Gene expression changes in aging retinal microglia: relationship to microglial support functions and regulation of activation

Neurobiol Aging. 2013 Oct;34(10):2310-21. doi: 10.1016/j.neurobiolaging.2013.03.022. Epub 2013 Apr 19.


Microglia, the resident immune cells of the central nervous system (CNS), are thought to contribute to the pathogenesis of age-related neurodegenerative disorders. It has been hypothesized that microglia undergo age-related changes in gene expression patterns that give rise to pathogenic phenotypes. We compared the gene expression profiles in microglia isolated ex vivo from the retinas of mice ranging from early adulthood to late senescence. We discovered that microglial gene expression demonstrated progressive change with increasing age, and involved genes that regulate microglial supportive functions and immune activation. Molecular pathways involving immune function and regulation, angiogenesis, and neurotrophin signaling demonstrated age-related change. In particular, expression levels of complement genes, C3 and CFB, previously associated with age-related macular degeneration (AMD), increased with aging, suggesting that senescent microglia may contribute to complement dysregulation during disease pathogenesis. Taken together, senescent microglia demonstrate age-related gene expression changes capable of altering their constitutive support functions and regulation of their activation status in ways relating to neuroinflammation and neurodegeneration in the CNS.

Keywords: Activation; Aging; Angiogenesis; Complement; Gene expression; Microarray; Microglia; Neurotrophic factors; Retina; Senescence.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / genetics*
  • Aging / pathology
  • Aging / physiology
  • Animals
  • Central Nervous System Diseases / genetics
  • Complement C3c
  • Complement Factor B
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental*
  • Immunity / genetics*
  • Inflammation / genetics
  • Macular Degeneration / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microglia / pathology
  • Microglia / physiology*
  • Nerve Growth Factors / physiology
  • Neurodegenerative Diseases / genetics
  • Retina / cytology*
  • Retina / pathology*
  • Signal Transduction / genetics


  • Nerve Growth Factors
  • Complement C3c
  • Complement Factor B