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Published in: Journal of Neuroinflammation 1/2017

Open Access 01-12-2017 | Research

Microglia activation is essential for BMP7-mediated retinal reactive gliosis

Authors: Subramanian Dharmarajan, Debra L. Fisk, Christine M. Sorenson, Nader Sheibani, Teri L. Belecky-Adams

Published in: Journal of Neuroinflammation | Issue 1/2017

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Abstract

Background

Our previous studies have shown that BMP7 is able to trigger activation of retinal macroglia. However, these studies showed the responsiveness of Müller glial cells and retinal astrocytes in vitro was attenuated in comparison to those in vivo, indicating other retinal cell types may be mediating the response of the macroglial cells to BMP7. In this study, we test the hypothesis that BMP7-mediated gliosis is the result of inflammatory signaling from retinal microglia.

Methods

Adult mice were injected intravitreally with BMP7 and eyes harvested 1, 3, or 7 days postinjection. Some mice were treated with PLX5622 (PLX) to ablate microglia and were subsequently injected with control or BMP7. Processed tissue was analyzed via immunofluorescence, RT-qPCR, or ELISA. In addition, cultures of retinal microglia were treated with vehicle, lipopolysaccharide, or BMP7 to determine the effects of BMP7-isolated cells.

Results

Mice injected with BMP7 showed regulation of various inflammatory markers at the RNA level, as well as changes in microglial morphology. Isolated retinal microglia also showed an upregulation of BMP-signaling components following treatment. In vitro treatment of retinal astrocytes with conditioned media from activated microglia upregulated RNA levels of gliosis markers. In the absence of microglia, the mouse retina showed a subdued gliosis and inflammatory response when exposed to BMP7.

Conclusions

Gliosis resulting from BMP7 is mediated through an inflammatory response from retinal microglia.
Appendix
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Metadata
Title
Microglia activation is essential for BMP7-mediated retinal reactive gliosis
Authors
Subramanian Dharmarajan
Debra L. Fisk
Christine M. Sorenson
Nader Sheibani
Teri L. Belecky-Adams
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2017
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-017-0855-0

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