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Subramanian Dharmarajan, Nader Sheibani, Teri L Belecky-Adams; BMP-7 Activation of Microglia Drives Reactive Retinal Gliosis. Invest. Ophthalmol. Vis. Sci. 2016;57(12):2223.
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© ARVO (1962-2015); The Authors (2016-present)
Retinal microglia are key innate immune cells within the central nervous system. Upon injury and damage, they become “activated”, undergoing characteristic molecular and morphological changes. The primary retinal glial cells, Müller glia, as well as the retinal astrocytes also undergo activation, a process called reactive gliosis, following retinal injury. Our lab has previously shown that BMP7 is able to trigger Müller cell gliosis; however, the mechanism is unclear. We hypothesize that BMP7 indirectly triggers Müller gliosis by activating microglia.
For ablation of microglia, mice were fed with a chow containing 1,200 ppm PLX5622 (Plexxikon Inc). BMP7 or vehicle was intravitreally injected into microglia ablated mice, and eyes were harvested 3 or 7 days post injection. Tissue was analyzed for gliosis markers via immunohistochemistry (IHC) or RT-qPCR. Mouse retinal microglial cells in vitro as well as mature mice were exposed to vehicle, INF-γ (a known activator of microglia) or BMP7 to test and compare activation. Samples were analyzed by IHC, RT-qPCR or ELISA for activation markers and morphological changes.
Microglia were ablated in the mouse retina 14 days after shifting to the PLX chow feed, without any loss of any other cell type. Intravitreal BMP7 injections in these mice showed a decreased gliosis response. BMP7 treatment of isolated retinal microglia showed an increase in mRNA levels of granulocyte macrophage colony stimulating factor, interferon gamma (INF-γ), and interleukin-6 (IL6) in comparison to vehicle-treated cells. Furthermore, an increase in the morphological characteristics found in activated microglial cells was also observed following BMP7 treatment in vitro and in vivo.
Our findings indicate that microglia are essential for Müller cell gliosis. BMP7 triggers activation of retinal microglia in addition to the Müller glia. Furthermore, INF-γ and IL6 could play a role in microglia mediated activation of Müller glia, following exposure to BMP7.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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