Sex, sex steroids and dry eye syndromes

性、性类固醇和干眼症

• 批准号: 7534769
• 负责人: David A. Sullivan
• 金额: $ 67.57万
• 依托单位: SCHEPENS EYE RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-30 至 2010-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7534769
• 关键词: Age; Androgen Antagonists; Androgens; Anterior eyeball segment structure; Applications Grants; Autoimmune Diseases; Autoimmune Process; Binding; Biological Assay; Blindness; Cell Culture Techniques; Chronic; Clinical; Clinical Treatment; Communicable Diseases; Cornea; Desiccation; Development; Disease; Dry Eye Syndromes; Enzymes; Epithelial Cells; Estrogen Replacement Therapy; Estrogens; Etiology; Eye; Film; Functional disorder; Gel; Gene Chips; Gene Expression; Gene Expression Regulation; Gene Proteins; Genome; Gonadal Steroid Hormones; Health; Histology; Hormones; Human; Image Analysis; Immunoassay; In Situ Hybridization; Incidence; Inflammation; Knowledge; Lacrimal gland structure; Lead; Lesion; Lipids; Mass Spectrum Analysis; Mediating; Menopausal Symptom; Menopause; Mus; Pathogenesis; Perforation; Pharmaceutical Preparations; Physiological; Play; Postmenopause; Predisposition; Prevalence; Procedures; Process; Production; Regulation; Research; Risk; Role; Signs and Symptoms; Sjogren' s Syndrome; Testing; Therapeutic; Time; Tissues; Translating; Ulcer; Variant; Vision; Visual Acuity; Visual impairment; Woman; aqueous; base; conjunctiva; controlled environment chamber; evaporation; eye dryness; improved functioning; insight; lacrimal; meibomian gland; meibomian gland dysfunction; microbial; mouse model; ocular surface; prevent; receptor; reconstitution; research study; sex

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.

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 疾病，以及明显的视力障碍和失明。无数人遭受泪膜紊乱之苦， 它们被称为干眼综合征，主要分为两种类型：缺水和缺水 挥发的。缺水干眼是由于泪腺分泌泪液减少所致。一个 例如Sjogren综合征，这是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眉板腺功能障碍引起的，可能是 绝经期干眼的主要原因，雌激素替代疗法的使用和衰老。长距离的 这项拨款申请的目的是检验我们的假设：(1)性类固醇在 眼表和附件的生理调节，以及泪膜的产生； (2)性、性类固醇激素，尤其是雄激素缺乏，是导致 水分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)、实时定量聚合酶链式反应、原位杂交 细胞培养、免疫分析、2D凝胶、MALDI/MS、酶分析、组织学、图像 分析，荷尔蒙重建实验，以及使用受控环境舱。我们的 具体的目标是：(1)识别与性别有关的差异的基因和蛋白质，以及 性类固醇激素对正常和/或自身免疫(即干燥综合征)患者泪腺和眉板腺的控制 综合症)小鼠；(2)检验性和性类固醇对干眼发育的影响；以及(3) 确定人类泪腺和眉毛基因表达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会极大地促进我们对 性激素和性激素影响眼前节的过程。此外, 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； 以及(2)可能导致临床治疗干眼症的特定疗法的发展。