Sex, sex steroids and dry eye syndromes

性、性类固醇和干眼症

• 批准号: 8033022
• 负责人: David A. Sullivan
• 金额: $ 63.91万
• 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 2014-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8033022
• 关键词: Aging; American; Androgen Antagonists; Androgen-Insensitivity Syndrome; Androgens; Anterior eyeball segment structure; Applications Grants; Autoimmune Diseases; Binding; Biological Assay; Blindness; Blinking; Caring; Cell Culture Techniques; Chronic; Clinical Treatment; Communicable Diseases; Cornea; Desiccation; Development; Disease; Dry Eye Syndromes; Enzymes; Epithelial Cells; Estrogen Replacement Therapy; Estrogens; Etiology; Eye; Eyelid structure; Film; Functional disorder; Gel; Gender Role; Gene Chips; Gene Expression Regulation; Gene Proteins; Genome; Gonadal Steroid Hormones; Health; Histology; Hormonal; Hormones; Image Analysis; Immunoassay; Incidence; Inflammation; Knowledge; Lacrimal gland structure; Lead; Lesion; Lipids; Lubrication; Mediating; Menopausal Symptom; Menopause; Pathogenesis; Patients; Perforation; Pharmaceutical Preparations; Physiological; Play; Postmenopause; Prevalence; Procedures; Process; Production; Proteins; Public Health; Quality of life; Regulation; Research; Risk; Role; Signs and Symptoms; Sjogren' s Syndrome; Syndrome; Testing; Therapeutic; Time; Tissues; Translating; Ulcer; Vision; Visit; Visual Acuity; Visual impairment; Woman; aqueous; base; conjunctiva; effective therapy; evaporation; eye dryness; improved functioning; insight; lacrimal; meibomian gland; meibomian gland dysfunction; microbial; mouse model; ocular surface; prevent; protein expression; receptor; reconstitution; research study; sex; surfactant

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: Dry eye syndrome is one of the leading causes of patient visits to eye care practitioners, as well as an important public health problem that has no cure. This disease afflicts over 30 million Americans, predominantly women, and significantly impacts their quality of life. We propose to determine why dry eye occurs primarily in women and to translate our research results into the development of new and unique therapeutic strategies to treat aqueous-deficient and evaporative dry eye.

描述（由申请人提供）：眼前泪膜在维持眼表完整性、防止微生物攻击和保持视力方面起着重要作用。泪膜功能障碍反过来可能严重影响眼睛，导致角膜干燥、溃疡和穿孔，增加感染性疾病的发病率，以及明显的视力损害和失明。无数的人患有泪膜疾病，这被称为干眼综合征，并分为2个主要类型：水分缺乏和蒸发。水缺乏性干眼症是由于泪腺分泌的泪液减少.一个例子是干燥综合征（SS），一种常见的自身免疫性疾病，主要困扰妇女和破坏泪腺。蒸发性干眼通常由睑板腺功能障碍引起，并且可能是绝经期、使用雌激素替代疗法和衰老期间干眼的主要原因。本基金申请的长期目标是检验我们的假设：（1）性类固醇在眼表和附件的生理调节以及泪膜的产生中极其重要;和（2）性、性类固醇激素，特别是雄激素缺乏，是缺水性和蒸发性干眼综合征发病机制中的关键病因因素。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、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）确定性激素和性类固醇影响正常泪腺和SS泪腺的机制;（2）阐明性激素和性类固醇对睑板腺影响的过程;（3）探索性激素和性类固醇在控制眼表和/或附件的边界润滑和表面活性蛋白中的作用。这些研究的结果将大大促进我们对性和性类固醇影响眼前节的过程的理解。此外，这些发现可能与眼睛健康相关，因为它们：（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定疗法。 公共卫生相关性：干眼综合征是患者就诊于眼科护理从业者的主要原因之一，也是一个无法治愈的重要公共卫生问题。这种疾病折磨着超过3000万美国人，主要是女性，并严重影响他们的生活质量。我们建议确定干眼主要发生在女性中的原因，并将我们的研究结果转化为治疗缺水性和蒸发性干眼的新的独特的治疗策略。