Does estrogen deficiency cause lacrimal gland inflammation and aqueous-deficient dry eye in mice?

Does estrogen deficiency cause lacrimal gland inflammation and aqueous-deficient dry eye in mice?
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DOI:
10.1016/j.exer.2014.07.017
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发表时间:
2014-10-01
影响因子:
3.4
通讯作者:
Sullivan, David A.
Sullivan, David A.
中科院分区:
医学3区
文献类型:
--
作者:
Darabad, Raheleh Rahimi;Suzuki, Tomo;Sullivan, David A.

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研究人员提出,雌激素缺乏会导致类似干燥综合征(SjS)的泪腺炎症、水性泪液缺乏和干眼。本研究的目的是确定这一建议是否正确。泪腺取自成年、年龄匹配野生型(WT)和芳香酶敲除(ArKO)小鼠,这些小鼠完全消除了雌激素的合成。还从自身免疫MRL/Mp-lprflpr (MRL/lpr)小鼠中获得组织作为炎症对照。测量WT和ArKO小鼠的泪液体积,并对腺体进行分子生物学和组织学评价。我们的研究结果表明,雌激素缺乏不会导致泪道组织的sjs样炎症或缺水干眼。雌雄ArKO小鼠泪腺炎症通路相关基因均未出现上调。这种炎症活动在自身免疫MRL/Ipr组织中很突出。我们还发现雌激素缺乏小鼠的泪腺组织切片中没有炎症的证据,与WT对照组相比,ArKO雄性的泪液量实际上增加了。有趣的是,我们的研究确实表明,雌激素的缺乏会影响数千种泪腺基因的表达,而且这种影响是性别和基因型特异性的。我们的研究结果表明,雌激素缺乏不是sjs样泪腺炎症或小鼠缺水性干眼症发展的危险因素。(C) 2014 Elsevier Ltd.版权所有。
Researchers have proposed that estrogen deficiency will lead to a Sjogren's syndrome (SjS)-like lacrimal gland inflammation, aqueous tear deficiency and dry eye. The purpose of this study was to determine whether this proposal is correct. Lacrimal glands were obtained from adult, age-matched wild type (WT) and aromatase knockout (ArKO) mice, in which estrogen synthesis is completely eliminated. Tissues were also obtained from autoimmune MRL/Mp-lprflpr (MRL/lpr) mice as inflammation controls. Tear volumes in WT and ArKO mice were measured and glands were processed for molecular biological and histological evaluation. Our results demonstrate that estrogen absence does not lead to a SjS-like inflammation in lacrimal tissue or to an aqueous-deficient dry eye. There was no upregulation of genes associated with inflammatory pathways in lacrimal glands of male or female ArKO mice. Such inflammatory activity was prominent in autoimmune MRL/Ipr tissues. We also found no evidence of inflammation in lacrimal gland tissue sections of estrogen-deficient mice, and tear volumes of ArKO males were actually increased as compared to those WT controls. Interestingly, our study did show that estrogen absence influences the expression of thousands of lacrimal gland genes, and that this impact is sex- and genotype-specific. Our findings demonstrate that estrogen absence is not a risk factor for the development of SjS-like lacrimal gland inflammation or for aqueous-deficient dry eye in mice. (C) 2014 Elsevier Ltd. All rights reserved.