Tear Film Lipid Compositional, Structural, Functional, Relationships, and Dry Eye

 描述（由申请人提供）：仅在美国，干眼症就影响超过600万人，并且可以被分类为与睑板腺功能障碍（MGD）相关的水产生缺陷（AD）和蒸发性。干眼的两种发展机制都具有泪膜（TF）不稳定的共同特征，具有快速的泪膜破裂时间，这表明可能存在导致不稳定的TF的共同结构异常。我们的光谱研究已经确定了几个潜在的异常TF脂质组成，可能有助于TF不稳定，包括萜类化合物，饱和，蛋白质和胆固醇酯。我们还发现了干眼症的碳氢化合物构象异常。例如，当睑脂中的萜类化合物水平如MGD中一样低时，TF不稳定并且患者具有干眼的体征和症状。当阿奇霉素治疗恢复萜类化合物时，TF稳定性恢复，患者不再有干眼症的体征和症状。通过研究具有广泛TF稳定性的样品，我们有最好的机会测试哪些部分对TF稳定性很重要。我们建议研究来自干眼患者（AD和MGD）的样本和来自亚洲人的样本，因为他们的干眼发病率比白人高80%。我们还将比较当干眼的体征和症状通过治疗得到改善时睑脂和TF脂质的组成变化。将研究TF脂质和睑脂，因为它们的组成略有不同（如果不是显著不同的话）。我们建议使用光谱，拉曼，红外光谱和核磁共振，以确定如何TF组合物与泪液膜的稳定性，在体外和体内相同的样品上测量。我们建议在体外测量的TF稳定性参数包括：表面压力-面积等温线，等环，表面流变学，表面拉曼和定量布鲁斯特角显微镜，以评估睑脂的横向弹性和能力的压缩和扩展在动态面积变化。我们建议在体内测量几个参数，包括泪液渗透压，破裂时间和眨眼率。TF脂质和睑脂的量和组成（特别是萜类化合物、饱和度、蛋白质和胆固醇酯的水平）、烃构象和脂质-蛋白质相互作用的自然和实验差异将使用主成分分析与TF稳定性相关，以确定睑脂中的哪些部分是否对TF稳定性重要，最终目标是开发增强TF稳定性的疗法。

 DESCRIPTION (provided by applicant): Dry eye affects over six million people in the United States alone and may be classified as aqueous production-deficient (AD) and evaporative, which is associated with meibomian gland dysfunction (MGD). Both mechanisms of development of dry eye share the common feature of instability of the tear film (TF) with rapid tear break-up time, suggesting there may be a shared structural abnormality of the TF that is responsible for the instability. Our spectroscopic studies have identified several potential abnormalities in the TF lipid composition that may contribute to TF instability including terpenoids, saturation, protein and cholesteryl esters. We also identified hydrocarbon conformational abnormalities with dry eye. For example, when terpenoid levels in meibum are low as in MGD, the TF is unstable and patients have the signs and symptoms of dry eye. When terpenoids are restored with azithromycin treatment, TF stability is restored and patients no longer have the signs and symptoms of dry eye. We have the best chance of testing which moieties are important to TF stability by studying samples with a wide range of TF stabilities. We propose to study samples from patients with dry eye (both AD and MGD) and samples from Asians because they have an 80% higher incidence of dry eye compared to Caucasians. We will also compare compositional changes in meibum and TF lipid when the signs and symptoms of dry eye are ameliorated with treatment. TF lipid and meibum will be studied since their composition is slightly if not significantly different. We propose to use spectroscopy, Raman, IR and NMR, to determine how TF composition relates to tear film stability measured in vitro and in vivo on the same sample. The TF stability parameters we propose to measure in vitro include: surface pressure-area isotherms, isocycles, surface rheology, surface Raman and quantitative Brewster angle microscopy to assess the meibum's lateral elasticity and capability of compressing and spreading during dynamic area changes. We propose to measure in vivo several parameters including tear osmolarity, break-up time and blink rate. Natural and experimental differences in TF lipid and meibum amount and composition (especially terpenoids, saturation, protein and levels of cholesteryl esters), hydrocarbon conformation, and lipid-protein interactions, will be correlated to TF stability using principle component analysis t determine if and which moieties in meibum are important to TF stability, with the ultimate goal of developing therapies to enhance TF stability.