Title

HDAC3 controls homeostasis of retina-resident microglia derived from embryonic precursors

Document Type

Conference Proceeding

Publication Date

2017

Publication Title

Journal of Immunology

Abstract

Microglia are tissue resident macrophages of the central nervous system (CNS) that function in CNS maintenance and innate immune defense. Macrophages are mediators of immune threshold and thus implicated in disease pathogenesis. Compared to research efforts on CNS microglia, relatively little is known about microglial development or homeostasis in the retina. Histone deacetylases (HDACs) are enzymes known to regulate gene expression by modifying chromatin structure. Here, we use a murine model with conditional deletion of HDAC3 induced by Colony Stimulating Factor 1 Receptor (Csf1r) Cre to determine the consequence of HDAC3 depletion on microglial development and homeostasis in the retina. Macrophages were identified using CD11b+ and F4/80bright markers. Retinal microglial populations were assessed in mice at embryonic day 14.5 (E14.5) as well as at birth and 4-weeks old. A population of CD11b+ F4/80bright retinal microglia were identified as early as E14.5, indicating that retinal microglia are derived from seeding of embryonic progenitors from the yolk sac or fetal liver. Although the frequency of retinal microglia was comparable at embryonic stage and at birth, it was significantly reduced (P = 0.008) in HDAC3 KO mice at 4 weeks old. Moreover, retinal microglia were partially radio-resistant, and could be repopulated by fetal liver cells transferred from WT but not HDAC3 KO embryos. This is the first report to show that retina-resident microglia are derived from embryonic precursors and that HDAC3 controls microglial homeostasis in adult retina. HDAC3 may serve as a promising therapeutic target for microglial immune-reactive pathologies such as age-related macular degeneration.

Volume

198

Issue

1 Supplement 1

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