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Subramanian Dharmarajan, Nader Sheibani, Teri Belecky-Adams; BMP7 CAN ACT AS A TRIGGER OF REACTIVE GLIOSIS IN MULLER GLIA. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5592.
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The two major glial cell types of the retina, Müller glia and retinal astrocytes, aid in function and maintenance of the retina. The glial cells become reactive following injury or disease in the retina, a response that is characterized by hypertrophy, de-differentiation, loss of functionality, proliferation, and remodeling of tissue and extracellular matrix (ECM). Reactivity in Müller glia is thought to be the result of secreted signals, such as epidermal growth factor, ciliary neurotrophic factor, and fibroblast growth factor, which are released at the injury site to interact with quiescent glial cells. 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. Our purpose in performing these studies was to clarify the role of BMP7 in reactive gliosis of the retinal glial cells.
Tissue sections and RNA from retina of the diabetic Ins2Akita mice were analyzed via real time quantitative PCR (RT-qPCR) and immunohistochemistry (IHC) for glial reactivity markers as well as BMP7 and the SMAD signaling components. Mouse retinal astrocytes and spontaneously immortalized human Müller glial MIO-M1 cells were incubated with 0.15 mM sodium peroxynitrite (a strong oxidizing agent typically released by injured neurons) for 32 h or 100 ng/ml of BMP7 for either 24 h or 36 h. Cells were lysed and total protein and RNA were prepared for Western blot and RT-qPCR analysis, respectively. Furthermore, BMP7 was administered intravitreally into normal mouse eyes and eyes were analyzed for glial reactivity by IHC and RT-qPCR.
IHC and RT-qPCR analysis showed there was reactive gliosis in the 6-week-old Ins2Akita mice retina. IHC and RT-qPCR also showed an increase in BMP7 level in the diseased eyes at this stage. A comparison between the profiles of peroxynitrite and BMP7-treated cells showed largely (but not completely) overlapping profiles of expression. Treatment with BMP7 induced a larger increase in levels of markers associated with ECM remodeling, particularly seen at the 36 h time point. A similar effect was observed in retinas of mice received BMP7 after 3 and 7 days post injection.
BMP7 plays a significant role in triggering reactive gliosis in the retina, primarily in ECM remodeling.
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