Macula-less rat and macula-bearing monkey retinas exhibit common lifelong proteomic changes
Macula-less rat and macula-bearing monkey retinas exhibit common lifelong proteomic changes
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DOI：
10.1016/j.neurobiolaging.2013.04.020
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发表时间：
2013-11-01
影响因子：
4.2
通讯作者：
Thanos, Solon
中科院分区：
文献类型：
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作者：
Boehm, Michael R. R.;Mertsch, Sonja;Thanos, Solon
与年龄相关的神经视网膜改变的视觉后果已得到充分记录，但对其分子基础知之甚少。我们对狨猴和大鼠的视网膜进行了比较蛋白质组分析，以确定表达谱随着成熟和衰老而改变的蛋白质。使用二维凝胶电泳比较新生儿、青少年、中年和老年视网膜的蛋白质谱。基质辅助解吸电离飞行时间质谱法揭示了大鼠和狨猴中常见的蛋白质，这些蛋白质在整个生命周期中表现出浓度变化。对所选蛋白质及其 mRNA 进行蛋白质印迹、定量逆转录酶聚合酶链反应和免疫组织化学分析，以确定蛋白质组学鉴定的变化是否可以在细胞和分子水平上得到验证。我们发现了这两个物种共有的 4 种蛋白质（帕金森病 [常染色体隐性遗传，早发] 7/DJ-1、stathmin、过氧化还原蛋白和 β-突触核蛋白），其浓度随着年龄的增长而调节。这些发现得到了蛋白质印迹、免疫组织化学和定量逆转录聚合酶链反应分析的证实。这些蛋白质位于两个物种视网膜内的某些细胞层和细胞亚群中。这些蛋白质在成人视网膜中的表达通过免疫组织化学得到证实。本研究首次提供证据证明视网膜的生理学特征是其蛋白质组的特定终生变化。这些变化与视网膜是否具有黄斑无关，发生在视觉信号处理过程中的关键功能通路中，并且可能参与与年龄相关的病理实体的发展。 (C) 2013 Elsevier Inc. 保留所有权利。
The visual consequences of age-related alterations in the neural retina have been well documented, but little is known about their molecular bases. We performed a comparative proteomic analysis of the retinas in marmosets and rats to identify proteins for which the expression profiles are altered with maturation and aging. Protein profiles were compared in the newborn, juvenile, middle-age, and aged retinas using 2-dimensional gel electrophoresis. Matrix-assisted desorption ionizationetime-of-flight mass spectrometry revealed common proteins in rats and marmosets that exhibited changes in concentration throughout life. Western blot, quantitative reverse-transcriptase polymerase chain reaction, and immunohistochemistry analyses of selected proteins and their mRNA were used to determine whether the changes identified by proteomics were verifiable at the cellular and molecular levels. We found 4 proteins common to both species (Parkinson disease [autosomal recessive, early onset] 7/DJ-1, stathmin, peroxiredoxin, and beta-synuclein) whose concentrations were regulated with age. These findings were confirmed by Western blot, immunohistochemistry, and quantitative reverse-transcriptase polymerase chain reaction analyses. The proteins were localized in certain layers and subsets of cells within the retinas of both species. The expression of these proteins in the adult human retina was confirmed with immunohistochemistry. The present study is the first to provide evidence that the retina is physiologically characterized by specific lifelong changes in its proteome. These changes are independent of whether the retina bears a macula, occur in key functional pathways during the processing of visual signals, and might be involved in the development of age-related pathologic entities. (C) 2013 Elsevier Inc. All rights reserved.