Glyoxalase System as a Therapeutic Target against Diabetic Retinopathy.
Glyoxalase System as a Therapeutic Target against Diabetic Retinopathy.
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DOI：
10.3390/antiox9111062
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发表时间：
2020-10-30
期刊：
影响因子：
--
通讯作者：
Bejarano E
中科院分区：
文献类型：
--
作者：
Aragonès G;Rowan S;G Francisco S;Yang W;Weinberg J;Taylor A;Bejarano E
高血糖是糖尿病的一个定义特征，与氧化应激相结合，会导致晚期糖基化终产物（AGEs）的形成。AGEs是有毒化合物，对包括视网膜和透镜在内的许多组织具有不利影响。AGEs促进活性氧（ROS）的形成，反过来又促进AGEs的产生，导致正反馈循环，这是一种损害组织适应性的恶性循环。氧化应激和AGEs的积累与包括糖尿病视网膜病变（DR）在内的多种疾病的发病机制有关。DR是糖尿病的一种破坏性微血管并发症，也是工作年龄成人失明的主要原因。DR的发生和发展是多因素的。降低AGEs的积累可能是一种潜在的治疗方法，以减缓这种威胁视力的糖尿病并发症。设置DR在生理背景下，在这篇评论中，我们首先描述氧化应激，形成AGEs，和老化的眼睛，其中每一个都与一个主要的年龄相关的眼部病理组织之间的关系。本文综述了AGEs的产生机制和抗AGEs解毒系统。我们特别强调了视网膜中的谷胱甘肽酶系统在预防与DR相关的AGEs相关损伤中的潜力。我们提供了野生型小鼠不同组织中谷胱甘肽酶活性的比较分析，支持谷胱甘肽酶系统在视网膜中AGEs解毒中的重要作用，并提出了该系统的操作作为预防DR发作的治疗策略。
Hyperglycemia, a defining characteristic of diabetes, combined with oxidative stress, results in the formation of advanced glycation end products (AGEs). AGEs are toxic compounds that have adverse effects on many tissues including the retina and lens. AGEs promote the formation of reactive oxygen species (ROS), which, in turn, boost the production of AGEs, resulting in positive feedback loops, a vicious cycle that compromises tissue fitness. Oxidative stress and the accumulation of AGEs are etiologically associated with the pathogenesis of multiple diseases including diabetic retinopathy (DR). DR is a devastating microvascular complication of diabetes mellitus and the leading cause of blindness in working-age adults. The onset and development of DR is multifactorial. Lowering AGEs accumulation may represent a potential therapeutic approach to slow this sight-threatening diabetic complication. To set DR in a physiological context, in this review we first describe relations between oxidative stress, formation of AGEs, and aging in several tissues of the eye, each of which is associated with a major age-related eye pathology. We summarize mechanisms of AGEs generation and anti-AGEs detoxifying systems. We specifically feature the potential of the glyoxalase system in the retina in the prevention of AGEs-associated damage linked to DR. We provide a comparative analysis of glyoxalase activity in different tissues from wild-type mice, supporting a major role for the glyoxalase system in the detoxification of AGEs in the retina, and present the manipulation of this system as a therapeutic strategy to prevent the onset of DR.
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