Pro-Homeostatic Effects of Estrogen on Intraocular Pressure and the Trabecular Meshwork.

Abstract

PURPOSE: Elevated intraocular pressure (IOP) results from the dysregulation of aqueous humor outflow through the mechanoresponsive trabecular meshwork (TM). Evidence suggests that low estrogen (E2) and high TGF&#x3b2;2 levels are risk factors for elevated IOP and primary open-angle glaucoma. We sought to examine whether E2 signaling is involved in TM regulation of IOP homeostasis. METHODS: IOP and central cornea thickness were measured in male and female Esr1-/- mice and wild-type littermate controls from 3 to 12 months of age. Primary human TM cells (n = 10, 6 females and 4 males) were treated with TGF&#x3b2;2 and/or E2 in the presence/absence of cyclic mechanical stretch (CMS) for 24 hours. Expression differences of 17 TGF&#x3b2;2-responsive genes were assayed by quantitative RT-PCR. RESULTS: Higher IOP was observed in Esr1-/- females compared to wild-type females (P < 0.05). Treatment with TGF&#x3b2;2 and/or E2 significantly affected the expression of 10 genes (BMP1, CCN2, FST, GREM1, LAMC1, NFATC1, SERPINE1, SMAD2, SMAD3, and VCAN), with CMS exacerbating the effects of TGF&#x3b2;2. The addition of E2 ameliorated the effects of TGF&#x3b2;2 on two genes (NFATC1 and SMAD2) under static conditions and five genes (BMP1, FST, LAMC1, NFATC1, and SMAD2) under CMS. CONCLUSIONS: These findings suggest that estrogen signaling promotes homeostatic TM regulation of IOP.