Abstract
Purpose :
We hypothesize that an early estrogen deficiency accelerates the aging of the optic nerve and predisposes to glaucomatous damage. To begin to test our hypotheses, we sought to determine whether estrogen deprivation is associated with elevated intraocular pressure (IOP) and retinal ganglion cell (RGC) loss in male and female mice.
Methods :
We obtained breeding pairs of C57BL/6J - aromatase knockout (ArKO) heterozygous mice (Dr. Nabil J. Alkayed; Oregon Health & Science University, Portland, OR) to generate homozygous ArKO mice and their wildtype (WT) controls. The homozygous ArKO mice harbored a targeted disruption of exon IX in the cyp19 gene and possess no aromatase activity. Aromatase catalyzes the conversion of androstenedione to estrone and the conversion of testosterone to estradiol. At 12 and 24 weeks of age, we measured in a masked fashion the IOP (n = 6 consecutive IOP measurements/value, 3 values/eye/day, 2 consecutive days) in the left and right eyes of conscious mice (n = 7-8/group/sex). Animals were then sacrificed and retinas were flat mounted and stained with Brn3a antibodies to facilitate RGC counting using confocal microscopy. Unpaired t-tests were used for statistical analyses.
Results :
The IOP levels in both 12- and 24-week old female ArKO mice were significantly (p < 0.0001) higher than those of age- and sex-matched WT controls. The mean increase in IOP ranged from 1.1 mmHg (7.9%) in the 12-week-, to 2.6 mmHg (19.7%) in the 24-week-old mice, respectively. These changes were accompanied by significant (p < 0.05, 12-week; p < 0.05, 24-week) decreases in RGC numbers in the ArKO female mice, relative to controls. In contrast, estrogen deficiency did not lead to an increased IOP in male mice. There was, however, a significant reduction in RGC counts in the 12- (p < 0.05), but not 24- (p = 0.90) week-old male ArKO mice, as compared to their age- and sex-matched WT controls.
Conclusions :
Our results support our hypothesis that estrogen deprivation promotes the development of glaucoma.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.