Sex, sex steroids and dry eye syndromes

眼前泪膜在维持眼表完整性、防止眼内炎性反应、预防眼内炎性反应、预防眼内炎性反应中起着重要作用。 微生物挑战和保持视力。泪膜功能障碍反过来可能严重影响眼睛 并导致角膜干燥、溃疡和穿孔， 疾病，以及明显的视力障碍和失明。无数人患有泪膜疾病， 其被称为干眼综合征，并被分为两种主要类型：水分缺乏型和 蒸发水缺乏性干眼症是由于泪腺分泌的泪液减少。一个 例如干燥综合征，一种常见的自身免疫性疾病，主要折磨女性， 泪腺蒸发性干眼症通常由睑板腺功能障碍引起，并且可能是一种慢性炎症。 更年期干眼症的主要原因是使用雌激素替代疗法和衰老。远程 这项拨款申请的目的是测试我们的假设：（1）性类固醇在 眼表和附属器的生理调节以及泪膜的产生;和 (2)性、性类固醇激素，特别是雄激素缺乏，是 水缺乏和蒸发性干眼综合征的发病机制。实验程序 包括小鼠模型、全基因组微阵列（例如基因芯片）、实时PCR、原位杂交 细胞培养、免疫测定、2D凝胶、MALDI/质谱、酶测定、组织学、图像 分析、激素重建实验以及使用受控环境室。我们 具体目标是：（1）确定介导性别相关差异的基因和蛋白质， 正常和/或自身免疫（即干燥综合征）患者泪腺和睑板腺的性类固醇控制 综合征）小鼠;（2）检查性和性类固醇对干眼发展的影响;和（3） 确定人类泪腺和睑板腺基因表达中存在的性别相关差异 腺体、角膜和结膜。这些研究的结果应该大大促进我们的理解 性和性类固醇影响眼前节的过程。此外，本发明还提供了一种方法， 这些发现可能与眼睛的健康有关，因为它们：（1）探索泪膜的调节; 和（2）可能导致开发用于临床治疗干眼综合征的特异性疗法。

The preocular tear film plays an essential role in maintaining ocular surface integrity, protecting against microbial challenge and preserving visual acuity. Tear film dysfunction, in turn, may severely impact the eye and lead to desiccation, ulceration and perforation of the cornea, an increased incidence of infectious disease, and pronounced visual impairment and blindness. Countless people suffer from tear film disorders, which are termed dry eye syndromes and are classified into 2 major types: aqueous-deficient and evaporative. Aqueous-deficient dry eye is due to decreased tear secretion from the lacrimal gland. An example is Sjogren's syndrome, a common autoimmune disease that afflicts primarily women and destroys the lacrimal gland. Evaporative dry eye is typically caused by meibomian gland dysfunction and may be a major cause of dry eye during menopause, use of estrogen replacement therapy and aging. The long range objectives of this grant application are to test our hypotheses that: (1) sex steroids are extremely important in the physiological regulation of the ocular surface and adnexa, as well as the production of the tear film; and (2) sex, sex steroid hormones, and in particular androgen deficiency, are critical etiologic factors in the pathogenesis of both aqueous-deficient and evaporative dry eye syndromes. Experimental procedures include mouse models, whole genome microarrays (e.g. gene chips), real-time-PCR, in situ hybridization, cell cultures, immunoassays, 2D gels, MALDI/mass spectrometry, enzyme assays, histology, image analysis, hormone reconstitution experiments, as well as use of a controlled environment chamber. Our specific aims are to: (1) identify the genes and proteins that mediate the sex-related differences in, and the sex steroid control of, lacrimal and meibomian glands in normal and/or autoimmune (i.e. Sjogren's syndrome) mice; (2) examine the influence of sex and sex steroids on the development of dry eye; and (3) identify the sex-related differences that exist in the gene expression of the human lacrimal and meibomian glands, cornea and conjunctiva. Results from these studies should significantly advance our understanding of the processes by which sex and sex steroids influence the anterior segment of the eye. In addition, findings may have health relatedness for the eye, because they: (1) explore the regulation of the tear film; and (2) may lead to the development of specific therapies for the clinical treatment of dry eye syndromes.