Muttuvelu Danson Vasanthan, Cehofski Lasse Jørgensen, Muhammad Misk Ghassan Farik, Chen Xiangjun, Utheim Tor Paaske, Khan Asif Manzoor, Abduljabar Ahmed Basim, Kristensen Kasper, Rasmussen Marie Louise Roed, Vorum Henrik, Heegaard Steffen, Honoré Bent
Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Department of Ophthalmology, Odense University Hospital, Odense, Denmark; Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
Ocul Surf. 2023 Jul;29:444-455. doi: 10.1016/j.jtos.2023.06.010. Epub 2023 Jun 20.
Anterior blepharitis is a frequent ocular condition which may result in severe ocular surface disease. In this study, advanced proteome analysis was performed to elucidate biological mechanisms underlying anterior blepharitis.
All patients underwent full ophthalmological examination including Ocular Surface Disease Index score (OSDI). Measurement of non-invasive break-up time (NBUT), Oxford score, and meibography were performed. Tear film samples from treatment naïve patients with anterior blepharitis (n = 15) and age-matched controls (n = 11) were collected with Schirmer filtration paper. The samples were analyzed with label-free quantification nano liquid chromatography - tandem mass spectrometry (LFQ nLC-MS/MS). Significantly regulated proteins were identified with a permutation-based calculation with a false discovery rate at 0.05.
Among the 927 proteins detected, a total of 162 proteins were significantly changed. Regulated proteins were involved in cytoplasmic translation, positive regulation of B cell activation, complement activation and phagocytosis. High levels of plakin proteins, a group of proteins involved in cytoskeleton organization, were observed in anterior blepharitis, including plectin, desmoplakin, envoplakin, epiplakin, periplakin, and vimentin. The upregulation of plectin was confirmed with single reaction monitoring. Patients with anterior blepharitis had lower levels of immunoglobulin chains, VEGF coregulated chemokine 1 (CXCL17), and platelet-derived growth factor C.
Anterior blepharitis was associated with a high level of plectin indicating a pronounced intracellular response with cytoskeletal reorganization. Our data suggest a lack of immunoglobulin chains and CXCL17 in anterior blepharitis with potential alterations in the ocular surface immune response.
睑缘炎是一种常见的眼部疾病,可能导致严重的眼表疾病。本研究进行了先进的蛋白质组分析,以阐明睑缘炎潜在的生物学机制。
所有患者均接受了全面的眼科检查,包括眼表疾病指数评分(OSDI)。进行了无创泪膜破裂时间(NBUT)、牛津评分和睑板腺造影测量。用Schirmer滤纸收集未经治疗的睑缘炎患者(n = 15)和年龄匹配的对照组(n = 11)的泪膜样本。样本采用无标记定量纳米液相色谱-串联质谱(LFQ nLC-MS/MS)进行分析。通过基于排列的计算,以0.05的错误发现率鉴定出显著调节的蛋白质。
在检测到的927种蛋白质中,共有162种蛋白质发生了显著变化。调节的蛋白质参与细胞质翻译、B细胞活化的正向调节、补体活化和吞噬作用。在睑缘炎患者中观察到高水平的斑块蛋白,这是一组参与细胞骨架组织的蛋白质,包括网蛋白、桥粒斑蛋白、内褶蛋白、表皮斑蛋白、周斑蛋白和波形蛋白。通过单反应监测证实了网蛋白的上调。睑缘炎患者的免疫球蛋白链、VEGF共调节趋化因子1(CXCL17)和血小板衍生生长因子C水平较低。
睑缘炎与高水平的网蛋白有关,表明细胞内有明显反应并伴有细胞骨架重组。我们的数据表明睑缘炎患者缺乏免疫球蛋白链和CXCL17,眼表免疫反应可能发生改变。