Stratification of the Extent of Visual Impairment Identifies Sex-Specific Degenerative Changes in Retinal Structure and Function during Aging.

Abstract

Background: Initial manifestations of neurodegenerative ocular conditions, including age-related macular degeneration (AMD) and glaucoma, often remain undetected in the early stages and can begin after the age of 50 years with the likelihood gradually increasing each year thereafter. This study aimed to explore variances in visual and retinal function and anatomy among C57BL/6J mice, aiming to pinpoint differences between biological age and sex factors that potentially lead to the onset of vision impairment.

Methods: A longitudinal study evaluated visual acuity (VA) and contrast sensitivity (CS) using optomotor reflex (OMR), and retinal function, encompassing scotopic and photopic measurements, was recorded by electroretinogram (ERG) at 12 months of age. Tissue was subsequently harvested for histological analysis, complementing the in vivo findings. Disparities in visual function were observed between individual male and female mice, necessitating categorization of visual impairment levels to investigate further sex-specific differences in the study's aging population. Comparisons between sex and the degree of visual impairment were conducted using ANOVA followed by Tukey's or Bonferroni's post-hoc corrections and unpaired t-tests. Pearson correlation analysis determined the association between biological factors.

Results: Sex-related disparities were found in the visual function of male (n = 13) and female (n = 18) mice aged 5-12 months. Eyes were categorized by vision impairment: normal vision, or low, moderate, or severe vision loss at the end of the study. Male and female mice differed in mean contrast sensitivity, indicating less sensitivity to fine detail and moving stimuli in female mice (11-12 months old, p < 0.001). Spectral-domain optical coherence tomography (SD-OCT) revealed a thinner retinal outer nuclear layer in male mice (p < 0.0001), although this did not vary across different levels of vision impairment. ERG indicated slower retinal responses in male mice (p < 0.05), while histology showed a significant reduction in the inner plexiform layer thickness in male mice with severe vision loss (p < 0.0001). Conversely, female mice exhibited greater thinning in the photoreceptor layer when vision was unimpaired (p < 0.01).

Conclusions: The study shows that sex and extent of vision impairment influence visual and retinal health, with individual retinal layers differentially changing in thickness over time.