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

项目摘要 睑板腺功能障碍（MGD）是最普遍的眼科病症之一， 数百万美国人患有这种疾病。除了沉重的症状外， MGD引起的泪膜改变可通过导致眼表 干燥和炎症或传染病的风险增加，以及眼部异常 植物群。虽然这些事情正在变得更好地理解， 脂质层和泪膜破坏的机制还不清楚。初步证据来自 文献和初步研究表明O-酰基ω-羟基脂肪酸 在睑脂和泪膜脂质中发现的OAHFA与体内脂质层的增加有关。 破裂和泪膜变薄。这项研究的长期目标是确定一种分子 一种预测睑脂和泪膜结构和功能变化的标记物， 可以被认为是一种潜在的靶向治疗剂。 具体目标#1旨在定量和鉴别拟定用于 MGD组睑脂和泪膜减少。定量差异将使用 质谱法，通过电喷雾电离进行类别和种类鉴定 (ESI)使用四极杆飞行时间（q-TOF）串联MS进行高分辨率质量和结构 信息和SWATH分析。具体目标#2旨在确定结构影响 泪膜脂质层上OAHFA的减少（例如，厚度减小，不均匀 脂质透镜外观）;高分辨率显微镜将用于研究 脂质层。具体目标#3将决定组织结构混乱的功能影响。 脂质层相对于通过快速泪膜变薄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 与特定目标#1和#2相关的眼表变薄。

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.