Dataset Information

Age-Related Retinal Changes in Wild-Type C57BL/6J Mice Between 2 and 32 Months.

ABSTRACT:

Purpose

The purpose of this study was to extend our understanding of how aging affects normal retina function and morphology in wild-type C57BL/6J mice, by analyzing electrophysiological recordings and in vivo and post mortem anatomy.

Methods

Electroretinograms (ERGs), spectral domain optical coherence tomography (SD-OCT), and confocal scanning laser ophthalmoscope (cSLO) in vivo images were obtained from mice between the ages of 2 and 32 months in four groups: group 1 (<0.5 years), group 2 (1.0-1.5 years), group 3 (1.5-2.0 years), and group 4 (>2.0 years). Afterward, mouse bodies and eyes were weighed. Eyes were stained with hematoxylin and eosin (H&E) and cell nuclei were quantified.

Results

With aging, mice showed a significant reduction in both a- and b-wave ERG amplitudes in scotopic and photopic conditions. Additionally, total retina and outer nuclear layer (ONL) thickness, as measured by SD-OCT images, were significantly reduced in older groups. The cSLO images showed an increase in auto-fluorescence at the photoreceptor-RPE interface as age increases. H&E cell nuclei quantification showed significant reduction in the ONL in older ages, but no differences in the inner nuclear layer (INL) or ganglion cell layer (GCL).

Conclusions

By using multiple age groups and extending the upper age limit of our animals to approximately 2.65 years (P970), we found that natural aging causes negative effects on retinal function and morphology in a gradual, rather than abrupt, process. Future studies should investigate the exact mechanisms that contribute to these gradual declines in order to discover pathways that could potentially serve as therapeutic targets.

SUBMITTER: Ferdous S

PROVIDER: S-EPMC8196434 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Aim: Aging is thought to coincide with gradual and progressive changes in brain function and behavior over the lifetime. Our previous meta-analytic study reported age-related behavioral changes from young to middle age in male C57BL/6J mice. However, the previous study had some limitations that could affect the generalizability of the findings because of the potential influence of genetic and environmental factors on behavior, in addition to a lack of information regarding the behaviors of old-aged mice. Here, to investigate age-related behavioral changes from young to old age in mice, we analyzed the behaviors of male C57BL/6J mice from four different age groups (8, 47, 73, and 99 weeks of age at the beginning of the experiment) from a colony that had been maintained in a genetically controlled condition based on The Jackson Laboratory's Genetic Stability Program in an environmentally controlled animal facility.Methods: We used a battery of behavioral tests, including the light/dark transition, open field, elevated plus maze, hot plate, social interaction, rotarod, three-chamber social approach, prepulse inhibition, Porsolt forced swim, T-maze, Barnes maze, tail suspension, and fear-conditioning tests.Results: Some behavioral changes occurred between young and middle age, and further changes in various behaviors were observed in old age. Decreased locomotor activity and increased anxiety-like behavior were found in old-aged mice compared to those in young and middle-aged mice in the light/dark transition test. Similarly, an age-dependent decrease in locomotor activity was observed in the open field test and the elevated plus maze test, while there was an age-dependent increase in the time spent in the center area in the open field test and there were no significant differences among age groups in behavioral measures of anxiety in the elevated plus maze test. Decreases in motor performance and the auditory startle response were found in middle-aged mice compared to those in young mice. Similar behavioral changes and increased pain sensitivity, decreased social novelty preference, reduced working and spatial memory, and impaired cued fear memory were observed in old-aged mice compared to those in young mice. Prepulse inhibition was higher in middle-aged mice than in young and old-aged mice. Age-related changes in depression-related behavior were dependent on the type of test and the test time period.Conclusions: This study generally confirmed our previous report regarding age-related behavioral changes from young to middle age and expanded the previous observations by examining the behaviors of old-aged mice. Our results show age-related changes in a wide range of behaviors in mice from young to old age. Most behaviors showed gradual changes with advancing age, but some types of behaviors, such as vertical activity, prepulse inhibition, and depression-related behavior, did not show unidirectional changes with age. These findings provide basic information about the behavioral characteristics of young, middle-aged, and aged male C57BL/6J mice.