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The endoplasmic reticulum: Homeostasis and crosstalk in retinal health and disease
Progress in Retinal and Eye Research ( IF 18.6 ) Pub Date : 2023-12-12 , DOI: 10.1016/j.preteyeres.2023.101231
Sarah X Zhang 1 , Josh J Wang 2 , Christopher R Starr 3 , Eun-Jin Lee 4 , Karen Sophia Park 2 , Assylbek Zhylkibayev 3 , Andy Medina 2 , Jonathan H Lin 4 , Marina Gorbatyuk 3
Affiliation  

The endoplasmic reticulum (ER) is the largest intracellular organelle carrying out a broad range of important cellular functions including protein biosynthesis, folding, and trafficking, lipid and sterol biosynthesis, carbohydrate metabolism, and calcium storage and gated release. In addition, the ER makes close contact with multiple intracellular organelles such as mitochondria and the plasma membrane to actively regulate the biogenesis, remodeling, and function of these organelles. Therefore, maintaining a homeostatic and functional ER is critical for the survival and function of cells. This vital process is implemented through well-orchestrated signaling pathways of the unfolded protein response (UPR). The UPR is activated when misfolded or unfolded proteins accumulate in the ER, a condition known as ER stress, and functions to restore ER homeostasis thus promoting cell survival. However, prolonged activation or dysregulation of the UPR can lead to cell death and other detrimental events such as inflammation and oxidative stress; these processes are implicated in the pathogenesis of many human diseases including retinal disorders. In this review manuscript, we discuss the unique features of the ER and ER stress signaling in the retina and retinal neurons and describe recent advances in the research to uncover the role of ER stress signaling in neurodegenerative retinal diseases including age-related macular degeneration, inherited retinal degeneration, achromatopsia and cone diseases, and diabetic retinopathy. In some chapters, we highlight the complex interactions between the ER and other intracellular organelles focusing on mitochondria and illustrate how ER stress signaling regulates common cellular stress pathways such as autophagy. We also touch upon the integrated stress response in retinal degeneration and diabetic retinopathy. Finally, we provide an update on the current development of pharmacological agents targeting the UPR response and discuss some unresolved questions and knowledge gaps to be addressed by future research.



中文翻译:


内质网:视网膜健康和疾病中的稳态和串扰



内质网(ER)是最大的细胞内细胞器,执行广泛的重要细胞功能,包括蛋白质生物合成、折叠和运输、脂质和甾醇生物合成、碳水化合物代谢以及钙储存和门控释放。此外,内质网与线粒体、质膜等多种细胞内细胞器密切接触,主动调节这些细胞器的生物发生、重塑和功能。因此,维持内质网稳态和功能性对于细胞的生存和功能至关重要。这一重要过程是通过精心策划的未折叠蛋白反应 (UPR) 信号通路来实现的。当错误折叠或未折叠的蛋白质在内质网中积累时,UPR 被激活(这种情况称为内质网应激),并发挥恢复内质网稳态的作用,从而促进细胞存活。然而,UPR 的长期激活或失调可能导致细胞死亡和其他有害事件,例如炎症和氧化应激;这些过程与包括视网膜疾病在内的许多人类疾病的发病机制有关。在这篇综述手稿中,我们讨论了视网膜和视网膜神经元中 ER 和 ER 应激信号传导的独特特征,并描述了揭示 ER 应激信号传导在神经退行性视网膜疾病(包括年龄相关性黄斑变性、遗传性黄斑变性)中的作用的最新研究进展。视网膜变性、全色盲和视锥细胞疾病以及糖尿病性视网膜病变。在某些章节中,我们重点介绍了内质网与其他细胞内细胞器(重点关注线粒体)之间复杂的相互作用,并说明了内质网应激信号如何调节常见的细胞应激途径(例如自噬)。 我们还探讨了视网膜变性和糖尿病视网膜病变中的综合应激反应。最后,我们提供了针对 UPR 反应的药物当前开发的最新信息,并讨论了一些未解决的问题和未来研究需要解决的知识差距。

更新日期:2023-12-17
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