Activation of glucocorticoid receptors in Müller glia is protective to retinal neurons and suppresses microglial reactivity

Autor: Andy J. Fischer, Donika Gallina, Christopher Zelinka, Colleen M. Cebulla
Rok vydání: 2015
Předmět:
N-Methylaspartate
genetic structures
Ependymoglial Cells
Excitotoxicity
Cell Count
Nerve Tissue Proteins
Inflammation
Biology
medicine.disease_cause
Article
Retina
chemistry.chemical_compound
Receptors
Glucocorticoid
Glucocorticoid receptor
Developmental Neuroscience
Excitatory Amino Acid Agonists
medicine
Animals
Visual Pathways
Homeodomain Proteins
Neurons
Microglia
SOXB1 Transcription Factors
Retinal Detachment
Retinal
Zebrafish Proteins
Tubulin Modulators
eye diseases
Cell biology
Homeobox Protein Nkx-2.2
medicine.anatomical_structure
Animals
Newborn
Gene Expression Regulation
Neurology
chemistry
Cytokines
Fibroblast Growth Factor 2
sense organs
Injections
Intraocular
medicine.symptom
Colchicine
Chickens
Muller glia
Neuroscience
Glucocorticoid
Signal Transduction
Transcription Factors
medicine.drug
Zdroj: Experimental Neurology. 273:114-125
ISSN: 0014-4886
DOI: 10.1016/j.expneurol.2015.08.007
Popis: Reactive microglia and macrophages are prevalent in damaged retinas. Glucocorticoid signaling is known to suppress inflammation and the reactivity of microglia and macrophages. In the vertebrate retina, the glucocorticoid receptor (GCR) is known to be activated and localized to the nuclei of Müller glia (Gallina et al., 2014). Accordingly, we investigated how signaling through GCR influences the survival of neurons using the chick retina in vivo as a model system. We applied intraocular injections of GCR agonist or antagonist, assessed microglial reactivity, and the survival of retinal neurons following different damage paradigms. Microglial reactivity was increased in retinas from eyes that were injected with vehicle, and this reactivity was decreased by GCR-agonist dexamethasone (Dex) and increased by GCR-antagonist RU486. We found that activation of GCR suppresses the reactivity of microglia and inhibited the loss of retinal neurons resulting from excitotoxicity. We provide evidence that the protection-promoting effects of Dex were maintained when the microglia were selectively ablated. Similarly, intraocular injections of Dex protected ganglion cells from colchicine-treatment and protected photoreceptors from damage caused by retinal detachment. We conclude that activation of GCR promotes the survival of ganglion cells in colchicine-damaged retinas, promotes the survival of amacrine and bipolar cells in excitotoxin-damaged retinas, and promotes the survival of photoreceptors in detached retinas. We propose that suppression of microglial reactivity is secondary to activation of GCR in Müller glia, and this mode of signaling is an effective means to lessen the damage and vision loss resulting from different types of retinal damage.
Databáze: OpenAIRE
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