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Updated: May 2, 2026
Characterization and Isolation of Mouse Primary Microglia by Density Gradient Centrifugation
Published on: February 16, 2018
Macroglia-microglia interactions via TSPO signaling regulates microglial activation in the mouse retina
Minhua Wang1, Xu Wang, Lian Zhao
1Unit on Neuron-Glia Interactions in Retinal Disease, Mechanism of Retinal Diseases Section, Laboratory of Retinal Cell and Molecular Biology, and Biological Imaging Core, National Eye institute, National Institutes of Health, Bethesda, Maryland 20892.
Abstract:
Chronic retinal inflammation in the form of activated microglia and macrophages are implicated in the etiology of neurodegenerative diseases of the retina, including age-related macular degeneration, diabetic retinopathy, and glaucoma. However, molecular biomarkers and targeted therapies for immune cell activation in these disorders are currently lacking. To address this, we investigated the involvement and role of translocator protein (TSPO), a biomarker of microglial and astrocyte gliosis in brain degeneration, in the context of retinal inflammation. Here, we find that TSPO is acutely and specifically upregulated in retinal microglia in separate mouse models of retinal inflammation and injury. Concomitantly, its endogenous ligand, diazepam-binding inhibitor (DBI), is upregulated in the macroglia of the mouse retina such as astrocytes and Müller cells. In addition, we discover that TSPO-mediated signaling in microglia via DBI-derived ligands negatively regulates features of microglial activation, including reactive oxygen species production, TNF-α expression and secretion, and microglial proliferation. The inducibility and effects of DBI-TSPO signaling in the retina reveal a mechanism of coordinated macroglia-microglia interactions, the function of which is to limit the magnitude of inflammatory responses after their initiation, facilitating a return to baseline quiescence. Our results indicate that TSPO is a promising molecular marker for imaging inflammatory cell activation in the retina and highlight DBI-TSPO signaling as a potential target for immodulatory therapies.
Insights
Translocator protein (TSPO) and its ligand DBI are upregulated in retinal inflammation. This DBI-TSPO signaling pathway in microglia helps limit inflammatory responses, offering potential therapeutic targets for retinal diseases.
Area of Science:
- Neuroscience
- Immunology
- Ophthalmology
Background:
- Chronic retinal inflammation involving microglia and macrophages contributes to retinal neurodegenerative diseases like AMD, diabetic retinopathy, and glaucoma.
- Current limitations include the lack of specific molecular biomarkers and targeted therapies for immune cell activation in these conditions.
Purpose of the Study:
- To investigate the role of translocator protein (TSPO), a known biomarker of glial activation in the brain, within the context of retinal inflammation.
- To explore TSPO's potential as a molecular marker and therapeutic target for retinal inflammatory disorders.
Main Methods:
- Utilized mouse models of retinal inflammation and injury to examine TSPO expression in retinal microglia.
- Investigated the expression of TSPO's endogenous ligand, diazepam-binding inhibitor (DBI), in retinal macroglia (astrocytes and Müller cells).
- Assessed the functional impact of DBI-TSPO signaling on microglial activation markers (ROS production, TNF-α, proliferation).
Main Results:
- TSPO was found to be acutely and specifically upregulated in retinal microglia during inflammation and injury.
- DBI was concurrently upregulated in retinal astrocytes and Müller cells.
- DBI-TSPO signaling was shown to negatively regulate microglial activation, reducing ROS production, TNF-α secretion, and proliferation.
Conclusions:
- TSPO serves as a promising molecular marker for imaging inflammatory cell activation in the retina.
- DBI-TSPO signaling represents a potential therapeutic target for modulating immune responses and treating retinal inflammatory diseases.
