Browsing by Subject "BMP7"

Now showing 1 - 3 of 3
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    Microglia activation is essential for BMP7-mediated retinal reactive gliosis
    (BioMed Central, 2017) Dharmarajan, Subramanian; Fisk, Debra L.; Sorenson, Christine M.; Sheibani, Nader; Belecky-Adams, Teri L.; Department of Biology, School of Science
    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.
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    Regulation of gliosis in the mouse retina
    (2017-07-21) Dharmarajan, Subramanian; Belecky-Adams, Teri
    The glial cells of the retina aid in function and maintenance of the retina. The macroglia, Muller cells and the retinal astrocytes, become reactive following injury or disease in the retina, a response that is characterized by hypertrophy, dedifferentiation, loss of functionality, proliferation, and remodeling of tissue and extracellular matrix (ECM). The microglia which are the resident macrophages, also respond to injury/disease becoming activated, undergoing characteristic molecular and morphological changes, which include regulation of secreted factors, changes in inflammatory response and increased phagocytosis. Reactivity in Muller glia is thought to be the result of secreted signals, such as epidermal growth factor, ciliary neurotrophic factor, and broblast growth factor, which are released at the injury site to interact with quiescent glial cells. Furthermore, microglia and macroglia have been shown by some studies to interact following activation. While BMPs are known to be upregulated following injury in the CNS, little information is available concerning their role in reactive gliosis in the retina. We hypothesize that BMP7 indirectly triggers Muller gliosis by activating microglia. Using RT-qPCR, immunofluorescence and western blot, we assessed changes in gliosis markers in the mouse retinal glia following treatment with BMP. Our results showed that BMP7 was able to trigger Muller cell gliosis in the retina in vitro and in vivo. Furthermore, ablation of microglia lead to a subdued gliosis response in the mouse retina following BMP7 exposure. Thus, BMP7 triggers activation of retinal microglia in addition to the Muller glia. IFN-gamma and IL6 could play a role in microglia mediated activation of Muller glia, following exposure to BMP7. We also assessed the role of the Hippo/YAP pathway in the regulation of gliosis in the retina. We demonstrated that YAP was localized to the nucleus of the Muller cells of the retina and was upregulated in IFN-gamma induced gliosis in the mouse retina.
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    ROLE OF BMP7 IN ACTIVATION OF RETINAL MICROGLIA
    (Office of the Vice Chancellor for Research, 2016-04-08) Davis, Garrett L.
    Introduction: The retina, structure inside the eye that converts light to electrical signals, is a multilayered neural tissue, made of neurons and glial cells. The glial cells include Müller glia, astrocytes and microglia; which provide support and maintenance to the retina and act as a surveillance system that become activated during injury and disease. We have previously shown that BMP7 is able to trigger activation of the Müller glia and astrocytes. Here we aim to determine if BMP7 is able to trigger activation of retinal microglial. Methods: Mouse retinal microglia in vitro were treated with vehicle controls or BMP7 and known microglia activators interferon gamma (INF-γ) and lipopolysaccharide (LPS). Cells were labeled with DiI following treatments. Images of cells were analyzed using ImageJ/Fiji software for morphological changes in area and number of branches. Results: Cells treated with the positive controls, INF-γ and LPS, both showed an increase in cell area in comparison to vehicle-treated microglia. However, cells treated for 3 or 24 hours with LPS showed an increase in the number of branches in addition to the increase in cell area, whereas cells treated with INF-γ for 24 hours showed fewer branch numbers in addition to an increase in cell area in comparison to control cells. Microglia treated with BMP7 for 24 hours had a larger cell area and less number of branches compared to the vehicle control. Conclusion: Morphological analysis of microglia, in vitro, indicates that BMP7 triggers their activation in a manner similar to that of INF-γ. Future studies will compare in vitro results to retinas treated with BMP7.