1 Department of Cell Biology and Immunology, University of North Texas Health Science Center , Fort Worth, Texas.
J Ocul Pharmacol Ther. 2014 Mar-Apr;30(2-3):121-7. doi: 10.1089/jop.2013.0239. Epub 2014 Feb 7.
Glucocorticoid (GC)-induced ocular hypertension (OHT) is a serious side effect of GC therapy in susceptible individuals. This OHT is due to increased aqueous humor (AH) outflow resistance in the trabecular meshwork (TM) caused by GC-mediated changes in TM structure and function. GCs may also play a role in the development of primary open-angle glaucoma (POAG). Elevated cortisol levels in the AH or enhanced GC sensitivity may be one of the reasons for elevated intraocular pressure in POAG patients. The GC OHT responder population is at greater risk of developing POAG compared with non-responders. We recently have gained insight into the molecular mechanisms responsible for this differential GC responsiveness, which is attributed to differences in GC receptor isoform expression in the TM. This article summarizes current knowledge on alternative GC receptor splicing to generate GC receptor alpha (GRα) and GRβ and their roles in the regulation of GC responsiveness in normal and glaucoma TM.
糖皮质激素（GC）诱导的眼压升高（OHT）是 GC 治疗在易感个体中产生的严重副作用。这种 OHT 是由于 GC 介导的 TM 结构和功能改变导致房水流出阻力增加所致。GC 也可能在原发性开角型青光眼（POAG）的发展中起作用。房水中皮质醇水平升高或 GC 敏感性增强可能是 POAG 患者眼压升高的原因之一。与非应答者相比，GC OHT 应答者人群发生 POAG 的风险更高。我们最近深入了解了导致这种 GC 反应性差异的分子机制，这归因于 TM 中 GC 受体同工型表达的差异。本文总结了目前关于产生 GC 受体α（GRα）和 GRβ的替代 GC 受体剪接的知识，以及它们在正常和青光眼 TM 中调节 GC 反应性的作用。
