Abstract
Cataracts have long been known, but a biomathematical model is still unavailable for cataratogenesis. There has been a renewed interest in ionizing radiation cataracts because the recent international recommendation of the reduced lens dose limit stimulated the discussion toward its regulatory implementation in various countries. Nevertheless, a relationship between radiation (dose and dose rate) and response (e.g., incidence, onset and progression) remains incompletely understood, raising the need for a risk-predictive mathematical model. We here report for the first time an in silico model for cataractogenesis. First, a simplified cell proliferation model was developed for human lens growth based on stem and progenitor cell proliferation as well as epithelial-fiber cell differentiation. Then, a model for spontaneous cataractogenesis was developed to reproduce the human data on a relationship between age and cataract incidence. Finally, a model for radiation cataractogenesis was developed that can reproduce the human data on a relationship between dose and cataract onset at various ages, which was further applied to estimate cataract incidence following chronic lifetime exposure. The model can serve as the foundation for further development of the risk-predictive model for cataractogenesis along with additional considerations of various biological mechanisms and epidemiological datasets.
Highlights
A millennium has passed since the term “cataract” was coined [1]
With a set of parameter values determined to reproduce the Beaver Dam Eye Study (BDES) data and the Merriam and Focht data, our model was applied to estimate the incidence of posterior subcapsular (PSC) and cortical cataracts following chronic lifetime exposure where exposures occur at a constant dose rate from birth to age 80 years
This study is the first to report an in silico model for cataractogenesis
Summary
A millennium has passed since the term “cataract” was coined [1]. A cataract is a clouding or opacity of the normally transparent lens of the eye, and is the leading cause of visual impairment and blindness worldwide [2]. These results demonstrate that our model can reproduce the BDES data. With a set of parameter values determined to reproduce the BDES data and the Merriam and Focht data, our model was applied to estimate the incidence of PSC and cortical cataracts following chronic lifetime exposure where exposures occur at a constant dose rate from birth to age 80 years. (Fig 6D), and such an increase in cataract incidence at age 80 years was observed at a lifetime cumulative dose of 2 Gy (25 mGy/year) (S7 Fig)
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