The Role of Lipoxidation in the Pathogenesis of Diabetic Retinopathy.
The Role of Lipoxidation in the Pathogenesis of Diabetic Retinopathy.
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脂氧化在糖尿病视网膜病变发病机制中的作用
DOI：
10.3389/fendo.2020.621938
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发表时间：
2020
影响因子：
5.2
通讯作者：
Curtis TM
中科院分区：
文献类型：
--
作者：
Augustine J;Troendle EP;Barabas P;McAleese CA;Friedel T;Stitt AW;Curtis TM
由于与活性氧（ROS）的相互作用，脂质可以发生修饰。例如，脂质过氧化导致产生多种高反应性醛类物质，其可以驱动细胞和组织中的一系列疾病相关反应。此类脂质醛与包括磷脂、核酸和蛋白质的大分子上的亲核基团反应，这进而导致形成称为高级脂氧化终产物（ALE）的可逆或不可逆加合物。在糖尿病背景下，脂质过氧化和ALE形成与大血管和微血管并发症的发病机制有关。视网膜病变作为糖尿病最常见的并发症，是全球范围内视力丧失和失明的主要原因之一。在此，我们讨论糖尿病视网膜病变（DR）作为一种疾病的实体，并审查目前的知识和实验数据支持的作用，脂质过氧化和ALE的形成，这种情况的发生和发展。潜在的治疗方法，以防止脂质过氧化和脂质氧化反应在糖尿病视网膜也被认为是，包括使用抗氧化剂，脂质醛清除剂和药理学和基因治疗方法，以促进内源性醛解毒系统。结论是，在这一领域的进一步研究可能会导致新的策略，以阻止DR的进展之前，不可逆的视网膜损伤和视力威胁的并发症发生。
Lipids can undergo modification as a result of interaction with reactive oxygen species (ROS). For example, lipid peroxidation results in the production of a wide variety of highly reactive aldehyde species which can drive a range of disease-relevant responses in cells and tissues. Such lipid aldehydes react with nucleophilic groups on macromolecules including phospholipids, nucleic acids, and proteins which, in turn, leads to the formation of reversible or irreversible adducts known as advanced lipoxidation end products (ALEs). In the setting of diabetes, lipid peroxidation and ALE formation has been implicated in the pathogenesis of macro- and microvascular complications. As the most common diabetic complication, retinopathy is one of the leading causes of vision loss and blindness worldwide. Herein, we discuss diabetic retinopathy (DR) as a disease entity and review the current knowledge and experimental data supporting a role for lipid peroxidation and ALE formation in the onset and development of this condition. Potential therapeutic approaches to prevent lipid peroxidation and lipoxidation reactions in the diabetic retina are also considered, including the use of antioxidants, lipid aldehyde scavenging agents and pharmacological and gene therapy approaches for boosting endogenous aldehyde detoxification systems. It is concluded that further research in this area could lead to new strategies to halt the progression of DR before irreversible retinal damage and sight-threatening complications occur.