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Andrew Feola, Joseph Sherwood, Darryl R Overby, Machelle T Pardue, C Ross Ethier; Impact of Estrogen Deficiency on Outflow Facility and Ocular Biomechanics in Rats. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1217.
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Recent studies suggest that an estrogen deficiency may increase the risk of developing glaucoma. Early menopause, mutations in estrogen receptors, and mutations along the estrogen metabolic pathway are all associated with an increased risk for glaucoma. While it is unclear what role estrogen plays in developing this disease, estrogen therapy has been shown to modestly lower intraocular pressure (IOP) in postmenopausal women. We hypothesize that an estrogen deficiency alters the outflow pathway and ocular tissue biomechanics, thus impacting IOP and ocular deformation. These changes may lead to retinal ganglion cell axon damage and loss, which may contribute to the etiology of glaucoma. To test this hypothesis, we used the iPerfusion system to examine the impact of menopause on outflow facility and on ocular compliance, a measure of ocular connective tissue biomechanics
Female Brown-Norway rats (3-4 months of age) were randomly assigned to either pre- or post-menopausal groups. We induced menopause surgically by ovariectomy (OVX), while the pre-menopausal group underwent a sham surgery (Sham). Eight weeks after surgery, eyes were enucleated and perfused at eight pressure levels to determine outflow facility and ocular compliance in Sham (n=7) and OVX (n=7) rats. We determined outflow facility using an established relationship between pressure and flow and calculated ocular compliance based on ocular pressure and volume changes. Both parameters were determined at a reference pressure of 20 mmHg. We used a t-test to compare outflow facility and ocular compliance between Sham and OVX animals (p<0.05).
Average outflow facility was 42% lower [95% CI: 21%, 56%] in OVX vs. Sham animals (p=0.015, Figure 1). Ocular compliance was 10% higher [95% CI: 2%, 18%] in the OVX vs. Sham animals (p=0.034, Figure 1).
Supporting our hypothesis, an estrogen deficiency both lowered outflow facility and reduced the stiffness of ocular connective tissues, leading to more tissue deformation at a given IOP. Future studies will explore potential mechanisms by which estrogen influences outflow facility and ocular biomechanical properties.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
Figure 1: The impact of menopause on outflow facility (left) and ocular compliance (right) in Sham and OVX rats.
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