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Donika Gallina, Andrew Fischer; The Role of Glucocorticoid Receptor Signaling in Normal and Damaged Avian Retina. Invest. Ophthalmol. Vis. Sci. 2013;54(15):6072.
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© ARVO (1962-2015); The Authors (2016-present)
Glucocorticoids are steroid hormones that are important for maintenance of basal and stress-related tissue homeostasis. Cortisol, the endogenous ligand of glucocorticoid receptor (GCR), is known to stimulate the expression of glutamine synthetase (GS) in developing Müller glia in embryonic chick retinas. The purpose of this study was to investigate whether GCR-signaling influences the phenotype of mature retinal glia in normal retina, and whether GCR-signaling inhibits proliferation of glia-derived progenitors in damaged retina.
We used immunohistochemistry to study the expression pattern of GCR in the retinas of different vertebrates. We performed intraocular injections of the GCR agonist dexamethasone followed by assays for proliferation, neuronal survival and for glial phenotype in normal and damaged retinas. qRT-PCR was used to measure retinal levels of cytokines. Retinal damage was induced by intraocular injection of N-Methyl-D-aspartate (NMDA).
We found that the pattern of GCR expression is highly conserved among the retinas of human, mouse, dog, guinea pig and chick. GCR is consistently expressed in the Müller glia in the retina. In avian retina, GCR is also expressed in non astrocytic inner retinal glial cells (NIRG) and the retinal progenitors in the circumferential marginal zone. Activation of GCR signaling reduced retinal levels of pro-inflammatory cytokines and inhibited microglia reactivity in normal retina. Further, dexamethasone injections protected retinal neurons against NMDA-induced damage. Injections of dexamethasone after NMDA-induced retinal damage inhibited the formation of proliferating Müller glia-derived progenitors.
Since GCR is expressed by Müller glia and NIRG cells, it is possible that the effects of dexamathesone on microglia are secondary to GCR-signaling in Müller glia or NIRG cells. We propose that GCR-signaling in Müller glia may reduce retinal levels of pro-inflammatory cytokines, and this effect may diminish the damaging effects of NMDA upon retinal neurons. Our data suggests that GCR-signaling acts in opposition to signals that stimulate the de-differentiation and proliferation of Müller glia. Our discovery suggests a role of GCR-signaling in retina regeneration. This research will hopefully lead to the development of novel therapies for the treatment of hereditary and acquired retina degeneration.
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