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 眉板腺功能障碍(MGD)是最常见的眼科疾病之一， 数以百万计的美国人患有这种疾病。除了令人不快的症状外，meiban MGD引起的泪膜改变会导致眼表损害，从而影响眼睛健康。 干燥，炎症或感染性疾病的风险增加，以及眼睛异常 弗洛拉。尽管这些事情正在变得更好地被理解，但 脂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 (OAHFAs)与体内脂肪层的增加有关 破裂和泪膜变薄。这项研究的长期目标是识别一种分子 一种标记物，可预测膜和泪膜的结构和功能变化，从而使其 可能被认为是一种潜在的靶向治疗。 具体目标#1的目标是量化和识别建议的 MGD患者泪膜和泪膜减少。数量差异将使用以下方法确定 电喷雾电离产生的具有类别和物种鉴定的质谱学 (ESI)和四极飞行时间(Q-TOF)串联质谱仪用于高分辨率质量和结构 信息和条带分析。具体目标2旨在确定结构性影响 泪膜脂层上OAHFAs的减少(例如，厚度减少，不均匀 脂肪晶体的外观)；高分辨率显微镜将被用来研究体内结构 脂层。具体目标#3将确定解体的功能影响 脂层是由于泪膜迅速变薄而使含水泪膜蒸发增加所致。在……里面 具体目标#3，一种非侵入式干涉光学系统将被用来测量泪膜 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.