The effect(s) of dose and dose-rate of ionising radiation on early lens epithelial cell response and cataractogenesis

Abstract

The lens of the eye is thought to be one of the most radiosensitive tissues. Cataracts were one of the first observed biological effects following ionising radiation exposure. The recent change in regulations for eye lens dose limits has led to the urgent need to make sure our biological understanding is sufficient. The anterior of the lens is covered by lens epithelial cells (LEC), that are critical to maintaining normal lens function and producing fibre cells. Damage or disruption to LECs can have detrimental consequences to the lens. Low dose (<500 mGy) radiation-induced DNA damage and repair, cell proliferation and lens opacity were investigated post-exposure in or amongst four mouse strains (C57BL/6,129S2, BALB/c and CBA/Ca). Mice were sacrificed up to 24 hours post-exposure and lenses removed and epithelia isolated for analyses. Immunofluorescent staining for DNA double strand break (DSB) repair (53BP1) and cell proliferation (Ki67) were performed. Dose, dose-rates were varied during exposures to seek experimental evidence to support the epidemiological studies. Peripheral blood lymphocytes were collected for comparison with LEC. 120 female mice were irradiated and their lenses analysed for opacity at monthly intervals over 18 months. An inverse dose-rate effect was observed in the DSB repair response, as well as slower repair at low IR doses and a significant strain dependency. A nonlinear response to IR was observed for LEC proliferation that was bimodal; inhibition at low dose (<50 mGy), and a significant interaction effect between dose-rate and region. Lens opacity also increased over time. These results give the first biological evidence for an inverse dose-rate response in the lens. They highlight the importance of dose-rate in low-dose cataract formation represent the first evidence that LECs process radiation damage differently to blood lymphocytes. More work is needed to support lens dose limits.