Abstract

The lens of the eye is one of the most radiosensitive tissues. Although the exact mechanism of radiation-induced cataract development remains unknown, altered proliferation, migration, and adhesion have been proposed as factors. Lens epithelial cells were exposed to X-rays (0.1–2 Gy) and radiation effects were examined after 12 h and 7 day. Proliferation was quantified using an MTT assay, migration was measured using a Boyden chamber and wound-healing assay, and adhesion was assessed on three extracellular matrices. Transcriptional changes were also examined using RT-qPCR for a panel of genes related to these processes. In general, a nonlinear radiation response was observed, with the greatest effects occurring at a dose of 0.25 Gy. At this dose, a reduction in proliferation occurred 12 h post irradiation (82.06 ± 2.66%), followed by an increase at 7 day (116.16 ± 3.64%). Cell migration was increased at 0.25 Gy, with rates 121.66 ± 6.49% and 232.78 ± 22.22% greater than controls at 12 h and 7 day respectively. Cell adhesion was consistently reduced above doses of 0.25 Gy. Transcriptional alterations were identified at these same doses in multiple genes related to proliferation, migration, and adhesion. Overall, this research began to elucidate the functional changes that occur in lens cells following radiation exposure, thereby providing a better mechanistic understanding of radiation-induced cataract development.

Highlights

  • The lens of the eye has been said to be among the most radiosensitive tissues in the human body

  • We identified a significant decrease in expression of CDH2 (N-cadherin) at higher doses 7 days post irradiation, which correlated with our data showing a decrease in adhesion on all three extracellular matrices at these same doses and at this timepoint (Figure 4)

  • We demonstrated that 0.25 Gy irradiation resulted in a decrease in proliferation 12 h post irradiation, followed by an increase 7 days post irradiation

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Summary

Introduction

The lens of the eye has been said to be among the most radiosensitive tissues in the human body. The International Commission on Radiological Protection (ICRP) provides recommendations on occupational and public dose limits of ionizing radiation to various biological tissues including the lens of the eye. The most recent recommendations, published in 2012 in ICRP Publication 118, suggest that the threshold for cataract formation is even lower at an absorbed dose of 0.5 Gy from low linear energy transfer (LET) radiation [3]. The recommended equivalent dose limit to the eye was again lowered to 20 mSv per year, averaged over 5 years, with no single year exceeding 50 mSv [3]. These reductions in thresholds for radiation-induced cataracts have predominantly been the result of recent epidemiological studies

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