Sulaiman Rania S, Kadmiel Mahita, Cidlowski John A
Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institute of Health, Department of Health and Human Services, Research Triangle Park, NC, USA.
Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institute of Health, Department of Health and Human Services, Research Triangle Park, NC, USA.
Steroids. 2018 May;133:60-66. doi: 10.1016/j.steroids.2017.11.002. Epub 2017 Nov 10.
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.
糖皮质激素(GCs)是重要的类固醇激素,调节几乎所有生理系统中的众多代谢和稳态功能。合成糖皮质激素是治疗各种疾病(包括自身免疫性、过敏性和炎症性疾病)最常用的处方药之一。糖皮质激素主要因其通过核受体糖皮质激素受体(GR)介导的信号转导所产生的强大抗炎和免疫抑制活性而被使用。新出现的证据表明,糖皮质激素的各种生理和治疗作用具有组织、细胞和性别特异性,这表明糖皮质激素的作用比以前预期的更为复杂。虽然几种合成糖皮质激素在眼科临床中被广泛用于治疗多种眼部疾病,但对于糖皮质激素在眼的不同层中的信号传导机制仍知之甚少。GR已被证明在眼的不同细胞类型(如角膜、晶状体和视网膜)中表达,这表明GR信号在这些眼部组织的生理学中具有重要作用。在本综述中,我们提供了过去5年报道的体外和体内研究的最新发现,旨在了解GR信号在眼中的具体作用。研究糖皮质激素在眼中的生理作用的进展对于制定具有强大抗炎潜力同时将副作用降至最低的优化和靶向GC疗法至关重要。