Menopause alters Ocular Biomechanics and Increases Visual Impairment in a Rat Model of Glaucoma

Abstract

Purpose : Recent studies suggest that menopause or estrogen receptor mutations modulate the risk for glaucoma. Ocular biomechanical properties influence mechanical loads at the optic nerve head and may contribute to loss of retinal ganglion cells (RGC). Estrogen is known to alter biomechanical properties in other tissues; therefore, we hypothesize that an estrogen deficiency contributes to the etiology of glaucoma by altering ocular tissue biomechanics. Here, we examined the impact of menopause on ocular compliance in rats, a measure of corneoscleral biomechanical properties. We then assessed the effect of menopause on visual function in the established Morrison ocular hypertension (OHT) model.

Methods : Female Brown-Norway rats (3-4 months) were randomly assigned to pre- or post-menopausal groups. Menopause was induced surgically by ovariectomy (OVX). We measured ocular compliance in non-OVX (n=8) and OVX (n=11) rats using the iPerfusion system. In separate cohorts of non-OVX (n=6-8) and OVX (n=8-9) rats we induced OHT unilaterally via injection of hypertonic saline to the episcleral venous plexus. OHT was confirmed by biweekly intraocular pressure measurements (Tonolab, Icare). We assessed spatial frequency and contrast sensitivity by optokinetic tracking, and RGC function by pattern electroretinogram. Visual function was assessed longitudinally: at baseline (pre-OHT), 4, and 8 weeks post-OHT. Ocular compliance data was analyzed using a Mann-Whitney test, while visual function data was analyzed by ANOVA to assess the impact of OHT, OVX, and time.

Results : Ocular compliance was 11% higher in post-menopausal vs. pre-menopausal rats (p=0.0099, Figure). Spatial frequency thresholds decreased due to OVX (p=0.008), OHT (p<0.001), and over time in OHT eyes (p<0.001, Figure). Contrast sensitivity showed similar decline due to OHT (p<0.001) and over time (p<0.001). RGC function showed a significant decline due to OVX (p=0.035), OHT (p=0.021) and over time (p=0.016).

Conclusions : Supporting our hypothesis, estrogen deficiency altered ocular biomechanical properties (increased ocular compliance) and was associated with poorer visual outcomes in OHT (lower spatial frequency and RGC function). In the future, we will explore estrogen as a neuroprotective intervention in this experimental rat model of glaucoma.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

 

The impact of menopause (OVX) on ocular compliance (left) and visual acuity (right) after OHT in rats.