Keratoconjunctivitis Sicca and Conjunctival Antigen-Presenting Cells

干燥性角结膜炎和结膜抗原呈递细胞

• 批准号: 432369380
• 负责人: Dr. Aytan Musayeva
• 金额: --
• 依托单位: Schepens Eye Research Institute
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 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/432369380?language=en
• 关键词: Keratoconjunctivitis; Sicca; Conjunctival; Antigen; Presenting

Keratoconjunctivitis sicca (KCS), also known as dry eye syndrome, is a chronic, progressive, inflammatory ocular disease characterized by chronic dryness and inflammation of the corneal and conjunctival surfaces. KCS is one of the most prevalent eye diseases. The pathogenesis includes activation of stress pathways on the ocular surface by desiccation resulting in production of inflammatory cytokines by epithelial cells, intraepithelial lymphocytes and infiltrating CD4+ T cells. It has recently been reported that the number of mature antigen presenting cells (APCs) correlated with disease severity and conjunctival goblet cell loss in patients with KCS related to Sjogren’s syndrome. However, it remains to be established, whether this also applies to more common forms of KCS.The goal of the research project is to test the hypothesis that the number of mature APCs in the conjunctiva correlates with disease severity in patients with KCS. The primary objective is to compare the number of mature APCs in impression cytology samples from patients with KCS and controls and to correlate the findings with markers of clinical severity. Secondary objectives are (1) to compare the numbers of individual subgroups of APCs (dendritic cells, macrophages, monocytes) and correlate these with clinical findings and (2) to compare tear MUC5AC (Mucin 5AC, a major secreted mucin of goblet cells) concentration and the number of goblet cells in impression cytology samples from patients with KCS and controls and to correlate the findings with disease markers.Patients with moderate to severe KCS and healthy control subjects will be examined with regard to symptoms using established questionnaires. Quantity and quality of tear film will be determined by Schirmer’s test, tear meniscus height measurement and fluorescein tear break-up time. MUC5AC concentration in tear protein extracted from Schirmer test strips will be measured by ELISA. Quality of the ocular surface will be assessed by fluorescein and lissamine green staining. Moreover, conjunctival cells will be harvested by impression cytology to measure conjunctival goblet cell density and to evaluate chemokine receptor expression in immune cells with flow cytometry.The findings of the study will enhance our understanding of the pathophysiology of KCS by determining if maturation of certain APC populations is associated with goblet cell loss and clinical severity. Discovering biomarkers with greater disease specificity will represent a major advance in diagnostic classification. Moreover, the findings of the study may become helpful to monitor disease progression and to verify the efficacy or the possible toxicity of the therapeutic regimen.

干燥性角膜结膜炎（KCS），也称为干眼综合征，是一种慢性、进行性、炎性眼部疾病，其特征在于角膜和结膜表面的慢性干燥和炎症。KCS是最常见的眼部疾病之一。发病机制包括通过干燥激活眼表面上的应激途径，导致上皮细胞、上皮内淋巴细胞和浸润性CD4+ T细胞产生炎性细胞因子。最近有报道，成熟抗原呈递细胞（APC）的数量与疾病的严重程度和结膜杯状细胞的损失与干燥综合征相关的KCS患者。然而，这是否也适用于更常见的KCS形式仍有待确定。该研究项目的目标是检验结膜中成熟APC的数量与KCS患者疾病严重程度相关的假设。主要目的是比较KCS患者和对照组印迹细胞学样本中成熟APC的数量，并将结果与临床严重程度的标志物相关联。次要目的是（1）比较APC个体亚组的数量（2）比较泪液MUC5AC（树突状细胞、巨噬细胞、单核细胞），并将其与临床发现相关联，（粘蛋白5AC，杯状细胞的主要分泌粘蛋白）本发明的目的在于比较来自KCS患者和对照的印迹细胞学样品中杯状细胞的浓度和数量，并将发现与疾病标志物相关联。使用已建立的问卷调查表检查中度至重度KCS和健康对照受试者的症状。泪膜的数量和质量将通过泪液分泌试验、泪液半月板高度测量和荧光素泪膜破裂时间来确定。将通过ELISA测量从Schirmer测试条提取的泪液蛋白中的MUC5AC浓度。将通过荧光素和丽丝胺绿色染色评估眼表质量。此外，结膜细胞将收获印迹细胞学测量结膜杯状细胞密度和评估免疫细胞中的趋化因子受体表达与流式cytometer.The研究结果将提高我们的理解KCS的病理生理学，确定是否某些APC人口的成熟与杯状细胞的损失和临床严重程度。发现具有更高疾病特异性的生物标志物将代表诊断分类的重大进展。此外，该研究的结果可能有助于监测疾病进展并验证治疗方案的疗效或可能的毒性。