Keratoconjunctivitis Sicca: The importance of protein glycosylation for tear filmstability

干燥性角结膜炎：蛋白质糖基化对泪膜稳定性的重要性

• 批准号: 406073788
• 负责人: Professor Dr. Franz H. Grus
• 金额: --
• 依托单位: Augenklinik und Poliklinik
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2022-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/406073788?language=en
• 关键词: Keratoconjunctivitis; Sicca; importance; protein; glycosylation

Dry Eye Disease, also known as Keratoconjunctivitis Sicca (KCS), is defined as a multifactorial disease of the tear film and ocular surface. Its symptoms include visual disturbance, tear film instability accompanied by morphological changes and inflammation of the ocular surface. Suspected causes range from tear film deficiency and changes in tear film composition to an involvement of the immune system. The involvement of various factors from the tear film shows the heterogenic character of the disease. Thus, changes in the lipid layer, as well as differential protein compositions might be causative. Appropriate therapies are urgently needed but yet missing. Glycosylation patterns of tear film proteins are altered in Dry Eye patients. These influence protein structure and stability and accordingly the protein binding properties. Furthermore, they play an important role in molecular processes, e.g. protein-lipid interactions. The primary goal of our project is to improve understanding of the relevance of protein-glycosylation for tear film stability and for Dry Eye pathogenesis. We will investigate quantitative and qualitative glycoproteomic differences between Dry Eye patients and healthy subjects. To that end we will investigate which proteins show altered glycosylation patterns, what role these proteins play for the function of the tear film and how glycosylation influences the integrity of the tear film. Moreover, we want to use potential protein glycosylation patterns to distinguish between different Dry Eye subtypes and degrees of severety. Furthermore, we will investigate how glycosylation patterns of tear film proteins influence lipid interactions. Our project aims at analysing glycosylation patterns and their influence on the integrity of the tear film. This will help to better understand Dry Eye pathogenesis and improve diagnostics and in the long run even therapy of Dry Eye.

干眼症，也称为干燥性角膜结膜炎（KCS），被定义为泪膜和眼表的多因素疾病。其症状包括视力障碍、泪膜不稳定伴眼表形态改变和炎症。怀疑的原因范围从泪膜缺陷和泪膜成分的变化到免疫系统的参与。泪膜中多种因素的参与显示了该病的异质性。因此，脂质层的变化，以及差异蛋白质组成可能是病因。我们迫切需要适当的治疗方法，但目前还没有。干眼患者泪膜蛋白的糖基化模式改变。这些影响蛋白质的结构和稳定性，从而影响蛋白质的结合特性。此外，它们在分子过程中发挥重要作用，例如蛋白质-脂质相互作用。我们项目的主要目标是提高对蛋白糖基化与泪膜稳定性和干眼发病机制相关性的理解。我们将研究干眼症患者和健康受试者之间的定量和定性糖蛋白质组学差异。为此，我们将研究哪些蛋白质显示出改变的糖基化模式，这些蛋白质对泪膜的功能起什么作用，以及糖基化如何影响泪膜的完整性。此外，我们希望使用潜在的蛋白质糖基化模式来区分不同的干眼症亚型和严重程度。此外，我们将研究糖基化模式的泪膜蛋白影响脂质相互作用。我们的项目旨在分析糖基化模式及其对泪膜完整性的影响。这将有助于更好地了解干眼症的发病机制，改善诊断，并从长远来看，甚至治疗干眼症。