Treatment of glaucoma by prostaglandin agonists and beta-blockers in combination directly reduces pro-fibrotic gene expression in trabecular meshwork.

Abstract

Prostaglandin analogues (PG), beta‐blockers (BB) or their combination (PG+BB) are used primarily to reduce the intraocular pressure (IOP) pathologically associated with glaucoma. Since, fibrosis of the trabecular meshwork (TM) is a major aetiological factor in glaucoma, we studied the effect of these drugs on fibrosis‐associated gene expression in TM of primary glaucoma patients. In the present study, TM and iris of primary open‐angle (n = 32) and angle‐closure (n = 37) glaucoma patients were obtained surgically during trabeculectomy and categorized based on the type of IOP‐lowering medications use as PG, BB or PG+BB. mRNA expression of pro‐fibrotic and anti‐fibrotic genes was quantified using qPCR in these tissues. The gene expression levels of pro‐fibrotic genes were significantly lower in PG+BB as compared to other groups. These observations and underlying signalling validated in vitro in human TM cells also showed reduced fibrotic gene and protein expression levels following PG+BB treatment. In conclusion, it is observed that PG+BB combination rather than their lone use renders a reduced fibrotic status in TM. This further suggests that IOP‐lowering medications, in combination, would also modulate fibrosis‐associated molecular changes in the TM, which may be beneficial for maintaining aqueous out‐flow mechanisms over the clinical treatment duration.