The role of Müller cell glucocorticoid signaling in diabetic retinopathy.

Publisher: Springer-Verlag Country of Publication: Germany NLM ID: 8205248 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1435-702X (Electronic) Linking ISSN: 0721832X NLM ISO Abbreviation: Graefes Arch Clin Exp Ophthalmol Subsets: MEDLINE

Original Publication: Berlin ; New York : Springer-Verlag, c1982-

Diabetic Retinopathy/*metabolism ; Ependymoglial Cells/*metabolism ; Receptors, Glucocorticoid/*metabolism ; Retina/*metabolism; Animals ; Diabetic Retinopathy/pathology ; Humans ; Retina/pathology ; Signal Transduction

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 Müller 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 Müller 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 Müller 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 Müller 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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GR 4403/2-1 Deutsche Forschungsgemeinschaft; HA6014/5-1 Deutsche Forschungsgemeinschaft; UBC-Germany Scholarship University of British Columbia

Keywords: Diabetic retinopathy; Gene therapy; Glucocorticoid signaling; Müller cells

0 (Receptors, Glucocorticoid)

Date Created: 20191118 Date Completed: 20201201 Latest Revision: 20201201

20231215

10.1007/s00417-019-04521-w

31734719