Topographic differential analysis and function of age-related protein expression in the retinal pigment epithelium of Callithrix jacchus

蝼蛄视网膜色素上皮年龄相关蛋白表达的拓扑差异分析及功能

• 批准号: 278124156
• 负责人: Privatdozent Dr. Michael Böhm
• 金额: --
• 依托单位: Klinik für Erkrankungen des vorderen Augenabschnitts
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/278124156?language=en
• 关键词: Topographic; differential; analysis; function; age

Physiological aging hampers visual function in multifactorial ways. Age-related morphological alterations in the retina, the ascending visual pathway, and the visual cortex have to be considered alongside those in praeretinal structures, such as the cornea and lens. Comparative proteomic analyses of the retinas in macula-bearing marmosets and macula-less rats have identified proteins that are altered with maturation and aging. We discovered four age-regulated proteins that are common to both species: peroxiredoxin (Prx), Parkinson disease (autosomal recessive, early onset) 7 (DJ-1), stathmin (STMN), and beta-synuclein (SCNB). We also found an age-related regulation of those proteins within the ascending visual pathway of rats and monkeys. Those proteins have been not reported in the retina and/or in relation to aging before.The retinal pigment epithelium (RPE) is involved in complex functions associated with visual function and the protection of the retina in forming the retina-blood barrier. Physiological aging of the RPE results in morphological and functional alterations. Several ophthalmological diseases such as age-related macular degeneration (AMD) occur due to pathological changes of the RPE. We suggest that examining the role and function of the RPE in macula-bearing retinas will provide a better understanding of age-related disease, such as the AMD. Established laboratory animals such as mice and rats do not possess a macula, which hampers their use as models for AMD research.We will aim to determine the proteome and genome of the unaffected physiologically aged RPEs of common marmosets (Callithrix jacchus) at different age stages. Then, the localization of identified proteins as well as PRX, DJ1, SNCB, and STMN in the macular region and peripheral region will be scrutinized in prepared whole mounts of the RPE. The role and function of the selected proteins in the human-RPE cell line ARPE-19 will be investigated by analyzing specific and functional markers as well as major signaling pathways. The demographic development of an aging population makes it necessary to increase the amount of scientific research into the macular mechanisms involved in the aging process. A better understanding of aging could yield predictive factors to detect the conversion of physiological aging into pathological conditions.

生理老化以多因素的方式阻碍视觉功能。视网膜、上行视觉通路和视皮层中的视网膜相关形态学改变必须与视网膜前结构（例如角膜和透镜）中的那些形态学改变一起考虑。对有黄斑的绒猴和无黄斑的大鼠的视网膜进行比较蛋白质组学分析，发现了随着成熟和衰老而改变的蛋白质。我们发现了两个物种共有的四种年龄调节蛋白：过氧化物酶（Prx），帕金森病（常染色体隐性遗传，早发性）7（DJ-1），stathmin（STMN）和β-突触核蛋白（SCNB）。我们还发现，在大鼠和猴子的视觉上升通路中，这些蛋白质存在与年龄相关的调节作用。视网膜色素上皮（retinalpigmentepithelium，RPE）是视网膜的重要组成部分，它参与了与视功能相关的复杂功能，并在视网膜-血屏障的形成中起着保护视网膜的作用。RPE的生理老化导致形态和功能改变。几种眼科疾病如年龄相关性黄斑变性（AMD）由于RPE的病理变化而发生。我们认为，检查的作用和功能的视网膜色素上皮在黄斑轴承视网膜将提供一个更好地了解与年龄有关的疾病，如AMD。实验室动物如小鼠和大鼠没有黄斑，这阻碍了它们作为AMD研究模型的使用。我们的目标是确定普通绒猴（Callithrix jacchus）在不同年龄阶段的未受影响的生理老化RPE的蛋白质组和基因组。然后，将在制备的整个RPE标本中仔细检查所鉴定的蛋白质以及PRX、DJ 1、SNCB和STMN在黄斑区和外周区中的定位。将通过分析特异性和功能性标志物以及主要信号传导途径来研究所选蛋白在人RPE细胞系ARPE-19中的作用和功能。人口老龄化的人口发展使得有必要增加对衰老过程中涉及的黄斑机制的科学研究。更好地了解衰老可以产生预测因素，以检测生理衰老转化为病理状态。