Sex, sex steroids and dry eye syndromes

摘要 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，增加传染病的发病率， 严重的视力障碍和失明无数人患有泪膜疾病， 称为干眼综合征，并分为两种主要类型：缺水型和蒸发型。水- 干眼症是由于泪腺分泌的泪液减少所致。一个例子是干燥综合征 (SS)一种常见的自身免疫性疾病，主要折磨女性并破坏泪腺。 蒸发性干眼症通常由睑板腺功能障碍引起，可能是干眼症的主要原因 绝经期，使用雌激素替代疗法和衰老。这项补助金的长期目标 应用是为了验证我们的假设：（1）性类固醇是非常重要的生理 调节眼表和附件，以及泪膜的产生;和（2）性，性类固醇 激素，特别是雄激素缺乏，是两者发病机制中的关键致病因素。 水分缺乏和蒸发性干眼综合征。实验程序包括小鼠模型，整体 基因组微阵列（例如基因芯片），实时PCR，细胞培养，免疫测定，2D凝胶，酶测定， 组织学、图像分析和激素重建实验。我们的具体目标是：（1）确定 性和性类固醇影响正常和SS泪腺的机制;（2）解开 性激素对睑板腺作用的机制;（3）探讨性激素在睑板腺中的作用 和性类固醇控制眼表面的边界润滑和表面活性蛋白，和/或 附件这些研究的结果应该大大促进我们对这些过程的理解， 性和性类固醇影响眼前节。此外，研究结果可能具有健康 眼睛的相关性，因为他们：（1）探索泪膜的调节;（2）可能导致 开发用于临床治疗干眼综合征的特异性疗法。

ABSTRACT 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 Sj¿gren's syndrome (SS), 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, cell cultures, immunoassays, 2D gels, enzyme assays, histology, image analysis and hormone reconstitution experiments. Our specific aims are to: (1) determine the mechanisms by which sex and sex steroids influence the normal and SS lacrimal gland; (2) unravel the processes underling the sex and sex steroid effects on the meibomian gland; and (3) explore the role of sex and sex steroids in the control of boundary lubrication and surfactant proteins at the ocular surface and/or adnexa. 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.