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Multiplexed Analysis of Retinal Gene Expression and Chromatin Accessibility Using scRNA-Seq and scATAC-Seq
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Aging reprograms the rhythmic transcriptome in the retina.

Zhijie Wang1, Lifeng Chen2, Lin Li2

  • 1Department of Retina Center, Eye Hospital and School of Ophthalmology and Optometry, Wenzhou Medical University, Hangzhou, China; National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, China; Eye Research Center, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Eye Hospital, Wenzhou Medical University, Hangzhou, China.

Experimental Eye Research
|July 1, 2025
PubMed
Summary
This summary is machine-generated.

Aging significantly alters the retina's daily gene expression patterns, impacting immune responses and pathways linked to age-related vision loss. This research reveals how aging disrupts the eye's natural rhythms.

Keywords:
Aging retinaCircadian rhythmDiurnal transcriptomeGene expression

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Area of Science:

  • Ophthalmology
  • Genomics
  • Chronobiology

Background:

  • Aging is a major risk factor for retinal degenerative diseases.
  • The impact of aging on the retina's diurnal transcriptional profile is not well understood.
  • Understanding these changes is critical due to the increasing prevalence of age-related retinal diseases.

Purpose of the Study:

  • To investigate the effects of aging on the diurnal gene expression patterns in the mouse retina.
  • To identify age-related changes in rhythmic and differentially expressed genes and pathways.

Main Methods:

  • High-throughput RNA sequencing of retinal samples from young and aged mice under a 12h:12h light-dark cycle.
  • Differential expression analysis using edgeR.
  • Rhythmicity and differential rhythmicity analysis using MetaCycle and CircaCompare packages.

Main Results:

  • 361 differentially expressed genes (DEGs) were identified, enriched in immune-related pathways.
  • Aging reduced the proportion of rhythmic genes by 28%, with notable pathway shifts.
  • Genes in RNA degradation and proteasome pathways lost rhythmicity, while immune and AMD-associated pathways gained rhythmicity in aged retinas.

Conclusions:

  • Aging profoundly alters the retina's rhythmic transcriptome, affecting gene expression timing and composition.
  • This study provides insights into the molecular mechanisms underlying age-related retinal diseases by highlighting the interplay of aging, diurnal rhythms, and gene expression.