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Accelerated loss of hearing and vision in the DNA-repair deficient Ercc1(δ/-) mouse
Marcella Spoor1, A Paul Nagtegaal, Yanto Ridwan
1Department of Neuroscience, Erasmus MC, Dr. Molewaterplein 50, 3015 GE Rotterdam, The Netherlands.
Abstract:
Age-related loss of hearing and vision are two very common disabling conditions, but the underlying mechanisms are still poorly understood. Damage by reactive oxygen species and other reactive cellular metabolites, which in turn may damage macromolecules such as DNA, has been implicated in both processes. To investigate whether DNA damage can contribute to age-related hearing and vision loss, we investigated hearing and vision in Ercc1(δ/-) mutant mice, which are deficient in DNA repair of helix-distorting DNA lesions and interstrand DNA crosslinks. Ercc1(δ/-) mice showed a progressive, accelerated increase of hearing level thresholds over time, most likely arising from deteriorating cochlear function. Ercc1(δ/-) mutants also displayed a progressive decrease in contrast sensitivity followed by thinning of the outer nuclear layer of the eyeball. The strong parallels with normal ageing suggest that unrepaired DNA damage can induce age-related decline of the auditory and visual system.
Insights
Unrepaired DNA damage accelerates age-related hearing and vision loss. Studies in mutant mice show impaired DNA repair leads to faster sensory system decline, suggesting a link between DNA integrity and aging.
Area of Science:
- Genetics
- Molecular Biology
- Ophthalmology
- Audiology
Background:
- Age-related hearing and vision loss are common but poorly understood. Reactive oxygen species and cellular damage are implicated. DNA damage is a potential contributor to these age-related sensory declines.
Purpose of the Study:
- To investigate the role of DNA damage in age-related hearing and vision loss.
- To examine hearing and vision in mice with impaired DNA repair mechanisms.
Main Methods:
- Utilized Ercc1(δ/-) mutant mice, which have deficiencies in repairing helix-distorting DNA lesions and interstrand DNA crosslinks.
- Assessed hearing thresholds and cochlear function over time.
- Evaluated visual function, including contrast sensitivity and retinal structure.
Main Results:
- Ercc1(δ/-) mice exhibited a progressive and accelerated increase in hearing thresholds, indicative of deteriorating cochlear function.
- Mutant mice showed a progressive decline in contrast sensitivity.
- Thinning of the outer nuclear layer of the eyeball was observed in Ercc1(δ/-) mutants.
Conclusions:
- Unrepaired DNA damage significantly contributes to the age-related decline of auditory and visual systems.
- The findings in Ercc1(δ/-) mice strongly parallel age-related changes observed in normal aging.
- Maintaining DNA repair capacity may be crucial for preserving sensory function during aging.
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