Menopause Worsens Visual Function Following Optic Nerve Crush

Abstract

Purpose : Glaucoma is the leading cause of irreversible blindness worldwide, and women represent roughly 60% of the affected population (Quigley et al. 2006). Studies suggests that early menopause, mutations in estrogen receptors, and mutations along the estrogen metabolic pathway were associated with developing glaucoma (Vajaranant and Pasquale 2012). Recently, we found that menopause exacerbated visual dysfunction in an ocular hypertension model of glaucoma (Feola et al. 2019). Here, we aimed to investigate if menopause exacerbated visual function in a model of direct retinal ganglion cell (RGC) damage via optic nerve crush (ONC).

Methods : Female Long Evans rats (n=12, 9-10 months) were evenly divided into pre- and post-menopausal groups. Menopause was induced using the well-established ovariectomy (OVX) model, while pre-menopausal animals underwent a Sham surgery (SH). Eight weeks after surgery, animals underwent baseline optomotor response to assess visual acuity using spatial frequency thresholds. Afterwards, one eye underwent ONC while the contralateral eye was an internal control. Visual function was assessed at 4, 8, and 12 weeks post-ONC. At 12 weeks, retinal function via electroretinography using a dark-adapted protocol (-4 to 2 log cd-s/m²) and retinal nerve fiber layer (RNFL) thickness via optical coherence tomography was measured.

Results : We observed a significant decline in visual acuity after ONC (p<0.001). However, compared to Sham animals, menopausal animals had 27% lower visual acuity 12 weeks after ONC (Figure; p=0.01). We observed no differences in a-wave, b-wave, or oscillatory potentials. We observed RNFL thinning at 12 weeks in both groups (p=0.009).

Conclusions : These results support that menopause leads to worse visual function in models of RGC damage, and agrees with our previous work using ocular hypertension. This model is independent of intraocular pressure demonstrating that direct damage to RGCs results in worse visual function after menopause. Combined, these data suggest that menopausal status plays a role in RGC survival after injury.

This is a 2020 ARVO Annual Meeting abstract.

 

Figure: Menopausal (OVX) and Sham (SH) animals had worse spatial frequency (Left: mean ± S.E.M.) after ONC. Spatial frequency thresholds after ONC were lower in OVX compared SH animals (*p<0.05; ***p<0.001). RNFL was thinner (p=0.009) after ONC (Right: box plot) but no differences were found between groups.