Biochemistry and Biophysics of the Preocular Tear Film

眼前泪膜的生物化学和生物物理学

• 批准号: 8230756
• 负责人: Igor A Butovich
• 金额: $ 30.45万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8230756
• 关键词: 3-Dimensional; Accounting; Address; Affect; Anti-Bacterial Agents; Attention; Biochemical; Biochemistry; Biophysics; Cell membrane; Chronic; Climate; Complex; Development; Diagnostic tests; Differential Scanning Calorimetry; Disease; Drops; Drug Prescriptions; Dry Eye Syndromes; Elderly woman; Environmental Risk Factor; Evaluation; Eye; FDA approved; Film; Fluorescence Microscopy; Free Energy; Gel; General Population; Goals; Human; Hydrophobic Interactions; Indium; Lead; Life; Link; Lipids; Lipoproteins; Liquid substance; Modeling; Nanostructures; Nature; Nutritional; Osmolalities; Patients; Periodicity; Pharmaceutical Preparations; Phase; Placebos; Property; Proteins; Proteomics; Publications; Quality of life; Reporting; Research; Risk; Role; Sampling; Seasons; Sodium Chloride; Source; Structure; Structure-Activity Relationship; Surface; Symptoms; Techniques; Technology; Temperature; Testing; Therapeutic Effect; Time; Ulcer; Variant; Vision; aqueous; biophysical chemistry; effective therapy; eye dryness; liquid crystal; meibomian gland; meibomian gland dysfunction; ocular surface; public health relevance; research study; sample collection; self assembly; three dimensional structure; tool; two-dimensional; viscoelasticity

DESCRIPTION (provided by applicant): Dry eye (DE), and one of its major forms - chronic posterior blepharitis (CPB) - is a widespread multifactorial disease that diminishes the quality of life of millions of people, especially elderly, women, and those who live in adverse climates, by impairing their vision. Up to 30% of the general population is affected by DE. No effective treatment for DE exists at present with the only FDA-approved drug for treating DE and CPB, Restasis(R), having a therapeutic effect in 15% of patients vs. 5% in the placebo group. The disease is linked to changes in the very thin lipid- and protein rich ocular surface structure called tear film (TF). The long-term goals of our project are: 1) to redefine the biochemical composition and 3-D structure of TF, and 2) to determine the major biochemical and biophysical factors that stabilize or destabilize TF and hence those components important for the development of CPB and DE in general. Our general hypotheses are that: 1) the lipid composition of TF is more elaborate than previously thought; 2) the TF structure is stabilized due to very specific lipid/lipid and lipid/protein interactions; and, 3) TF is not quite liquid but instead has either a liquid crystal-like, or a gel-like structure and is composed of gradually intercalating layers and zones enriched with particular types of molecules and supramolecular complexes. The aims of the project are as follows. Aim 1. To challenge the current views on the biochemical composition of human TF as formed primarily of MGS by comparatively characterizing the lipids of MGS and AT, determining the lipid components of TF and their likely sources, and identifying and evaluating the roles of the critical lipid components in the formation and maintaining of TF. Aim 2. To test the hypothesis that normal TF is not quite liquid but instead has an either liquid crystal-like or a gel- like dynamic nanostructure composed of gradually intercalating layers and zones enriched with particular types of molecules and supramolecular complexes which is stabilized by ionic and hydrophilic/hydrophobic interactions between lipids, proteins, and other molecules and whose structure is susceptible to changes due to alterations in its lipid and protein compositions, tear osmolality, ocular temperature, mixing, environmental factors, etc. Aim 3. To determine whether or not there are cyclic qualitative and quantitative changes in human AT lipids and MGS that could be associated with the cyclic increase of DE symptoms and TF instability in CPB patients compared with normal subjects. PUBLIC HEALTH RELEVANCE: Dry eye syndrome (DE) in general, and one of its major forms - chronic posterior blepharitis (CPB) - is a wide- spread condition that severely deteriorates the quality of life of millions of people by impairing their vision. No effective treatment for DE exists at present with the only FDA approved prescription drug for treating CPB, Restasis(R), having a therapeutic effect in 15% of patients vs. 5% in the placebo group. The disease is related to abnormal changes in lipids and proteins in the preocular tear film (TF). The goal of the project is to investigate the biochemical changes in lipid composition of human aqueous tears and meibomian gland secretions and the corresponding biophysical changes in TF that occur in CPB in order to uncover their mechanisms and develop more effective diagnostic tests and treatments of this condition.

描述（由申请人提供）：干眼症（DE）及其主要形式之一 - 慢性后睑缘炎（CPB） - 是一种广泛的多因素疾病，可降低数百万人，尤其是老年人，妇女和那些人的生活质量生活在不利的气候下，通过损害他们的视野。多达30％的普通人群受DE的影响。目前尚无对DE的有效治疗方法，它使用FDA批准的药物治疗DE和CPB，Restasis（R），在15％的患者中具有治疗作用，而安慰剂组为5％。该疾病与称为泪膜（TF）的非常薄的脂质和蛋白质眼表面结构的变化有关。我们项目的长期目标是：1）重新定义TF的生化组成和3-D结构，以及2）确定稳定或破坏TF的主要生化和生物物理因素，因此对于这些组件的发展，因此对于开发的成分很重要CPB和DE一般。我们的一般假设是：1）TF的脂质组成比以前想象的要精致； 2）由于非常特异的脂质/脂质和脂质/蛋白质相互作用，TF结构被稳定下； 3）TF不是很液体，而是具有液晶状的，或类似凝胶的结构，由逐渐插入层和区域组成，并富含特定类型的分子和超分子复合物。该项目的目的如下。目的1。挑战当前对人类TF生化组成的观点，主要是通过相对表征MGS和AT的MG形成的，确定TF的脂质成分及其可能的来源，并确定和评估和评估和评估和评估和评估和评估和评估和评估和评估TF的形成和维持中的脂质成分。目的2。为了测试正常TF不是很液体的假设，而是具有液晶状的或类似凝胶的动态纳米结构，该纳米结构由逐渐插入的层和富含特定类型的分子和超分子复合物的区域组成，该区域由该纳米结构稳定在脂质，蛋白质和其他分子之间的离子和亲水性/疏水性相互作用，其结构易于由于其脂质和蛋白质成分的改变而易变的变化，泪液渗透压，眼部温度，混合，环境因素，环境因素等。与正常受试者相比，在脂质和MGS中，人类和MGS中人类症状的循环增加和TF不稳定性的循环质量增加和TF不稳定性可能相关的人类的循环定性和定量变化。 公共卫生相关性：一般而言，干眼症综合症（DE）及其主要形式之一 - 慢性后睑缘炎（CPB） - 是一种广泛的传播状况，可通过损害其视力来严重恶化数百万人的生活质量。目前尚无对DE的有效治疗方法，只有FDA批准的处方药用于治疗CPB，Restasis（R），在15％的患者中具有治疗作用，而安慰剂组为5％。该疾病与眼部催泪膜（TF）中脂质和蛋白质的异常变化有关。该项目的目的是调查人类水性眼泪和梅博米亚腺分泌物脂质组成的生化变化，以及CPB中TF中相应的生物物理变化，以发现其机制并开发更有效的诊断测试和治疗这种情况。 。