Cited by 131Retinal Diseases and TreatmentsRetinal Development and DisordersOcular Diseases and Behçet’s Syndrome

Immune Activation in Retinal Aging: A Gene Expression Study

Chen, Mei, Muckersie, Elizabeth, Forrester, John V., Xu, Heping·2010·Investigative Opthalmology & Visual Science

Abstract

PURPOSE: To investigate changes in gene expression during aging of the retina in the mouse. METHODS: Total RNA was extracted from the neuroretina of young (3-month-old) and old (20-month-old) mice and processed for microarray analysis. Age-related, differentially expressed genes were assessed by the empiric Bayes shrinkage-moderated t-statistics METHOD: Statistical significance was based on dual criteria of a ratio of change in gene expression >2 and a P < 0.01. Differential expression in 11 selected genes was further verified by real-time PCR. Functional pathways involved in retinal aging were analyzed by an online software package (DAVID-2008) in differentially expressed gene lists. Age-related changes in differential expression in the identified retinal molecular pathways were further confirmed by immunohistochemical staining of retinal flat mounts and retinal cryosections. RESULTS: With aging of the retina, 298 genes were upregulated and 137 genes were downregulated. Functional annotation showed that genes linked to immune responses (Ir genes) and to tissue stress/injury responses (TS/I genes) were most likely to be modified by aging. The Ir genes affected included those regulating leukocyte activation, chemotaxis, endocytosis, complement activation, phagocytosis, and myeloid cell differentiation, most of which were upregulated, with only a few downregulated. Increased microglial and complement activation in the aging retina was further confirmed by confocal microscopy of retinal tissues. The most strongly upregulated gene was the calcitonin receptor (Calcr; >40-fold in old versus young mice). CONCLUSIONS: The results suggest that retinal aging is accompanied by activation of gene sets, which are involved in local inflammatory responses. A modified form of low-grade chronic inflammation (para-inflammation) characterizes these aging changes and involves mainly the innate immune system. The marked upregulation of Calcr in aging mice most likely reflects this chronic inflammatory/stress response, since calcitonin is a known systemic biomarker of inflammation/sepsis.

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Crossref · 10.1167/iovs.09-5103

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Authors
Chen, M., Muckersie, E., Forrester, J. V., & Xu, H.
Affiliations
  • Queen's University Belfast (GB)
  • University of Aberdeen (GB)
Venue
Investigative Opthalmology & Visual Science
Published
2010-11-01
Volume
51
Issue
11
Pages
5888
ISSN
  • 0146-0404 (ISSN-L)
  • 1552-5783
OpenAlex
W2096107242
Cited by
130
References
41
Citations by year
2026: 3 · 2025: 7 · 2024: 13 · 2023: 7 · 2022: 15 · 2021: 22 · 2020: 3 · 2019: 2 · 2018: 7 · 2017: 8 · 2016: 4 · 2015: 9 · 2014: 5 · 2013: 9 · 2012: 10
FWCI
8.81
Type
journal article
Language
en
Open access
closed
Locations
  • Investigative Ophthalmology & Visual Science (publishedVersion, public-domain)
  • PubMed (publishedVersion)
  • Research Portal (Queen's University Belfast) (submittedVersion)
Topics
  • Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinal Development and Disorders
  • Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
Keywords
retinal aging, neuroretina, gene expression, immune activation, chronic inflammation, innate immunity, microglia, complement activation, calcitonin receptor, calcitonin, leukocyte activation
MeSH terms
Aging, Animals, Eye Proteins, Genes, MHC Class II, Male, Mice, Inbred C57BL, Retina, RNA, Gene Expression, Microscopy, Confocal, Fluorescent Antibody Technique, Indirect, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, Mice

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