Review
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Role of Glucocorticoids and Glucocorticoid Receptors in Glaucoma Pathogenesis
Version 1
: Received: 4 September 2023 / Approved: 5 September 2023 / Online: 6 September 2023 (02:34:47 CEST)
A peer-reviewed article of this Preprint also exists.
Patel, P.D.; Kodati, B.; Clark, A.F. Role of Glucocorticoids and Glucocorticoid Receptors in Glaucoma Pathogenesis. Cells 2023, 12, 2452. Patel, P.D.; Kodati, B.; Clark, A.F. Role of Glucocorticoids and Glucocorticoid Receptors in Glaucoma Pathogenesis. Cells 2023, 12, 2452.
Abstract
Abstract: The glucocorticoid receptor (GR), including both alternative spliced isoforms (GRa and GRb), 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 lower expression of GRb, 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. Increased expression of GRb can block GC-induced pathogenic changes in TM cells and reverse GC-OHT in mice. Endogenous expression of GRb in the TM may relate to differences in the development of GC-OHT among 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.
Keywords
glucocorticoid receptor; glaucoma; animal models; anti-inflammatory steroids; primary open-angle glaucoma; steroid glaucoma; ocular hypertension; eye
Subject
Medicine and Pharmacology, Ophthalmology
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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