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

生理性衰老对视觉功能的影响是多方面的。视网膜、上升视觉通路和视觉皮层中与年龄相关的形态学改变必须与视网膜前结构（如角膜和晶状体）中的形态学改变一并考虑。对有黄斑的狨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。我们发现了这两个物种共有的四种年龄调节蛋白：过氧化物还氧蛋白（Prx）、帕金森病（常染色体隐性，早发）7 （j -1）、stathmin （STMN）和β -突触核蛋白（SCNB）。我们还发现，在老鼠和猴子的上升视觉通路中，这些蛋白质与年龄有关。这些蛋白质以前没有在视网膜和/或与衰老有关的报道。视网膜色素上皮（RPE）参与与视觉功能和视网膜保护相关的复杂功能，形成视网膜-血液屏障。RPE的生理性老化导致形态和功能的改变。一些眼科疾病，如年龄相关性黄斑变性（AMD）是由于RPE的病理改变而发生的。我们建议，检查RPE在黄斑视网膜中的作用和功能，将有助于更好地了解与年龄相关的疾病，如AMD。已建立的实验动物，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。我们的目的是确定在不同年龄阶段的普通狨猴（Callithrix jacchus）未受生理衰老影响的rpe的蛋白质组和基因组。然后，鉴定的蛋白以及PRX、DJ1、SNCB和STMN在黄斑区域和外周区域的定位将在制备的RPE整片中仔细检查。选择的蛋白在人rpe细胞系ARPE-19中的作用和功能将通过分析特异性和功能标记以及主要信号通路来研究。随着人口老龄化的发展，有必要增加对黄斑老化机制的科学研究。更好地了解衰老可以产生预测因素，以检测生理衰老向病理状态的转化。

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.