title: Microglia activation is essential for BMP7-mediated retinal reactive gliosis.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Gliosis resulting from BMP7 is mediated through an inflammatory response from retinal microglia.
authors.affiliation: Department of Biology, Indiana University-Purdue University Indianapolis, 723 W Michigan St, SL306, Indianapolis, IN, 46202, USA.|Center for Developmental and Regenerative Biology, Indiana University-Purdue University Indianapolis, 723 W Michigan St, Indianapolis, IN, 46202, USA.
authors.forename: Subramanian
authors.initials: S
authors.lastname: Dharmarajan
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, 1111 Highland Avenue, 9453 WIMR, Madison, WI, 53705, USA.
authors.forename: Debra L
authors.initials: DL
authors.lastname: Fisk
authors.affiliation: Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, 1111 Highland Avenue, 9453 WIMR, Madison, WI, 53705, USA.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Sorenson
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, 1111 Highland Avenue, 9453 WIMR, Madison, WI, 53705, USA.
authors.forename: Nader
authors.initials: N
authors.lastname: Sheibani
authors.affiliation: Department of Biology, Indiana University-Purdue University Indianapolis, 723 W Michigan St, SL306, Indianapolis, IN, 46202, USA. tbadams@iupui.edu.|Center for Developmental and Regenerative Biology, Indiana University-Purdue University Indianapolis, 723 W Michigan St, Indianapolis, IN, 46202, USA. tbadams@iupui.edu.
authors.forename: Teri L
authors.initials: TL
authors.lastname: Belecky-Adams
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D055419:Bone Morphogenetic Protein 7 / Q000633:toxicity*; D002478:Cells, Cultured; D005911:Gliosis / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D012160:Retina / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology
chemical_list: D055419:Bone Morphogenetic Protein 7; C525820:bmp7 protein, mouse
keywords: BMP7; Microglia; Müller glia; Reactive gliosis; Retina; Retinal astrocytes