Purpose The focus of this study was to determine whether bone morphogenetic proteins (BMPs) trigger reactive gliosis in retinal astrocytes and/or Mller glial cells. a reactive gliosis response 7 days after injection. Findings BMP7 induced changes in levels of mRNA and protein markers typically associated with reactive gliosis in retinal astrocytes and Mller glial cells, including glial fibrillary acidic protein (GFAP), glutamine synthetase (GS), a subset of chondroitin sulfate proteoglycans (CSPGs), matrix metalloproteinases (MMPs), and other molecules. Introduction The mature mammalian retina contains several types of macroglial cells, including Mller glia, retinal astrocytes, and in some cases oligodendrocytes and nonastrocytic retinal glial cells (NIRG) [1-4]. The Mller glia arise from neural retinal progenitor cells late in retinal development. The Mller cells span nearly the entire width of the retina from the outer limiting membrane, where Mller processes form connections with photoreceptors, to the inner limiting membrane, where Mller and retinal astrocyte processes form the boundary between the retina and the vitreous [5]. The retinal astrocytes migrate into the retina from the developing optic nerve; their cell body populate the nerve fiber layer (NFL) and send processes into the ganglion cell layer (GCL) [6]. While the origins of NIRG cells are unknown, they have been hypothesized to migrate from the developing optic nerve [2]. Both the Mller glia and retinal astrocytes have been shown to play very important functions in supporting and protecting 867160-71-2 manufacture the retinal neurons. For instance, both are crucial to the formation of the 867160-71-2 manufacture blood-retinal hurdle, neurotransmitter recycling, removal of toxins, and growth factor supplementation of ganglion cells [7-10]. An important house of glial cells is usually their response to any damage/injury to nearby neurons; this response is usually known as reactive gliosis. The Mller glia and retinal and optic nerve astrocytes become reactive in numerous disease says such as glaucoma, retinal ischemia, and diabetes [11,12]. One particularly interesting aspect of gliosis is usually the molecular diversity in the reaction of the astrocytes to numerous disease says and injuries [13-15]. For instance, insult-dependent increases or decreases in the manifestation of glial fibrillary acidic protein (GFAP), vimentin, glutamine synthetase (GS), and extracellular matrix (ECM) molecules have been noted in Mller glial cells and astrocytes [11,16-18]. This variance has been hypothesized to be the result of the release of numerous factors that drive different aspects of reactive gliosis [14,19,20]. Further diversity in the response is usually launched by virtue of the fact that reactive astrocytes fall on a continuum from moderate to severe, in which cells display one or more of the following: hypertrophy, dedifferentiation, loss of function, proliferation, inflammation, Rabbit Polyclonal to TNFRSF10D and remodeling of the tissue and vasculature [21,22]. Furthermore, some of the cellular responses are dual in nature. An example of this is usually the hypertrophy of Mller glia and astrocytes that results from an increase in the intermediate filaments GFAP and vimentin. On one hand, the hypertrophied cellular processes may form a hurdle around the hurt region, inhibiting the spread of inflammatory molecules into healthy tissue; on the other, these processes can also block the regeneration of axons and synapses [22]. Severe reactive gliosis is usually also accompanied by tissue remodeling that includes excessive hypertrophy of the glial cell body and processes, as well as the turnover of the ECM to a regeneration-inhibitory matrix, together referred to as a glial scar. One of the major components of the ECM is usually chondroitin sulfate proteoglycans (CSPGs), a family of molecules that includes neurocan (Ncan), phosphacan (Pcan), versican, aggrecan, brevican, nerve/glial antigen 2 (NG2), and CD44 [23]. Although 867160-71-2 manufacture the mechanisms and causes have not been completely characterized, a variety of growth factor signaling mechanisms have been found to be important in reactive gliosis, such as those of epidermal growth factor (EGF), fibroblast growth factor (FGF), tumor necrosis factor- (TNF-), ciliary neurotrophic factor (CNTF), insulin, and WNTs [20,22,24]. Data from several laboratories have indicated that each pathway may regulate specific characteristics associated with reactive gliosis. For instance, CNTF appears to be associated with the upregulation of GFAP, while EGF and FGF are associated with proliferation [17,25]. Studies using different central nervous system (CNS) injury models have shown that the bone morphogenetic protein (BMP) pathway is usually upregulated at the site of injury in the CNS and can trigger reactive gliosis [26-28]. Furthermore, BMP receptor 1A (BMPR1A) has.