Seeing through a glass darkly and taking the next right steps

Dauer, Lawrence T.

doi:10.1007/s10654-018-0458-9

Cited by 6 publications

(4 citation statements)

References 17 publications

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“…57 Integration of epidemiology and biology has long been discussed for cancer. 58 This would also indeed be needed for cataracts, 59 and development of risk-predictive biomathematical models 60 would be important.…”

Section: Do Minor Opacities Progress Into Vision Impairing Cataracts?mentioning

confidence: 99%

An update on effects of ionizing radiation exposure on the eye

Hamada

Азизова

Little

2020

BJR

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The International Commission on Radiological Protection (ICRP) has considered for over 60 years that the lens of the eye is among the most radiosensitive tissues, and has recommended dose limits for the lens to prevent occurrence of vision impairing cataracts (VICs). Epidemiological evidence that doses much lower than previously thought produce cataracts led ICRP to recommend reducing dose threshold for VICs and reducing an occupational equivalent dose limit for the lens in 2011, when only a single threshold of 0.5 Gy was recommended. On the basis of epidemiological evidence, ICRP assumed progression of minor opacities into VICs and no dose rate effect. This contrasts with previously recommended separate thresholds for minor opacities and VICs, and for different exposure scenarios. Progression was assumed based on similar risks of cataracts and cataract surgery in Japanese atomic bomb survivors. The absence of dose rate effect derived from the observed similar thresholds for protracted exposures in Chernobyl cleanup workers and in atomic bomb survivors. Since 2011, there has been an increasing body of epidemiological evidence relating to cataracts and other ocular diseases (i.e. glaucoma and macular degeneration), particularly at low doses and low dose rates. This review paper gives an overview of the scientific basis of the 2011 ICRP recommendation, discusses the plausibility of these two assumptions in the light of emerging scientific evidence, and considers the radiosensitivity of the lens among ocular structures.

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Section: Do Minor Opacities Progress Into Vision Impairing Cataracts?mentioning

confidence: 99%

An update on effects of ionizing radiation exposure on the eye

Hamada

Азизова

Little

2020

BJR

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“…For cancer, integration of epidemiology and biology has long been discussed (246,247), and epidemiological data have been applied to several biologically based mechanistic models (248,249). The integrative approach would also indeed be needed for cataracts (250), DCS (247) and other noncancer effects, but such studies are very limited, e.g., for cataracts (251) and DCS (252)(253)(254)(255). To this end, developments of biologically based dose response (BBDR) models would be critical to enhance the risk assessment process (by reducing uncertainty in risk estimates at low dose and low dose rate), and developments of adverse outcome pathways (AOPs) would be required to determine BBDR model parameters (247).…”

Section: Integration Of Epidemiology and Biologymentioning

confidence: 99%

Noncancer Effects of Ionizing Radiation Exposure on the Eye, the Circulatory System and beyond: Developments made since the 2011 ICRP Statement on Tissue Reactions

Hamada

2023

Radiation Research

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For radiation protection purposes, noncancer effects with a threshold-type dose-response relationship have been classified as tissue reactions (formerly called nonstochastic or deterministic effects), and equivalent dose limits aim to prevent occurrence of such tissue reactions. Accumulating evidence demonstrates increased risks for several late occurring noncancer effects at doses and dose rates much lower than previously considered. In 2011, the International Commission on Radiological Protection (ICRP) issued a statement on tissue reactions to recommend a threshold of 0.5 Gy to the lens of the eye for cataracts and to the heart and brain for diseases of the circulatory system (DCS), independent of dose rate. Literature published thereafter continues to provide updated knowledge. Increased risks for cataracts below 0.5 Gy have been reported in several cohorts (e.g., including in those receiving protracted or chronic exposures). A dose threshold for cataracts is less evident with longer follow-up, with limited evidence available for risk of cataract removal surgery. There is emerging evidence for risk of normal-tension glaucoma and diabetic retinopathy, but the long-held tenet that the lens represents among the most radiosensitive tissues in the eye and in the body seems to remain unchanged. For DCS, increased risks have been reported in various cohorts, but the existence or otherwise of a dose threshold is unclear. The level of risk is less uncertain at lower dose and lower dose rate, with the possibility that risk per unit dose is greater at lower doses and dose rates. Target organs and tissues for DCS are also unknown, but may include heart, large blood vessels and kidneys. Identification of potential factors (e.g., sex, age, lifestyle factors, coexposures, comorbidities, genetics and epigenetics) that may modify radiation risk of cataracts and DCS would be important. Other noncancer effects on the radar include neurological effects (e.g., Parkinsonŉs disease and dementia) of which elevated risk has increasingly been reported. These late occurring noncancer effects tend to deviate from the definition of tissue reactions, necessitating more scientific developments to reconsider the radiation effect classification system and risk management. This paper gives an overview of historical developments made in ICRP prior to the 2011 statement and an update on relevant developments made since the 2011 ICRP statement.

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“…Both ICRP and NCRP have recently emphasized the need of a more mechanistically based model for radiation protection purposes [14,15]. Besides, the need of integrating biology and epidemiology for radiation cataracts has recently been highlighted [16]. However, mathematical modeling of the lens growth, spontaneous cataractogenesis and IR cataractogenesis has not been described in the literature, with a single exception of one report on cell-density distribution in the lens epithelium of animal lenses [17].…”

Section: Introductionmentioning

confidence: 99%

A biologically based mathematical model for spontaneous and ionizing radiation cataractogenesis

2019

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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.

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Seeing through a glass darkly and taking the next right steps

Cited by 6 publications

References 17 publications

An update on effects of ionizing radiation exposure on the eye

An update on effects of ionizing radiation exposure on the eye

Noncancer Effects of Ionizing Radiation Exposure on the Eye, the Circulatory System and beyond: Developments made since the 2011 ICRP Statement on Tissue Reactions

A biologically based mathematical model for spontaneous and ionizing radiation cataractogenesis

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