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探索表观遗传修饰作为青光眼潜在的生物标志物和治疗靶点

Exploring Epigenetic Modifications as Potential Biomarkers and Therapeutic Targets in Glaucoma.

作者信息

Tonti Emanuele, Dell'Omo Roberto, Filippelli Mariaelena, Spadea Leopoldo, Salati Carlo, Gagliano Caterina, Musa Mutali, Zeppieri Marco

机构信息

Eye Clinic, Policlinico Umberto I University Hospital, 00142 Rome, Italy.

Department of Medicine and Health Sciences "Vincenzo Tiberio", University of Molise, Via Francesco De Sanctis 1, 86100 Campobasso, Italy.

出版信息

Int J Mol Sci. 2024 Feb 29;25(5):2822. doi: 10.3390/ijms25052822.

Abstract

Glaucoma, a complex and multifactorial neurodegenerative disorder, is a leading cause of irreversible blindness worldwide. Despite significant advancements in our understanding of its pathogenesis and management, early diagnosis and effective treatment of glaucoma remain major clinical challenges. Epigenetic modifications, encompassing deoxyribonucleic acid (DNA) methylation, histone modifications, and non-coding RNAs, have emerged as critical regulators of gene expression and cellular processes. The aim of this comprehensive review focuses on the emerging field of epigenetics and its role in understanding the complex genetic and molecular mechanisms underlying glaucoma. The review will provide an overview of the pathophysiology of glaucoma, emphasizing the intricacies of intraocular pressure regulation, retinal ganglion cell dysfunction, and optic nerve damage. It explores how epigenetic modifications, such as DNA methylation and histone modifications, can influence gene expression, and how these mechanisms are implicated in glaucomatous neurodegeneration and contribute to glaucoma pathogenesis. The manuscript discusses evidence from both animal models and human studies, providing insights into the epigenetic alterations associated with glaucoma onset and progression. Additionally, it discusses the potential of using epigenetic modifications as diagnostic biomarkers and therapeutic targets for more personalized and targeted glaucoma treatment.

摘要

青光眼是一种复杂的多因素神经退行性疾病,是全球不可逆性失明的主要原因。尽管我们对其发病机制和治疗的理解有了显著进展,但青光眼的早期诊断和有效治疗仍然是重大的临床挑战。表观遗传修饰,包括脱氧核糖核酸(DNA)甲基化、组蛋白修饰和非编码RNA,已成为基因表达和细胞过程的关键调节因子。这篇综述的目的集中在表观遗传学这一新兴领域及其在理解青光眼复杂的遗传和分子机制中的作用。该综述将概述青光眼的病理生理学,强调眼压调节、视网膜神经节细胞功能障碍和视神经损伤的复杂性。它探讨了DNA甲基化和组蛋白修饰等表观遗传修饰如何影响基因表达,以及这些机制如何与青光眼性神经变性相关并促成青光眼的发病机制。该手稿讨论了来自动物模型和人体研究的证据,深入了解与青光眼发病和进展相关的表观遗传改变。此外,它还讨论了将表观遗传修饰用作诊断生物标志物和治疗靶点以实现更个性化和针对性的青光眼治疗的潜力。

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本文引用的文献

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Role of epigenetic regulation in glaucoma.表观遗传调控在青光眼发病机制中的作用。
Biomed Pharmacother. 2023 Dec;168:115633. doi: 10.1016/j.biopha.2023.115633. Epub 2023 Oct 6.
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Cell. 2023 Jan 19;186(2):305-326.e27. doi: 10.1016/j.cell.2022.12.027. Epub 2023 Jan 12.

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