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In Vivo Dynamics of Retinal Microglial Activation During Neurodegeneration: Confocal Ophthalmoscopic Imaging and Cell Morphometry in Mouse Glaucoma
Published on: May 11, 2015
Imaging microglial activation during neuroinflammation and Alzheimer's disease
Sriram Venneti1, Clayton A Wiley, Julia Kofler
1Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA. Sriram.Venneti@uphs.upenn.edu
Abstract:
Microglial activation is an important pathogenic component of neurodegenerative disease processes. This state of increased inflammation is associated not only with neurotoxic consequences but also neuroprotective effects, e.g., phagocytosis and clearance of amyloid in Alzheimer's disease. In addition, activation of microglia appears to be one of the major mechanisms of amyloid clearance following active or passive immunotherapy. Imaging techniques may provide a minimally invasive tool to elucidate the complexities and dynamics of microglial function and dysfunction in aging and neurodegenerative diseases. Imaging microglia in vivo in live subjects by confocal or two/multiphoton microscopy offers the advantage of studying these cells over time in their native environment. Imaging microglia in human subjects by positron emission tomography scanning with translocator protein-18 kDa ligands can offer a measure of the inflammatory process and a means of detecting progression of disease and efficacy of therapeutics over time.
Insights
Microglial activation plays a dual role in neurodegeneration, causing both harm and beneficial amyloid clearance. Advanced imaging techniques, like positron emission tomography, can track these inflammatory processes in vivo.
Area of Science:
- Neuroscience
- Immunology
- Medical Imaging
Background:
- Microglial activation is a key factor in neurodegenerative diseases, exhibiting both detrimental and beneficial effects.
- These inflammatory processes are implicated in conditions like Alzheimer's disease, influencing amyloid plaque dynamics.
- Microglial activity is crucial for amyloid clearance, particularly following immunotherapy.
Purpose of the Study:
- To explore the complex role of microglial activation in neurodegenerative diseases.
- To highlight the potential of in vivo imaging techniques for studying microglial function.
- To assess the utility of imaging for monitoring disease progression and therapeutic efficacy.
Main Methods:
- In vivo imaging of microglia using confocal or two/multiphoton microscopy in live subjects.
- Positron emission tomography (PET) scanning in human subjects utilizing translocator protein-18 kDa (TSPO) ligands.
- Longitudinal studies to observe microglial dynamics over time in their native environment.
Main Results:
- In vivo microscopy allows for real-time observation of microglial behavior in their natural setting.
- TSPO-targeted PET imaging provides a measure of neuroinflammation in human subjects.
- Imaging can potentially track disease progression and evaluate the effectiveness of treatments targeting microglial activation.
Conclusions:
- Microglial activation is a significant component of neurodegenerative pathogenesis with complex consequences.
- In vivo imaging offers powerful tools to investigate microglial dynamics in aging and disease.
- PET imaging of TSPO ligands can serve as a biomarker for disease monitoring and therapeutic response.
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