Pfaller, Anna M. and Kaplan, Lew and Carido, Madalena and Grassmann, Felix and Diaz-Lezama, Nundehui and Ghaseminejad, Farhad and Wunderlich, Kirsten A. and Glaenzer, Sarah and Bludau, Oliver and Pannicke, Thomas and Weber, Bernhard H. F. and Koch, Susanne F. and Bonev, Boyan and Hauck, Stefanie M. and Grosche, Antje (2024) The glucocorticoid receptor as a master regulator of the Müller cell response to diabetic conditions in mice. JOURNAL OF NEUROINFLAMMATION, 21 (1): 33. ISSN , 1742-2094
Full text not available from this repository. (Request a copy)Abstract
Diabetic retinopathy (DR) is considered a primarily microvascular complication of diabetes. Muller glia cells are at the centre of the retinal neurovascular unit and play a critical role in DR. We therefore investigated Muller cell-specific signalling pathways that are altered in DR to identify novel targets for gene therapy. Using a multi-omics approach on purified Muller cells from diabetic db/db mice, we found the mRNA and protein expression of the glucocorticoid receptor (GR) to be significantly decreased, while its target gene cluster was down-regulated. Further, oPOSSUM TF analysis and ATAC- sequencing identified the GR as a master regulator of Muller cell response to diabetic conditions. Cortisol not only increased GR phosphorylation. It also induced changes in the expression of known GR target genes in retinal explants. Finally, retinal functionality was improved by AAV-mediated overexpression of GR in Muller cells. Our study demonstrates an important role of the glial GR in DR and implies that therapeutic approaches targeting this signalling pathway should be aimed at increasing GR expression rather than the addition of more ligand.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ENDOTHELIAL GROWTH-FACTOR; MULLER GLIAL-CELLS; RETINAL BARRIER BREAKDOWN; MEMBRANE CONDUCTANCE; FACTOR EXPRESSION; OXIDATIVE STRESS; MOUSE MODELS; DB/DB MOUSE; ACTIVATION; DYSFUNCTION; Diabetic retinopathy; Muller glia; mRNA expression profiling; Glucocorticoid receptor signalling; Proteomic analysis |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Humangenetik |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 16 Jan 2026 07:57 |
| Last Modified: | 16 Jan 2026 07:57 |
| URI: | https://pred.uni-regensburg.de/id/eprint/64726 |
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