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Cataractogenic load – a concept to study the contribution of ionizing radiation to accelerated aging in the eye lens

Uwineza, Alice; Kalligeraki, Alexia A.; Hamada, Nobuyuki; Jarrin, Miguel; Quinlan, Roy A.

Cataractogenic load – a concept to study the contribution of ionizing radiation to accelerated aging in the eye lens Thumbnail


Authors

Alice Uwineza

Alexia A. Kalligeraki

Nobuyuki Hamada

Miguel Jarrin



Abstract

Ionizing radiation (IR) damages DNA and other macromolecules, including proteins and lipids. Most cell types can repair DNA damage and cycle continuously their macromolecules as a mechanism to remove defective proteins and lipids. In those cells that lack nuclei and other organelles, such as lens fiber cells and mammalian erythrocytes, IR-induced damage to macromolecules is retained because they cannot be easily replenished. Whilst the life span for an erythrocyte is several months, the life span of a human lens is decades. There is very limited turnover in lens macromolecules, therefore the aging process greatly impacts lens structure and function over its lifetime. The lens is a tissue where biomolecular longevity, lifelong retention of its components and continued growth are integral to its homeostasis. These characteristics make the lens an excellent model to study the contribution of retained macromolecular damage over time. Epidemiological data have revealed a significant association between exposure to IR, the loss of lens optical function and the formation of cataracts (cataractogenesis) later in life. Lifestyle, genetic and environmental factors all contribute to cataractogenesis due to their effect on the aging process. Cataract is an iconic age-related disease in humans. IR is a recognised cause of cataract and the occupational lens dose limit is reduced from 150 to 20 mGy / year averaged over 5 years (ICRP Publication 118). Understanding the effects of low dose IR on the lens and its role in cataractogenesis is therefore very important. So we redefine “cataractogenic load” as a term to account for the combined lifestyle, genetic and environmental processes that increase biomolecular damage to lens macromolecules. These processes weaken metabolic defenses, increase post-translational protein modifications, and alter the lipid structure and content of the lens. IR exposure is a significant insult to the lens because of free radical generation and the ensuing oxidative stress. We support the concept that damage caused by IR compounds the aging process by increasing the cataractogenic load, hereby accelerating lens aging and its loss of function.

Citation

Uwineza, A., Kalligeraki, A. A., Hamada, N., Jarrin, M., & Quinlan, R. A. (2019). Cataractogenic load – a concept to study the contribution of ionizing radiation to accelerated aging in the eye lens. Mutation Research/Reviews in Mutation Research, 779, 68-81. https://doi.org/10.1016/j.mrrev.2019.02.004

Journal Article Type Article
Acceptance Date Feb 14, 2019
Online Publication Date Feb 15, 2019
Publication Date Jan 31, 2019
Deposit Date Feb 18, 2019
Publicly Available Date Mar 28, 2024
Journal Mutation Research - Reviews
Print ISSN 1383-5742
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 779
Pages 68-81
DOI https://doi.org/10.1016/j.mrrev.2019.02.004

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