Impact of aromatase absence on murine intraocular pressure and retinal ganglion cells.

Impact of aromatase absence on murine intraocular pressure and retinal ganglion cells.
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DOI:
10.1038/s41598-018-21475-x
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发表时间:
2018-02-19
期刊:
影响因子:
4.6
通讯作者:
Sullivan DA
Sullivan DA
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Chen X;Liu Y;Zhang Y;Kam WR;Pasquale LR;Sullivan DA

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我们假设芳香化酶,一种调节雌激素产生的酶,在眼压(IOP)和视网膜神经节细胞(RGCs)的控制中起着重要作用。为了验证我们的假设,我们研究了芳香化酶缺失对雄性和雌性小鼠的影响,它完全消除了雌激素的合成。研究对象为成年、年龄匹配的野生型(WT)和芳香酶敲除(ArKO)小鼠。在12周龄和24周龄有意识小鼠的双眼中以蒙面方式测量IOP。取视网膜,用共聚焦显微镜进行RGC计数。12周龄和24周龄雌性ArKO小鼠的IOP水平均显著高于年龄和性别匹配的WT对照组。12周龄小鼠IOP平均升高7.9%,24周龄小鼠IOP平均升高19.7%。这些变化伴随着ArKO雌性小鼠的RGC数量在12周和24周时分别相对于对照组显著减少9%和7%。相反,芳香化酶缺乏不会导致雄性小鼠眼压升高。与年龄和性别匹配的WT对照组相比,12周大的雄性ArKO小鼠的RGC计数明显减少,而24周大的雄性ArKO小鼠则没有。总的来说,我们的研究结果表明,女性的芳香酶抑制与IOP升高和RGC计数减少有关。
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.
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