Omics Laboratory, University of Iowa, Iowa City, Iowa, United States of America ; Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa, United States of America.
PLoS One. 2013 Nov 29;8(11):e82140. doi: 10.1371/journal.pone.0082140. eCollection 2013.
Human vitreoretinal diseases are due to presumed abnormal mechanical interactions between the vitreous and retina, and translational models are limited. This study determined whether nonstructural proteins and potential retinal biomarkers were expressed by the normal mouse vitreous and retina.
Vitreous and retina samples from mice were collected by evisceration and analyzed by liquid chromatography-tandem mass spectrometry. Identified proteins were further analyzed for differential expression and functional interactions using bioinformatic software.
We identified 1,680 unique proteins in the retina and 675 unique proteins in the vitreous. Unbiased clustering identified protein pathways that distinguish retina from vitreous including oxidative phosphorylation and neurofilament cytoskeletal remodeling, whereas the vitreous expressed oxidative stress and innate immunology pathways. Some intracellular protein pathways were found in both retina and vitreous, such as glycolysis and gluconeogenesis and neuronal signaling, suggesting proteins might be shuttled between the retina and vitreous. We also identified human disease biomarkers represented in the mouse vitreous and retina, including carbonic anhydrase-2 and 3, crystallins, macrophage inhibitory factor, glutathione peroxidase, peroxiredoxins, S100 precursors, and von Willebrand factor.
Our analysis suggests the vitreous expresses nonstructural proteins that functionally interact with the retina to manage oxidative stress, immune reactions, and intracellular proteins may be exchanged between the retina and vitreous. This novel proteomic dataset can be used for investigating human vitreoretinopathies in mouse models. Validation of vitreoretinal biomarkers for human ocular diseases will provide a critical tool for diagnostics and an avenue for therapeutics.
人类玻璃体视网膜疾病是由于玻璃体和视网膜之间假定的异常机械相互作用引起的，而转化模型有限。本研究旨在确定正常小鼠玻璃体和视网膜是否表达非结构蛋白和潜在的视网膜生物标志物。
通过眼球摘除术收集小鼠的玻璃体和视网膜样本，并通过液相色谱-串联质谱法进行分析。使用生物信息学软件进一步分析鉴定出的蛋白质的差异表达和功能相互作用。
我们在视网膜中鉴定出 1680 种独特的蛋白质，在玻璃体中鉴定出 675 种独特的蛋白质。无偏聚类鉴定出区分视网膜和玻璃体的蛋白途径，包括氧化磷酸化和神经丝细胞骨架重塑，而玻璃体则表达氧化应激和固有免疫途径。一些细胞内蛋白途径在视网膜和玻璃体中均有发现，如糖酵解和糖异生以及神经元信号转导，表明蛋白质可能在视网膜和玻璃体之间穿梭。我们还鉴定出了在小鼠玻璃体和视网膜中表达的人类疾病生物标志物，包括碳酸酐酶-2 和 3、晶体蛋白、巨噬细胞抑制因子、谷胱甘肽过氧化物酶、过氧化物酶、S100 前体和血管性血友病因子。
我们的分析表明，玻璃体表达的非结构蛋白与视网膜相互作用，以应对氧化应激、免疫反应，并且细胞内蛋白质可能在视网膜和玻璃体之间交换。这个新的蛋白质组数据集可用于在小鼠模型中研究人类玻璃体视网膜病变。验证用于人类眼部疾病的玻璃体视网膜生物标志物将为诊断提供关键工具，并为治疗开辟途径。
