufficient for one or more genes involved in DNA damage repair and/or cell cycle checkpoint control may be especially susceptible to the cataractogenic effects of ionizing radiation. If this hypothesis were true, it would be unethical to put radiosensitive individuals in situations where they might receive relatively high doses. At the same time, inclusion of such individuals in epidemiological studies may distort the shape of the dose-response curve such that a linear extrapolation from high to low doses may be invalid. These observations have clear implications for radiotherapy, diagnostic procedures and for those occupationally exposed to ionizing radiation, such as interventional medical personnel or the astronaut core and may aid in determining future national terrestrial and space radiation risk policies.
Fellows' seminars take place on Monday lunchtimes in the seminar room at Cosin's Hall.
Places are limited and so any academic colleagues interested in attending a seminar should contact the Institute in advance to reserve a place.
The aim of these seminars is to develop new thinking on the big issues that are of current concern/interest for the Fellows . Each Fellow is asked to present a core idea that informs their current work, or a problem that they are tackling, that could benefit from cross-disciplinary thinking. These seminars are informal and designed to encourage discussion.
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