Patients with inflammatory diseases, including allergy, asthma, and autoimmune disorders are often prescribed glucocorticoids; however, a subset of patients develop secondary glaucoma in response to treatment and must stop use of these beneficial steroid hormones.
In this issue of the Journal of Clinical Investigation, Val Sheffield and colleagues at the University of Iowa developed a murine model of glucocorticoid-induced glaucoma in which topical administration of 0.1% dexamethasone to the eye produces clinical hallmarks of human disease, including a substantial increase in intraocular pressure (IOP), functional and structural loss of retinal ganglion cells, axonal degeneration, and ECM alterations within cells of the trabecular meshwork (TM).
Evaluation of human TM cells revealed chronic ER stress in response to dexamethasone.
Moreover, increased IOP in response to dexamethasone was prevented in animals lacking the ER stress-associated transcription factor CHOP or treated with the chemical chaperone sodium 4-phenylbutyrate.
These results indicate that ER stress contributes to the etiology of glucocorticoid-induced glaucoma and suggest that reducing ER stress has therapeutic potential for relieving elevated IOP.