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Updated: Jun 15, 2026
In Vivo Dynamics of Retinal Microglial Activation During Neurodegeneration: Confocal Ophthalmoscopic Imaging and Cell Morphometry in Mouse Glaucoma
Published on: May 11, 2015
Microglia in neurodegenerative disease
V Hugh Perry1, James A R Nicoll, Clive Holmes
1School of Biological Sciences, University of Southampton, Building 62, Boldrewood Campus, Southampton SO16 7PX, UK. v.h.perry@soton.ac.uk
Abstract:
Microglia, the resident macrophages of the CNS, are exquisitely sensitive to brain injury and disease, altering their morphology and phenotype to adopt a so-called activated state in response to pathophysiological brain insults. Morphologically activated microglia, like other tissue macrophages, exist as many different phenotypes, depending on the nature of the tissue injury. Microglial responsiveness to injury suggests that these cells have the potential to act as diagnostic markers of disease onset or progression, and could contribute to the outcome of neurodegenerative diseases. The persistence of activated microglia long after acute injury and in chronic disease suggests that these cells have an innate immune memory of tissue injury and degeneration. Microglial phenotype is also modified by systemic infection or inflammation. Evidence from some preclinical models shows that systemic manipulations can ameliorate disease progression, although data from other models indicates that systemic inflammation exacerbates disease progression. Systemic inflammation is associated with a decline in function in patients with chronic neurodegenerative disease, both acutely and in the long term. The fact that diseases with a chronic systemic inflammatory component are risk factors for Alzheimer disease implies that crosstalk occurs between systemic inflammation and microglia in the CNS.
Insights
Microglia, immune cells in the brain, change in response to injury and disease. Their persistent activation suggests an immune memory, impacting neurodegeneration and Alzheimer's disease risk.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Microglia are the central nervous system's (CNS) resident macrophages.
- They are highly sensitive to brain injury and disease, adopting an activated state.
- Activated microglia exhibit diverse phenotypes dependent on injury type and may serve as diagnostic markers.
Purpose of the Study:
- To explore the role of microglial activation in neurodegenerative diseases.
- To investigate the concept of innate immune memory in microglia.
- To examine the influence of systemic inflammation on microglial phenotype and neurodegenerative disease progression.
Main Methods:
- Analysis of microglial morphology and phenotype changes in response to CNS insults.
- Review of preclinical models investigating systemic manipulation effects on neurodegeneration.
- Examination of the association between systemic inflammation and cognitive decline in neurodegenerative disease patients.
Main Results:
- Microglia alter morphology and phenotype in response to brain injury, indicating diverse functional states.
- Activated microglia can persist long-term, suggesting an innate immune memory.
- Systemic inflammation impacts microglial phenotype and is linked to disease progression and Alzheimer's disease risk.
Conclusions:
- Microglia play a critical role in CNS injury and neurodegenerative diseases.
- Microglial immune memory is a significant factor in disease pathology.
- Systemic inflammation and CNS microglia crosstalk influences neurodegeneration and Alzheimer's disease.
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