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Published on: November 11, 2017
Interferon γ-dependent migration of microglial cells in the retina after systemic cytomegalovirus infection
Martin S Zinkernagel1, Holly R Chinnery, Monique L Ong
1Ocular Immunology Program, Centre for Ophthalmology and Visual Science, The University of Western Australia, Perth, Australia.
Abstract:
Microglial cells are the resident macrophages of the central nervous system and participate in both innate and adaptive immune responses but can also lead to exacerbation of neurodegenerative pathologies after viral infections. Microglia in the outer layers of the retina and the subretinal space are thought to be involved in retinal diseases where low-grade chronic inflammation and oxidative stress play a role. This study investigated the effect of systemic infection with murine cytomegalovirus on the distribution and dynamics of retinal microglia cells. Systemic infection with murine cytomegalovirus elicited a significant increase in the number of microglia in the subretinal space and an accumulation of iris macrophages, along with morphological signs of activation. Interferon γ (IFN-γ)-deficient mice failed to induce changes in microglia distribution. Bone marrow chimera experiments confirmed that microglial cells in the subretinal space were not recruited from the circulating monocyte pool, but rather represented an accumulation of resident microglial cells from within the retina. Our results demonstrate that a systemic viral infection can lead to IFN-γ-mediated accumulation of microglia into the outer retinal layers and offer proof of concept that systemic viral infections alter the ocular microenvironment and therefore, may influence the course of diseases such as macular degeneration, diabetic retinopathy, or autoimmune uveitis, where low-grade inflammation is implicated.
Insights
Systemic viral infections cause retinal microglia to accumulate in outer eye layers, driven by interferon gamma (IFN-γ). This accumulation of resident microglia, not from blood monocytes, impacts eye diseases involving inflammation.
Area of Science:
- Neuroscience
- Immunology
- Ophthalmology
Background:
- Microglial cells are key immune cells in the central nervous system, including the retina.
- These cells can contribute to neurodegeneration after viral infections.
- Retinal microglia are implicated in inflammatory eye diseases.
Purpose of the Study:
- To investigate how systemic murine cytomegalovirus infection affects retinal microglia distribution and dynamics.
- To understand the role of interferon gamma (IFN-γ) in these changes.
- To determine the origin of accumulating microglia in the subretinal space.
Main Methods:
- Systemic infection of mice with murine cytomegalovirus.
- Analysis of microglia distribution and morphology in retinal and iris tissues.
- Use of interferon gamma (IFN-γ)-deficient mice.
- Bone marrow chimera experiments to trace cell origins.
Main Results:
- Murine cytomegalovirus infection significantly increased subretinal space microglia and iris macrophage accumulation.
- Activated microglia showed morphological changes.
- IFN-γ-deficient mice did not exhibit altered microglia distribution.
- Bone marrow chimeras showed subretinal microglia originated from resident retinal cells, not circulating monocytes.
Conclusions:
- Systemic viral infection triggers IFN-γ-mediated accumulation of resident microglia in the outer retina.
- This demonstrates that systemic viral infections alter the ocular microenvironment.
- These findings suggest a mechanism influencing inflammatory eye conditions like macular degeneration and diabetic retinopathy.
