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Updated: May 12, 2026

In Vivo Dynamics of Retinal Microglial Activation During Neurodegeneration: Confocal Ophthalmoscopic Imaging and Cell Morphometry in Mouse Glaucoma
Published on: May 11, 2015
Gene expression changes in aging retinal microglia: relationship to microglial support functions and regulation of
Wenxin Ma1, Radu Cojocaru, Norimoto Gotoh
1Unit on Neuron-Glia Interactions in Retinal Disease, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Abstract:
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.
Insights
Senescent microglia exhibit age-related gene expression changes impacting CNS immune functions. These changes in microglia, the brain's immune cells, may drive neuroinflammation and neurodegeneration in aging.
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- Microglia are central nervous system (CNS) immune cells implicated in neurodegenerative diseases.
- Age-related changes in microglial gene expression are hypothesized to cause pathogenic phenotypes.
Purpose of the Study:
- To investigate age-related gene expression changes in microglia.
- To identify specific molecular pathways affected by microglial aging.
Main Methods:
- Microglia were isolated ex vivo from mouse retinas across a lifespan.
- Gene expression profiles were analyzed to identify age-dependent alterations.
Main Results:
- Microglial gene expression showed progressive changes with age, affecting immune function and supportive roles.
- Age-related changes were observed in pathways of immune regulation, angiogenesis, and neurotrophin signaling.
- Expression of complement genes C3 and CFB increased with aging, potentially linking senescent microglia to complement dysregulation in diseases like age-related macular degeneration (AMD).
Conclusions:
- Senescent microglia display age-related gene expression modifications.
- These modifications can alter microglial functions, impacting CNS neuroinflammation and neurodegeneration.
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