The role of Müller cell glucocorticoid signaling in diabetic retinopathy

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...

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Bibliographic Details
Published in:Graefe's archive for clinical and experimental ophthalmology 2020-02, Vol.258 (2), p.221-230
Main Authors: Ghaseminejad, Farhad, Kaplan, Lew, Pfaller, Anna M., Hauck, Stefanie M., Grosche, Antje
Format: Article
Language:English
Subjects:
Agonists
Chronic exposure
Corticosteroids
Diabetes
Diabetes mellitus
Diabetic retinopathy
Gene therapy
Glia
Glucocorticoid receptors
Glucocorticoids
Homeostasis
Hyperglycemia
Inflammation
Literature reviews
Medicine
Medicine & Public Health
Microvasculature
Neurodegeneration
Ophthalmology
Retina
Retinopathy
Review Article
Side effects
Therapeutic applications
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Summary: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.
ISSN:0721-832X
1435-702X
DOI:10.1007/s00417-019-04521-w