The Effects of Glucocorticoids on Trabecular Meshwork and its Role in Glaucoma

Abstract

Primary Open-Angle Glaucoma (POAG), an optic neuropathy that is a leading cause of irreversible blindness, has been studied extensively in hopes of better understanding its underlying mechanism. Glucocorticoids (GC) are commonly used to treat inflammatory ocular conditions but are also known to increase the risk of glaucoma by raising Intraocular Pressure (IOP) in susceptible individuals, leading to steroid-induced glaucoma. Based on clinical studies as well as molecular experiments, steroid-induced glaucoma and POAG show many similarities, including a common underlying mechanism of IOP elevation. Studying steroid-induced glaucoma can reveal more about the pathways underlying decreased outflow of aqueous humor and POAG. GCs have been shown to cause numerous structural changes in the Trabecular Meshwork (TM), including thickening of trabecular beams, activation of TM cells and increased deposition of extracellular material. GCs also upregulate the expression of MYOC (myocilin) in human TM, a gene whose mutation is linked to 10% of juvenile glaucoma cases. Other studies demonstrate that GCs downregulate PLAT, which codes for tissue Plasminogen Activator (tPA) and decrease Matrix Metalloproteinase (MMP) gene expression. In addition, tPA administration has been shown to prevent GC-induced IOP elevation in sheep eyes. The present review demonstrates some of the important interactions between GCs and the TM that can lead to novel therapeutic measures in the setting of steroid-induced glaucoma as well as POAG.