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原发性开角型青光眼和假性剥脱性青光眼患者泪液中的差异蛋白表达

Differential protein expression in tears of patients with primary open angle and pseudoexfoliative glaucoma.

作者信息

Pieragostino Damiana, Bucci Sonia, Agnifili Luca, Fasanella Vincenzo, D'Aguanno Simona, Mastropasqua Alessandra, Ciancaglini Marco, Mastropasqua Leonardo, Di Ilio Carmine, Sacchetta Paolo, Urbani Andrea, Del Boccio Piero

机构信息

Department of Biomedical Sciences, University G. d'Annunzio of Chieti-Pescara, Via dei Vestini, 66100 Chieti, Italy.

出版信息

Mol Biosyst. 2012 Apr;8(4):1017-28. doi: 10.1039/c1mb05357d. Epub 2011 Nov 29.

Abstract

Primary open angle (POAG) and pseudoexfoliative glaucoma (PXG) are the most common primary and secondary forms of glaucoma, respectively. Even though the patho-physiology, aqueous humor composition, risk factors, clinical features, therapy and drug induced ocular surface changes in POAG and PXG have been widely studied, to date information concerning tear protein characterization is lacking. Tears are a source of nourishment for ocular surface tissues and a vehicle to remove local waste products, metabolized drugs and inflammatory mediators produced in several ophthalmic diseases. In glaucoma, the proteomic definition of tears may provide insights concerning patho-physiology of the disease and ocular surface modifications induced by topical therapy. Our study aimed at characterizing protein patterns in tears of patients with medically controlled POAG and PXG. A comparative tears proteomic analysis by label-free LC-MS(E) highlighted differences in the expression of several proteins in the two glaucoma sub-types and control subjects, highlighting inflammation pathways expressed in both diseases. Results were independently reconfirmed by SDS-PAGE and linear MALDI-TOF MS, validating altered levels of Lysozyme C, Lipocalin-1, Protein S100, Immunoglobulins and Prolactin Inducible Protein. Moreover, we found a differential pattern of phosphorylated Cystatin-S that distinguishes the two pathologies. The most relevant results suggest that in both pathologies there may be active inflammation pathways related to the disease and/or induced by therapy. We show, for the first time, tear protein patterns expressed under controlled intraocular pressure conditions in POAG and PXG subjects. These findings could help in the understanding of molecular machinery underlying these ophthalmologic diseases, resulting in early diagnosis and more specific therapy.

摘要

原发性开角型青光眼(POAG)和剥脱性青光眼(PXG)分别是最常见的原发性和继发性青光眼类型。尽管POAG和PXG的病理生理学、房水成分、危险因素、临床特征、治疗以及药物引起的眼表变化已得到广泛研究,但迄今为止,有关泪液蛋白质特征的信息仍然缺乏。泪液是眼表组织的营养来源,也是清除局部废物、代谢药物和几种眼科疾病中产生的炎症介质的载体。在青光眼中,泪液的蛋白质组学定义可能有助于深入了解疾病的病理生理学以及局部治疗引起的眼表改变。我们的研究旨在对药物控制的POAG和PXG患者的泪液蛋白质模式进行特征分析。通过无标记液相色谱-质谱联用(LC-MS(E))进行的泪液蛋白质组比较分析突出了两种青光眼亚型与对照受试者中几种蛋白质表达的差异,突显了两种疾病中表达的炎症途径。通过十二烷基硫酸钠-聚丙烯酰胺凝胶电泳(SDS-PAGE)和线性基质辅助激光解吸电离飞行时间质谱(linear MALDI-TOF MS)独立地再次证实了结果,验证了溶菌酶C、脂质运载蛋白-1、蛋白质S100、免疫球蛋白和催乳素诱导蛋白水平的改变。此外,我们发现磷酸化胱抑素-S的差异模式可区分这两种病理状态。最相关的结果表明,在这两种病理状态下,可能存在与疾病相关和/或由治疗诱导的活跃炎症途径。我们首次展示了POAG和PXG受试者在眼压控制条件下表达的泪液蛋白质模式。这些发现有助于理解这些眼科疾病的分子机制,从而实现早期诊断和更具针对性的治疗。

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