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

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 TGFβ2 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 TGFβ2 and/or E2 in the presence/absence of cyclic mechanical stretch (CMS) for 24 hours. Expression differences of 17 TGFβ2-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 TGFβ2 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 TGFβ2. The addition of E2 ameliorated the effects of TGFβ2 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.