The role of (O-acyl)-omega-hydroxy fatty acids in human lipid layer structure and function in health and meibomian gland dysfunction.

(O-酰基)-omega-羟基脂肪酸在人体脂质层结构和健康及睑板腺功能障碍中的作用。

• 批准号: 9157220
• 负责人: JASON Jay NICHOLS
• 金额: $ 36.75万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9157220
• 关键词: Affect; American; Appearance; Biochemical; Classification; Communicable Diseases; Custom; Desiccation; Disease; Electrospray Ionization; Eye diseases; Film; Foundations; Functional disorder; Goals; Health; Homeostasis; Human; Image; Individual; Inflammation; Island; Lead; Lipids; Literature; Mass Spectrum Analysis; Measures; Methodology; Methods; Microscope; Molecular; Molecular Weight; Optics; Osmolalities; Patients; Pharmacologic Substance; Population; Positioning Attribute; Public Health; Quality of life; Reporting; Research; Resolution; Risk; Role; Rupture; Stress; Structure; Structure-Activity Relationship; Symptoms; System; Testing; Thick; Time; United States Food and Drug Administration; Work; aqueous; base; clinical practice; clinically significant; evaporation; eye dryness; hydroxy fatty acid; imaging system; improved; in vivo; innovation; insight; knowledge translation; lens; meibomian gland; meibomian gland dysfunction; microscopic imaging; molecular marker; novel; ocular surface; optical imaging; pressure; tandem mass spectrometry; targeted treatment

Project Summary Meibomian gland dysfunction (MGD) is one of the most prevalent ophthalmic conditions with millions of Americans suffering from the condition. In addition to burdensome symptoms, meibum and tear film alterations from MGD can impact ocular health by leading to ocular surface desiccation and an increased risk of inflammation or infectious disease and an abnormal ocular flora. Although these things are becoming better understood, the molecular basis for the mechanisms of lipid layer and tear film disruption are not well understood. Initial evidence from the literature and preliminary studies suggests that the O-acyl omega hydroxy fatty acids (OAHFAs) found in the meibum and tear film lipids are associated with increased in vivo lipid layer disruption and tear film thinning. The long-term goal of this research is to identify a molecular marker that predicts structural and functional changes in the meibum and tear film such that it may be considered a potential targeted therapeutic. Specific Aim #1 is targeted to quantitate and identify OAHFAs that are proposed to be decreased in the meibum and tear film in MGD. Quantitative differences will be determined using mass spectrometry, with class and species identification resultant from electrospray ionization (ESI) with a quadrupole time-of-flight (q-TOF) tandem MS for high resolution mass and structural information and SWATH analysis. Specific Aim #2 is targeted to determine the structural impact of the decrease in OAHFAs on the lipid layer of the tear film (e.g., reduced thickness, non-uniform lipid lens appearance); a high resolution microscope will be used to study the in vivo structure of the lipid layer. Specific Aim #3 will determine the functional impact of the disorganization of the lipid layer relative to increased evaporation of the aqueous tear film via rapid tear film thinning. In Specific Aim #3, a non-invasive interferometric optical system will be used to measure tear film thinning on the ocular surface in relation to Specific Aims #1 and #2.

项目概要 睑板腺功能障碍 (MGD) 是最常见的眼科疾病之一 数百万美国人患有这种疾病。除了繁重的症状外，睑脂 MGD 导致的泪膜改变会导致眼表损伤，从而影响眼部健康 干燥、炎症或传染病以及眼部异常的风险增加 植物区系。尽管人们对这些事情的了解越来越多，但其分子基础 脂质层和泪膜破坏的机制尚不清楚。初步证据来自 文献和初步研究表明，O-酰基欧米茄羟基脂肪酸 睑脂和泪膜脂质中发现的 (OAHFAs) 与体内脂质层增加有关 破坏和泪膜变薄。这项研究的长期目标是确定一种分子 预测睑脂和泪膜结构和功能变化的标记物，以便 可能被认为是一种潜在的靶向治疗。 具体目标 #1 旨在量化和识别建议的 OHFFA MGD 中睑脂和泪膜减少。数量差异将通过以下方式确定 质谱法，通过电喷雾电离进行类别和物种鉴定 (ESI) 与四极杆飞行时间 (q-TOF) 串联 MS 用于高分辨率质量和结构 信息和 SWATH 分析。具体目标 #2 旨在确定结构性影响 泪膜脂质层上的 OHFFA 减少（例如，厚度减少、不均匀） 脂质晶状体外观）；高分辨率显微镜将用于研究体内结构 脂质层。具体目标#3将决定组织解散的功能影响 脂质层相对于通过快速泪膜变薄而增加的水性泪膜蒸发。在 具体目标#3，将使用非侵入式干涉光学系统来测量泪膜 与具体目标 #1 和 #2 相关的眼表变薄。