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[摘要]
糖尿病视网膜病变(DR)是糖尿病(DM)最常见的微血管并发症,其病理机制涉及微血管病变、慢性炎症、氧化应激及代谢记忆效应等多个层面。然而,当前临床诊疗仍面临早期诊断困难和治疗效果有限的挑战。近年来,以N6-甲基腺苷(m6A)为代表的RNA甲基化修饰作为表观转录组调控的核心机制,在DR的病理生理过程中展现出重要作用。m6A修饰由甲基转移酶(如METTL3)、去甲基酶(如FTO、ALKBH5)及结合蛋白(如YTHDF家族)协同调控,通过影响RNA代谢参与多种病理过程。同时,m6A与非编码RNA(miRNA、lncRNA、circRNA)之间形成复杂的协同调控网络,在DR的关键病理环节中发挥重要作用。文章系统梳理现有研究,旨在构建以RNA甲基化为核心的DR调控网络图谱,不仅深化对DR发病机制的理解,也为开发基于m6A的新型诊断标志物与靶向治疗策略提供理论依据。
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[Abstract]
Diabetic retinopathy(DR)is the most prevalent microvascular complication associated with diabetes mellitus(DM). Its pathological mechanisms encompass various factors, including microvascular lesions, chronic inflammation, oxidative stress, and metabolic memory effects. Nevertheless, current clinical practices in the diagnosis and treatment encounter significant challenges, particularly regarding early detection and the limited efficacy of therapeutic interventions. Recently, RNA methylation modifications, particularly N6-methyladenosine(m6A), have emerged as a central mechanism in the epigenetic regulation of the transcriptome, playing a crucial role in the pathophysiological processes underlying DR. The regulation of m6A modification is a synergistic process involving methyltransferases(such as METTL3), demethylases(such as FTO and ALKBH5), and binding proteins(such as the YTHDF family), which collectively influence RNA metabolism and participate in various pathological processes. Additionally, m6A interacts within a complex cooperative regulatory network alongside non-coding RNAs(including miRNA, lncRNA, and circRNA), significantly contributing to the key pathological mechanisms of DR. This article systematically reviews the existing literature, with the objective of constructing a regulatory network map for DR centered on RNA methylation. This review not only enhances the understanding of the pathogenesis of DR but also provides a theoretical foundation for developing novel diagnostic markers and targeted treatment strategies based on m6A.
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