Menopause exacerbates visual dysfunction in experimental glaucoma

• Type of Material: Article
• Authors: Andrew Feola, Emory University; Jieming Fu, Atlanta VA Healthcare System; Rachael Allen, Atlanta VA Healthcare System; Victoria Yang, Atlanta VA Healthcare System; Ian C. Campbell, Atlanta VA Healthcare System; Amy Ottensmeyer, Emory University; Christopher Ethier, Emory University; Machelle Pardue, Emory University
• Language: English
• Date: 2019-09-01
• Publisher: Academic Press Ltd. - Elsevier Science Ltd.
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2019 Published by Elsevier Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.exer.2019.107706
• Title of Journal or Parent Work: Experimental Eye Research
• Volume: 186
• Start Page: 107706
• End Page: 107706
• Grant/Funding Information: This work was partially funded by the RR&D Service Career Development Award (RX002342; AJF), RR&D Service Career Development Award (RX002928; RA), RR&D Service Research Career Scientist Award (C9257; MTP), and the Georgia Research Alliance (CRE).
• Keywords: Glaucoma; Life Sciences & Biomedicine; Intraocular pressure; Visual function; Retinal degeneration; Estrogen receptor beta; Menopause; Thickness; Optical coherence tomography; Blood pressure; Age; Science & Technology; Estrogen; Open-angle glaucoma; Contrast sensitivity; Ophthalmology; Nerve fiber layer
• Research Categories: Biology, Neuroscience; Engineering, Biomedical; Health Sciences, Opthamology

Abstract

Glaucoma is the leading cause of irreversible blindness worldwide. Recently, estrogen deficiencies caused by early menopause, alterations in estrogen signaling via mutations in estrogen receptors, and polymorphisms along estrogen metabolic pathways have all been linked to an increased risk of developing glaucoma. Here, we examined how menopause and age impact visual function and retinal structure in an experimental model of glaucoma. Young (3–4 months) and aged (9–10 months) female Brown Norway rats were divided into pre- and post-menopausal cohorts by surgically inducing menopause via ovariectomy (OVX). After six weeks, ocular hypertension (OHT) was induced unilaterally for a period of eight weeks. Four cohorts were successfully followed to eight weeks: young sham (n = 8), young OVX (n = 9), aged sham (n = 10), and aged OVX (n = 11) animals. Intraocular pressure (IOP) was monitored weekly in all groups. Prior to inducing OHT (baseline) and at four and eight weeks after inducing OHT, we assessed visual acuity via the optomotor response (OMR) and retinal structure using optical coherence tomography (OCT). OHT decreased the OMR in all cohorts. We found that spatial frequency thresholds decreased by 54% in OVX animals after OHT compared to sham animals after OHT, regardless of age (p < 0.001). We also found thinning of the retinal nerve fiber layer (RNFL) and loss of total retinal thickness after induction of OHT. Aged animals had more thinning of the RNFL and loss of total retinal thickness compared to young animals (p < 0.001). Overall, OHT caused significant changes in visual function and retinal structure. Observing that OVX in young and aged animals further decreased spatial frequency thresholds after OHT suggests that an estrogen deficiency may intensify visual impairment after OHT.