Role of Glucocorticoids and Glucocorticoid Receptors in Glaucoma Pathogenesis.
Role of Glucocorticoids and Glucocorticoid Receptors in Glaucoma Pathogenesis.
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作者：
糖皮质激素受体(GR)包括两种选择性剪接异构体(GRα和GRβ)，与原发性开角型青光眼(POAG)和医源性糖皮质激素性青光眼(GIG)的发生有关。开角型青光眼是最常见的青光眼，是世界上不可逆转的视力丧失和失明的主要原因。糖皮质激素(GCs)通常用于治疗眼科和许多其他疾病/状况。长期GC治疗的一个严重副作用是医源性继发性高眼压(OHT)和OAG(即GC诱导的青光眼(GIG))，在临床和病理上类似于POAG。GC诱导的OHT是由小梁网络(TM)的病理性损伤引起的，小梁网络是一种参与调节房水流出和眼压的组织。与来自年龄匹配的对照眼的TM细胞相比，来自POAG眼的TM细胞(GTM细胞)的GRβ的表达较低，GR DNA是GC活性的主要负调节因子。因此，GTM细胞对GCs有更强的致病反应。几乎所有的POAG患者在接受GCs治疗时都会发生GC-OHT，而正常人群的GC应答率为40%。增加GRβ的表达可以阻断GC诱导的TM细胞的致病变化，并逆转GC-OHT。GRβ在TM中的内源性表达可能与正常人群中GC-OHTs的发育不同有关。许多研究表明POAG患者内源性皮质醇水平升高以及皮质醇代谢的差异，提示GCs可能参与了POAG的发生发展。有必要进行更多的研究，以更好地了解POAG和GIG的分子机制，以便开发新的疾病修正疗法，以更好地治疗这两种威胁视力的青光眼。这篇及时综述的目的是强调GIC-OHT和GIG的病理和临床特征，负责GC反应的机制，潜在的治疗选择，以及GIG与POAG的相似特征。
The glucocorticoid receptor (GR), including both alternative spliced isoforms (GRα and GRβ), has been implicated in the development of primary open-angle glaucoma (POAG) and iatrogenic glucocorticoid-induced glaucoma (GIG). POAG is the most common form of glaucoma, which is the leading cause of irreversible vision loss and blindness in the world. Glucocorticoids (GCs) are commonly used therapeutically for ocular and numerous other diseases/conditions. One serious side effect of prolonged GC therapy is the development of iatrogenic secondary ocular hypertension (OHT) and OAG (i.e., GC-induced glaucoma (GIG)) that clinically and pathologically mimics POAG. GC-induced OHT is caused by pathogenic damage to the trabecular meshwork (TM), a tissue involved in regulating aqueous humor outflow and intraocular pressure. TM cells derived from POAG eyes (GTM cells) have a lower expression of GRβ, a dominant negative regulator of GC activity, compared to TM cells from age-matched control eyes. Therefore, GTM cells have a greater pathogenic response to GCs. Almost all POAG patients develop GC-OHT when treated with GCs, in contrast to a GC responder rate of 40% in the normal population. An increased expression of GRβ can block GC-induced pathogenic changes in TM cells and reverse GC-OHT in mice. The endogenous expression of GRβ in the TM may relate to differences in the development of GC-OHT in the normal population. A number of studies have suggested increased levels of endogenous cortisol in POAG patients as well as differences in cortisol metabolism, suggesting that GCs may be involved in the development of POAG. Additional studies are warranted to better understand the molecular mechanisms involved in POAG and GIG in order to develop new disease-modifying therapies to better treat these two sight threatening forms of glaucoma. The purpose of this timely review is to highlight the pathological and clinical features of GC-OHT and GIG, mechanisms responsible for GC responsiveness, potential therapeutic options, as well as to compare the similar features of GIG with POAG.
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影响因子：
6
作者：
Deploey, Nick;Van Moortel, Laura;Rogatsky, Inez;Peelman, Frank;De Bosscher, Karolien
通讯作者：
De Bosscher, Karolien
影响因子：
3.1
作者：
Agarwal R;Gupta SK;Agarwal P;Saxena R;Agrawal SS
通讯作者：
Agrawal SS
影响因子：
2.3
作者：
Gelatt, KN;Mackay, EO
通讯作者：
Mackay, EO
影响因子：
4.4
作者：
Clark, Abbot F.
通讯作者：
Clark, Abbot F.
DOI：
10.1007/bf00407840
发表时间：
1978-01-01
期刊：
ALBRECHT VON GRAEFES ARCHIV FUR KLINISCHE UND EXPERIMENTELLE OPHTHALMOLOGIE
影响因子：
--
作者：
BONOMI, L;PERFETTI, S;TOMAZZOLI, L
通讯作者：
TOMAZZOLI, L