Effects of Age and Ovariectomy on Visual Function in Experimental Glaucoma

Abstract

Purpose : Recent evidence states that a woman’s risk for developing glaucoma increases up to 3.5-fold if she undergoes early menopause (Hulsman et al. 2001 & Vajaranant et al. 2012). We hypothesize that estrogen deficiency leads to a greater degree of visual impairment in females exposed to ocular hypertension (OHT), due to estrogen effects on ocular connective tissue biomechanics. We investigated the susceptibility of pre- and post-menopausal rats to develop progressive visual dysfunction in an experimental model of glaucomatous OHT.

Methods : Young (3 month) and aged (10 month) female Brown-Norway rats were divided into pre- and post-menopausal cohorts. Menopause was induced surgically via ovariectomy (OVX), creating 4 cohorts: young non-OVX (n=4), young OVX (n=4), aged non-OVX (n=4) and aged OVX (n=3). Two weeks after OVX, hypertonic saline was injected unilaterally into the epsicleral venous plexus to induce OHT (Morrison model). Intraocular pressure (IOP) was measured weekly (Tonolab) to determine the IOP insult (mmHg day) on the eyes. After 8 weeks we assessed retinal ganglion cell (RGC) function via pattern electroretinography (pERG), visual acuity via optokinetic tracking (OKT), and optic nerve head (ONH) anatomy via optical coherence tomography (OCT). A two factor MANCOVA, with IOP insult as the covariate, was used to compare the effects of OVX and age.

Results : In this preliminary study, IOP insult had a significant influence on pERG and visual acuity outcomes (p=0.002). Within each age group, OVX rats tended to have worse pERG and OKT outcomes vs. non-OVX rats; however, with our limited sample size, we did not reach statistical significance for effects of OVX status or age on pERG and OKT. Interestingly, OCT revealed differential changes between young and aged cohorts in ONH anatomy after OHT (Figure).

Conclusions : Although limited by sample size in this initial study, trends are consistent with clinical observations of estrogen being neuroprotective in glaucoma, indicating the utility of further studies with this rat model. Ongoing work will add animals and outcome measures (e.g. retinal nerve fiber layer thickness by OCT) and characterizing biomechanical properties.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

 

Figure: Representative images of the optic nerve head of OHT eyes in young (left) and aged (right) rats. Each rat had an average IOP of 35-45 mmHg over 8 weeks. Compared to aged animals, young rats had minor cupping.