Interferon gamma-dependent migration of microglial cells in the retina after systemic cytomegalovirus infection

Martin S Zinkernagel, Holly Rose Chinnery, Monique Ong, Claire Petitjean, Valentina Voigt, Samuel McLenachan, Paul Gerard McMenamin, Geoffrey R Hill, John V Forrester, Matthew E Wikstrom, Mariapia Degli-Esposti

Research output: Contribution to journalArticleResearchpeer-review

22 Citations (Scopus)

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 gamma (IFN-gamma)-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-gamma-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.
Original languageEnglish
Pages (from-to)875 - 885
Number of pages11
JournalAmerican Journal of Pathology
Volume182
Issue number3
DOIs
Publication statusPublished - 2013

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