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Bone morphogenetic protein 7 regulates reactive gliosis in retinal astrocytes and Müller glia
Subramanian Dharmarajan1, Zafer Gurel2, Shoujian Wang2
1Department of Biology, Indiana University-Purdue University Indianapolis,, Indianapolis, IN ; Center for Regenerative Biology and Medicine, Indiana University- Purdue University Indianapolis, Indianapolis, IN.
Purpose:
The focus of this study was to determine whether bone morphogenetic proteins (BMPs) trigger reactive gliosis in retinal astrocytes and/or Müller glial cells.
Methods:
Retinal astrocytes and the Müller glial cell line MIO-M1 were treated with vehicle, BMP7, or BMP4. Samples from the treated cells were analyzed for changes in gliosis markers using reverse transcriptase - quantitative PCR (RT-qPCR) and western blotting. To determine potential similarities and differences in gliosis states, control and BMP-treated cells were compared to cells treated with sodium peroxynitrite (a strong oxidizing agent that will bring about some aspects of gliosis). Last, mature mice were microinjected intravitreally with BMP7 and analyzed for changes in gliosis markers using RT-qPCR, western blotting, and immunohistochemistry.
Results:
Treatment of retinal astrocyte cells and Müller glial cells with BMP7 regulated various reactive gliosis markers. When compared to the response of cells treated with sodium peroxynitrite, the profiles of gliosis markers regulated due to exposure to BMP7 were similar. However, as expected, the profiles including the oxidative agent and growth factor were not identical. Treatment of cells with BMP4, however, showed an attenuated response in comparison to peroxynitrite and BMP7 treatment. Injection of BMP7 into the mouse retina also triggered a reactive gliosis response 7 days after injection.
Conclusions:
BMP7 induced changes in levels of mRNA and protein markers typically associated with reactive gliosis in retinal astrocytes and Müller glial cells, including glial fibrillary acidic protein (GFAP), glutamine synthetase (GS), a subset of chondroitin sulfate proteoglycans (CSPGs), matrix metalloproteinases (MMPs), and other molecules.
Insights
Bone morphogenetic proteins (BMPs), specifically BMP7, trigger reactive gliosis in retinal astrocytes and Müller glial cells. This involves changes in key markers like GFAP and GS, indicating potential roles in retinal cell responses.
Area of Science:
- Ophthalmology
- Neuroscience
- Cell Biology
Background:
- Reactive gliosis is a complex cellular response in the retina.
- Bone morphogenetic proteins (BMPs) are implicated in various cellular processes.
- Understanding BMPs' role in glial cell activation is crucial for retinal research.
Purpose of the Study:
- To investigate if bone morphogenetic proteins (BMPs) induce reactive gliosis.
- To examine the effects of BMP7 and BMP4 on retinal astrocytes and Müller glial cells.
- To compare BMP-induced gliosis markers with those induced by oxidative stress.
Main Methods:
- Retinal astrocytes and MIO-M1 Müller glial cells were treated with BMP7, BMP4, or vehicle.
- Gene and protein expression of gliosis markers were analyzed using RT-qPCR and western blotting.
- In vivo studies involved intravitreal injection of BMP7 in mice, followed by molecular and histological analysis.
Main Results:
- BMP7 treatment upregulated several reactive gliosis markers in both cell types.
- BMP7-induced gliosis markers showed similarities but also differences compared to sodium peroxynitrite treatment.
- BMP4 exhibited a less pronounced effect than BMP7 or sodium peroxynitrite.
- Intravitreal BMP7 injection in mice induced a reactive gliosis response.
Conclusions:
- BMP7 significantly alters mRNA and protein levels of reactive gliosis markers in retinal astrocytes and Müller glial cells.
- Key markers affected include glial fibrillary acidic protein (GFAP), glutamine synthetase (GS), chondroitin sulfate proteoglycans (CSPGs), and matrix metalloproteinases (MMPs).
- These findings highlight BMP7's role in modulating glial cell states relevant to retinal physiology and pathology.
