Schepens Eye Research Institute, Massachusetts Eye and Ear, and Department of Ophthalmology, Harvard Medical School, Boston, MA, USA.
Zhongnan Hospital, Wuhan University, Wuhan, China.
Sci Rep. 2018 Feb 19;8(1):3280. doi: 10.1038/s41598-018-21475-x.
We hypothesize that aromatase, an enzyme that regulates estrogen production, plays a significant role in the control of intraocular pressure (IOP) and retinal ganglion cells (RGCs). To begin to test our hypothesis, we examined the impact of aromatase absence, which completely eliminates estrogen synthesis, in male and female mice. Studies were performed with adult, age-matched wild type (WT) and aromatase knockout (ArKO) mice. IOP was measured in a masked fashion in both eyes of conscious mice at 12 and 24 weeks of age. Retinas were obtained and processed for RGC counting with a confocal microscope. IOP levels in both 12- and 24-week old female ArKO mice were significantly higher than those of age- and sex-matched WT controls. The mean increase in IOP was 7.9% in the 12-week-, and 19.7% in the 24-week-old mice, respectively. These changes were accompanied by significant 9% and 7% decreases in RGC numbers in the ArKO female mice, relative to controls, at 12- and 24-weeks, respectively. In contrast, aromatase deficiency did not lead to an increased IOP in male mice. There was a significant reduction in RGC counts in the 12-, but not 24-, week-old male ArKO mice, as compared to their age- and sex-matched WT controls. Overall, our findings show that aromatase inhibition in females is associated with elevated IOP and reduced RGC counts.
我们假设,一种调节雌激素生成的酶——芳香酶,在眼压(IOP)和视网膜神经节细胞(RGCs)的控制中发挥着重要作用。为了开始验证我们的假设,我们研究了芳香酶缺失(完全消除雌激素合成)对雄性和雌性小鼠的影响。该研究采用成年、年龄匹配的野生型(WT)和芳香酶敲除(ArKO)小鼠进行。在清醒的小鼠中,以盲法测量双眼的 IOP,分别在 12 周和 24 周龄时进行。获取视网膜并使用共聚焦显微镜进行 RGC 计数处理。12 周和 24 周龄的雌性 ArKO 小鼠的 IOP 水平明显高于年龄和性别匹配的 WT 对照组。12 周龄时 IOP 平均升高 7.9%,24 周龄时升高 19.7%。这些变化伴随着 12 周和 24 周龄的雌性 ArKO 小鼠的 RGC 数量分别相对对照组下降 9%和 7%。相比之下,芳香酶缺乏不会导致雄性小鼠的 IOP 升高。与年龄和性别匹配的 WT 对照组相比,12 周龄的雄性 ArKO 小鼠的 RGC 计数显著减少,但 24 周龄时没有减少。总的来说,我们的研究结果表明,雌性的芳香酶抑制与眼压升高和 RGC 数量减少有关。