Sex, sex steroids and dry eye syndromes

摘要 眼前泪膜在维持眼表完整性、防止 微生物挑战和保持视力。反过来，泪膜功能障碍可能会严重影响眼睛。 并导致角膜干燥、溃疡和穿孔，增加感染性疾病的发生率， 以及明显的视力障碍和失明。不计其数的人患有泪膜疾病，这是 干眼症被称为干眼症，分为两种主要类型：缺水和蒸发。含水- 干眼症是由于泪腺分泌泪液减少所致。Sj？gren综合征就是一个例子。 (SS)，一种常见的自身免疫性疾病，主要困扰女性并破坏泪腺。 蒸发性干眼通常是由汗腺功能障碍引起的，可能是干眼的主要原因。 在更年期，使用雌激素替代疗法和衰老。这笔赠款的长期目标 应用是为了验证我们的假设：(1)性类固醇在生理上极其重要 调节眼表和附件，以及泪膜的产生；和(2)性，性类固醇 荷尔蒙，尤其是雄激素缺乏，是这两种疾病发病的关键病因。 缺水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(如基因芯片)、实时聚合酶链式反应、细胞培养、免疫分析、二维凝胶、酶分析、 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 性激素和性激素影响正常和SS泪腺的机制；(2)解开 性行为和性激素对眉毛腺影响的过程；以及(3)探索性的作用 和性类固醇对眼表和/或表面活性蛋白的边界润滑和表面活性蛋白的控制 附件。这些研究的结果应该会极大地促进我们对 性别和性激素会影响眼球的前段。此外，研究结果可能有益于 与眼睛相关，因为它们：(1)探索泪膜的调节；以及(2)可能导致 干眼症临床治疗的特殊疗法的发展。

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.