He Wei, Tang Panli, Lv Hongbin
Department of Ophthalmology, Taikang Sichuan Hospital, Chengdu, China.
Department of Cardiothoracic Surgery, The General Hospital of Western Theater Command, Chengdu, China.
Front Immunol. 2025 Jun 16;16:1571576. doi: 10.3389/fimmu.2025.1571576. eCollection 2025.
Diabetic retinopathy (DR) is a common and severe microvascular complication of diabetes, leading to vision impairment and blindness, particularly in working-age adults. Oxidative stress plays a central role in the pathogenesis of DR, with excessive reactive oxygen species (ROS) damaging retinal tissues, including blood vessels and neurons. This oxidative damage is exacerbated through various metabolic pathways, such as the polyol pathway, protein kinase C(PKC) activation, and advanced glycation end-product(AGE) formation. Additionally, mitochondrial dysfunction, retinal cell apoptosis, inflammation, and lipid peroxidation are key pathological processes associated with oxidative stress in DR. Epigenetic modifications, including DNA methylation and histone alterations, further contribute to gene expression changes induced by oxidative stress. To mitigate oxidative damage, therapeutic strategies targeting ROS production, neutralizing free radicals, and enhancing antioxidant defenses hold promise. Various natural antioxidant compounds, such as polyphenols (e.g., epigallocatechin-3-gallate, quercetin, resveratrol) and carotenoids (e.g., lutein, zeaxanthin), have demonstrated potential in reducing oxidative stress and improving retinal health in DR models. Moreover, activation of the Nrf2 and SIRT1 pathways has emerged as a promising approach to enhance the antioxidant response. Although preclinical studies show promising results, further clinical trials are necessary to validate the efficacy and safety of these therapeutic strategies. In conclusion, a better understanding of the molecular mechanisms underlying oxidative stress in DR and the development of multi-target therapies could provide more effective treatment options for DR patients.
糖尿病视网膜病变（DR）是糖尿病常见且严重的微血管并发症，可导致视力损害和失明，在工作年龄的成年人中尤为常见。氧化应激在DR的发病机制中起核心作用，过量的活性氧（ROS）会损害包括血管和神经元在内的视网膜组织。这种氧化损伤通过多种代谢途径加剧，如多元醇途径、蛋白激酶C（PKC）激活和晚期糖基化终产物（AGE）形成。此外，线粒体功能障碍、视网膜细胞凋亡、炎症和脂质过氧化是与DR氧化应激相关的关键病理过程。表观遗传修饰，包括DNA甲基化和组蛋白改变，进一步导致氧化应激诱导的基因表达变化。为减轻氧化损伤，针对ROS产生、中和自由基和增强抗氧化防御的治疗策略具有前景。各种天然抗氧化化合物，如多酚（如表没食子儿茶素-3-没食子酸酯、槲皮素、白藜芦醇）和类胡萝卜素（如叶黄素、玉米黄质），已在DR模型中显示出降低氧化应激和改善视网膜健康的潜力。此外，激活Nrf2和SIRT1途径已成为增强抗氧化反应的一种有前景的方法。尽管临床前研究显示出有希望的结果，但仍需要进一步的临床试验来验证这些治疗策略的有效性和安全性。总之，更好地理解DR氧化应激的分子机制以及开发多靶点疗法可为DR患者提供更有效的治疗选择。
