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首页> 外文期刊>Investigative ophthalmology & visual science >Tear fluid proteome reveals inflammation and immune response proteins as potential predictive biomarkers of the effects of desiccating stress and dry eye treatments
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Tear fluid proteome reveals inflammation and immune response proteins as potential predictive biomarkers of the effects of desiccating stress and dry eye treatments

机译：泪液蛋白质组揭示了炎症和免疫反应蛋白，是干燥压力和干眼症治疗效果的潜在预测生物标志物

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Purpose : To determine if tear protein biomarkers would predict the effects of topical steroid treatment and desiccating stress (DS) in dry eye (DE) patients. Methods : In a randomized double-masked controlled clinical trial (Pinto-Fraga, Ophthalmology 2015), patients (n=28) were treated topically with either 0.1% fluorometholone (FML) or polyvinyl alcohol (PA). Tear samples were collected at baseline (V1) and after 21-day treatment period (before (V2) and after (V3) a 2-hour exposure to DS in a controlled environment laboratory) with 1??l capillary tubes. Proteins were analyzed for library generation and relative quantification of expression levels in 2.6 ??g of tear proteins was carried out by NanoLC-MSTripleTOF using SWATH acquisition. Ocular surface integrity (corneal and conjunctival staining) was selected as the key DE-related sign along with proteomic data. Statistical analysis was performed with R software. Results : A protein identification library consisting of 870 proteins (FDR 1 %) was established. In total 770 proteins were identified and relatively quantified. Protein baseline values and treatment, FML or PA, were used to predict the DE-related sign changes between initial and visits before and after a 2-hour controlled adverse environment exposure. We identified 32 potentially predictive proteins for conjunctival staining change (V1-V2, treatment effect) and 73 for V2-V3-change (DS effect). Two tear proteins, lysozyme C LYZ (V1-V2: R2=0.44, V2-V3: R2=0.56) and prolactin-inducible protein PIP (V1-V2: R2=0.441, V2-V3: R2=0.506), were found in common between the two results (both proteins had p-value0.001 for the regression models). When the baseline protein expression value was higher, conjunctival staining of FML-treated patients was predicted to decrease more than in equivalent PA-treated patients. We also identified 22 potentially predictive proteins for corneal staining change between baseline and V2 and 14 of these proteins were immunoglobulins connected to complement activation. Conclusions : Using only a 1??l sample, we reliably identified 770 proteins from each analysed sample for DE patients. Potential biomarkers were identified for predicting treatment effects with desiccating stress in DE patients. This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
机译：目的：确定眼泪蛋白生物标记物是否可以预测局部类固醇治疗和干眼症（DE）患者的脱水压力（DS）的效果。方法：在一项随机的双掩蔽对照临床试验（Pinto-Fraga，眼科2015）中，患者（n = 28）分别接受0.1％氟甲酮（FML）或聚乙烯醇（PA）的局部治疗。在基线（V1）和21天治疗期后（在V2之前和（V3）在受控环境实验室中将DS暴露2小时之后）用1升的毛细管收集泪液样品。分析蛋白质的文库生成，并使用SWATH采集，通过NanoLC-MSTripleTOF对2.6微克泪液蛋白质中的表达水平进行相对定量。眼表完整性（角膜和结膜染色）与蛋白质组学数据一起被选为与DE相关的关键体征。用R软件进行统计分析。结果：建立了包含> 870种蛋白质（FDR 1％）的蛋白质鉴定文库。总共鉴定并相对定量了770种蛋白质。蛋白质基线值和治疗（FML或PA）用于预测2小时受控不良环境暴露前后初次和就诊之间的DE相关体征变化。我们确定了32种可能预测蛋白的结膜染色变化（V1-V2，治疗效果）和73种V2-V3变化（DS效果）。发现了两个泪液蛋白，溶菌酶C LYZ（V1-V2：R2 = 0.44，V2-V3：R2 = 0.56）和催乳素诱导蛋白PIP（V1-V2：R2 = 0.441，V2-V3：R2 = 0.506）。这两个结果之间有共同点（对于回归模型，两种蛋白质的p值均<0.001）。当基线蛋白表达值较高时，FML治疗患者的结膜染色预计比同等PA治疗的患者减少更多。我们还确定了22种在基线和V2之间角膜染色变化的潜在预测蛋白，其中14种蛋白是与补体激活相关的免疫球蛋白。结论：仅使用1？l样品，我们就从每个分析的样品中为DE患者可靠地鉴定了770种蛋白质。确定了潜在的生物标志物，以预测DE患者脱水压力的治疗效果。这是提交给2016年5月1-5日在华盛顿州西雅图市举行的2016 ARVO年会的摘要。

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