“Aging mouse: functional vision decline and related molecular changes”

Abstract

Purpose : Aging leads to visual deterioration. Little is known about the molecular changes correlated with vision decline. Heterogeneity of retinal layers creates a challenge for isolated assessment. We aimed to identify age-related functional decline in mouse vision and examine aging impact at the molecular level.

Methods : Visual function was tested in 3-month and 18-month old mice using a comprehensive approach: 1.Visual acuity was assessed with Optomotor response (OMR) assay. 2.Rod and cone photoreceptor function was measured with scotopic and photopic electroretinography (ERG). 3.Visual system physiology was tested by performing recordings of Visually Evoked Potentials (VEPs). 4.RGC activity was assessed with recording of pattern ERG (PERG).
For molecular analysis, the bulk RNAseq was performed. Gene set enrichment analysis was applied for differential expression comparisons between two groups of RNA-Seq samples.

Results : Optomotor response and ERG responses were significantly decreased in 18 month old animals in both scotopic and photopic conditions in comparison to 3-month old animals (p-value<0.0001). We observed a significant reduction of VEPs amplitudes recorded in the superior colliculus and the primary visual cortex. Interestingly pattern ERG recordings showed no statistical significance between young and old animals. Analysis of molecular changes revealed 1451 genes up-regulated (log2 fold>=1, FDR<0.05) and 2394 genes down-regulated (log2 fold<=-1, FDR<0.05) upon natural aging. Upregulated pathways in aged animals included inflammation, TNFa signaling and apoptosis. Downregulated pathways included DNA repair and fatty acid metabolism pathways.

Conclusions : Aging leads to a reduction in vision in mice. Significant decrease in photoreceptor function measured by ERG is coherent with behavioral measurements (OMR). Visual information processing is affected by aging; however, RGC function is preserved in old mice. The analysis of age-related molecular changes reveals transcriptional pathways impacted in aged retinas. Connecting functional and molecular approaches will lead to a better understanding of age-related diseases and may lead to novel therapies in the future.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.