Microglia activation is essential for BMP7-mediated retinal reactive gliosis

• Main Authors: Subramanian Dharmarajan, Debra L. Fisk, Christine M. Sorenson, Nader Sheibani, Teri L. Belecky-Adams
• Format: Article
• Language: English
• Published: BMC 2017-04-01
• Series: Journal of Neuroinflammation
• Subjects: Microglia; Reactive gliosis; BMP7; Retina; Müller glia; Retinal astrocytes
• Online Access: http://link.springer.com/article/10.1186/s12974-017-0855-0

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.