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Review
. 2018 May;133:60-66.
doi: 10.1016/j.steroids.2017.11.002. Epub 2017 Nov 10.

Glucocorticoid Receptor Signaling in the Eye

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Free PMC article
Review

Glucocorticoid Receptor Signaling in the Eye

Rania S Sulaiman et al. Steroids. .
Free PMC article

Abstract

Glucocorticoids (GCs) are essential steroid hormones that regulate numerous metabolic and homeostatic functions in almost all physiological systems. Synthetic glucocorticoids are among the most commonly prescribed drugs for the treatment of various conditions including autoimmune, allergic and inflammatory diseases. Glucocorticoids are mainly used for their potent anti-inflammatory and immunosuppressive activities mediated through signal transduction by their nuclear receptor, the glucocorticoid receptor (GR). Emerging evidence showing that diverse physiological and therapeutic actions of glucocorticoids are tissue-, cell-, and sex-specific, suggests more complex actions of glucocorticoids than previously anticipated. While several synthetic glucocorticoids are widely used in the ophthalmology clinic for the treatment of several ocular diseases, little is yet known about the mechanism of glucocorticoid signaling in different layers of the eye. GR has been shown to be expressed in different cell types of the eye such as cornea, lens, and retina, suggesting an important role of GR signaling in the physiology of these ocular tissues. In this review, we provide an update on the recent findings from in vitro and in vivo studies reported in the last 5 years that aim at understanding the role of GR signaling specifically in the eye. Advances in studying the physiological effects of glucocorticoids in the eye are vital for the elaboration of optimized and targeted GC therapies with potent anti-inflammatory potential while minimizing adverse effects.

Keywords: Eye; Glucocorticoid; Glucocorticoid receptor; Glucocorticoid signaling; Ocular diseases.

Figures

Figure 1
Figure 1
Glucocorticoid receptor (GR) regulation and signaling. (A) Schematic representation of regulation of glucocorticoid (GC) levels by the hypothalamic-pituitary adrenal (HPA) axis, and the regulation of the conversion between the biologically active form of GCs, cortisol and the inactive form, cortisone, by 11β-hydroxysteroid dehydrogenase type 1 and type 2. (B) Representation of GR structure containing N-terminal transactivation domain (NTD), a central DNA binding domain (DBD), a flexible hinge region (H) and a C-terminal ligand binding domain (LBD). (C) GR isoforms generated by alternative splicing. (D) GR signaling following the binding of GCs to the cytoplasmic GR, which then undergoes conformational changes that result in the dissociation from accessory proteins and translocation to the nucleus. In the nucleus, GR regulates the expression of target genes by multiple ways such as a direct binding to glucocorticoid-response elements (GRE) and activation of glucocorticoid-induced leucine zipper (GILZ) transcription factor.
Figure 2
Figure 2
Role of glucocorticoids in the eye. Schematic representation of major layers of the eye, demonstrated roles of glucocorticoids (black text), and reported adverse effects (red text).

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