Abstract
Elevated cataract risk after radiation exposure was established soon after the discovery of X-rays in 1895. Today, increased cataract incidence among medical imaging practitioners and after nuclear incidents has highlighted how little is still understood about the biological responses of the lens to low-dose ionizing radiation (IR). Here, we show for the first time that in mice, lens epithelial cells (LECs) in the peripheral region repair DNA double strand breaks (DSB) after exposure to 20 and 100 mGy more slowly compared with circulating blood lymphocytes, as demonstrated by counts of γH2AX foci in cell nuclei. LECs in the central region repaired DSBs faster than either LECs in the lens periphery or lymphocytes. Although DSB markers (γH2AX, 53BP1 and RAD51) in both lens regions showed linear dose responses at the 1 h timepoint, nonlinear responses were observed in lenses for EdU (5-ethynyl-2′-deoxy-uridine) incorporation, cyclin D1 staining and cell density after 24 h at 100 and 250 mGy. After 10 months, the lens aspect ratio was also altered, an indicator of the consequences of the altered cell proliferation and cell density changes. A best-fit model demonstrated a dose-response peak at 500 mGy. These data identify specific nonlinear biological responses to low (less than 1000 mGy) dose IR-induced DNA damage in the lens epithelium.
Highlights
Vision is one of the most important senses to animals, which has evolved successfully to allow spatial definition [1]
We show for the first time that in mice, lens epithelial cells (LECs) in the peripheral region repair DNA double strand breaks (DSB) after exposure to 20 and 100 mGy more slowly compared with circulating blood lymphocytes, as demonstrated by counts of gH2AX foci in cell nuclei
DSB markers in both lens regions showed linear dose responses at the 1 h timepoint, nonlinear responses were observed in lenses for EdU (5-ethynyl-20-deoxy-uridine) incorporation, cyclin D1 staining and cell density after 24 h at 100 and 250 mGy
Summary
Vision is one of the most important senses to animals, which has evolved successfully to allow spatial definition [1]. Lens epithelial cells (LECs) differentiate into fibre cells in this ‘peripheral’ region of the epithelium, entering the body of the lens via the meridional rows (MR) in the TZ [6], where the timely, organized formation of fibre cells is regulated by, for instance, aPKCl [7] and src/ephrin A2 [8]. Such proteins ensure the maintenance of the geometric organization of the fibre cells, which is so important to lens function [3,9].
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