Lymphocyte Sensitivity to Glucocorticoids

BenEzra, David; Ticho, U; Sachs, Uriel

doi:10.1016/0002-9394(76)90062-3

Cited by 11 publications

(1 citation statement)

References 12 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The hypothesis is further supported by the findings that individuals who are steroid-responders have a higher risk of developing POAG [9,10]. However, other labs were not able to replicate elevated plasma cortisol or altered cortisol sensitivity in POAG patients [53,54], which made the association between endogenous cortisol and elevated IOP less clear. It should be noted that serum levels of cortisol vary widely depending on the time of day as well as the varying levels of stress in individuals, which may well explain the different findings among these studies.…”

Section: Role Of Endogenous Cortisol and Cortisol Metabolism In Poagmentioning

confidence: 92%

Role of Glucocorticoids and Glucocorticoid Receptors in Glaucoma Pathogenesis

Patel,

Kodati,

Clark

2023

Cells

View full text Add to dashboard Cite

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.

show abstract

Section: Role Of Endogenous Cortisol and Cortisol Metabolism In Poagmentioning

confidence: 92%