Decreased Response of Plasma Cortisol to Intravenous Metyrapone in Ocular Hypertension and Primary Open-Angle Glaucoma

Schwartz, Bernard; Wysocki, Alice; Qi, Youlin

doi:10.1097/01.ijg.0000185613.56168.9d

Cited by 9 publications

(3 citation statements)

References 27 publications

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“…This proposal is based on the findings of elevated plasma [41][42][43][44][45] and aqueous humor [41,45] cortisol in POAG patients. There also are reports of altered cortisol responses in POAG patients [46][47][48][49][50]. In addition, Southren and colleagues reported aberrant cortisol metabolism in POAG patients [51,52].…”

Section: Role Of Endogenous Cortisol and Cortisol Metabolism In Poagmentioning

confidence: 99%

Role of Glucocorticoids and Glucocorticoid Receptors in Glaucoma Pathogenesis

Patel,

Kodati,

Clark

2023

Cells

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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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Section: Role Of Endogenous Cortisol and Cortisol Metabolism In Poagmentioning

confidence: 99%

Role of Glucocorticoids and Glucocorticoid Receptors in Glaucoma Pathogenesis

Patel,

Kodati,

Clark

2023

Cells

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“…At present, aspects related to studies on "endocrine homeostasis" in post-barrier membrane of an eye at both norm and pathology are the subject of a wide discussion in ophthalmology. The available publications are not numerous; furthermore, they are of a rather statement-ofthe-fact character [Southren A. et al, 1976;Floman N., Zor U., 1977;Kasavina B. et al, 1977;Weinstein B. et al, 1983;Stone R., Wilson C., 1984;Stojek A. et al, 1991;Chiquet C., Denis P., 2004;Burch J. et al, 2005;Pleyer U. et al, 2005;Schwartz B. et al, 2005;Vessey K. et al, 2005]. In particular, there are reports discussing the possibility of cortisol local synthesis in eye membranes.…”

Section: The Role Of Cortisol In Pathogenesis Of Anterior Open-angle mentioning

confidence: 99%

Modern Aspects of Glaucoma Pathogenesis Local Factors for Development of Primary Open-Angle Glaucoma Associated with Impairment of Secretory Functions of the Eye Membranes

Zilfyan¹

2013

Glaucoma - Basic and Clinical Aspects

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2. Secretory-mediatory hormone-dependent functions of eye membranes in the mechanisms of glaucoma development 2.1. The role of transforming growth factor β-2 (TgF β-2), insulin-like growth factor-1 (IgF-1) and Е 2 prostaglandins (PgE 2) in pathogenesis of primary open-angle glaucoma Nowadays the role of TGF β produced in post-barrier membranes of an eye is considered to be of no less importance for realization of processes ensuring the drainage function of the eye anterior chamber-associated immune deviation (ACAID)

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“…8 Thirty-three of these subjects (20 normals and 13 OH plus POAG) in this study were previously studied for their response of plasma cortisol levels to intravenous metyrapone. 9 For all subjects, single optic disc photographs were obtained with the Zeiss telecentric fundus camera (Zeiss-Dublin, CA). Areas of pallor and cupping were determined as a percentage of the area of the disc by the use of transparent templates in conjunction with stereophotographic observation 10 using simultaneous stereophotographs obtained with the Donaldson fundus camera.…”

Section: Subjectsmentioning

confidence: 99%