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The role of Muller cell glucocorticoid signaling in diabetic retinopathy.
Graefes Arch. Clin. Exp. Ophthalmol. 258, 221–230 (2020)
Diabetic retinopathy (DR) is a sight-threatening complication associated with the highly prevalent diabetes disorder. Both the microvascular damage and neurodegeneration detected in the retina caused by chronic hyperglycemia have brought special attention to Muller cells, the major macroglia of the retina that are responsible for retinal homeostasis. Given the role of glucocorticoid signaling in anti-inflammatory responses and the almost exclusive expression of glucocorticoid receptors (GRs) in retinal Muller cells, administration of corticosteroid agonists as a potential treatment option has been widely studied. Although these approaches have been moderately efficacious in treating or de-escalating DR pathomechanisms, there are various side effects and gaps of knowledge with regard to introducing exogenous glucocorticoids to the diseased retina. In this paper, we provide a review of the literature concerning the available evidence for the role of Muller cell glucocorticoid signaling in DR and we discuss previously investigated approaches in modulating this system as possible treatment options. Furthermore, we propose a novel alternative to the available choices of treatment by using gene therapy as a tool to regulate the expression of GR in retinal Muller cells. Upregulating GR expression allows for induced glucocorticoid signaling with more enduring effects compared to injection of agonists. Hence, repetitive injections would no longer be required. Lastly, side effects of glucocorticoid therapy such as glucocorticoid resistance of GR following chronic exposure to excess ligands or agonists can be avoided.
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Publication type
Article: Journal article
Document type
Review
Keywords
Diabetic Retinopathy ; Glucocorticoid Signaling ; Muller Cells ; Gene Therapy; Endothelial Growth-factor; Oxidative Stress; Gene-transfer; Glial-cells; Molecular-mechanisms; Factor Expression; Vascular Leakage; Retinal Neurons; Animal-models; Macular Edema
ISSN (print) / ISBN
0721-832X
e-ISSN
1435-702X
Quellenangaben
Volume: 258,
Issue: 2,
Pages: 221–230
Publisher
Springer
Publishing Place
Berlin ; Heidelberg [u.a.]
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
CF Metabolomics & Proteomics (CF-MPC)