Kaštelan Snježana, Konjevoda Suzana, Sarić Ana, Urlić Iris, Lovrić Ivana, Čanović Samir, Matejić Tomislav, Šešelja Perišin Ana
Department of Ophthalmology, Clinical Hospital Dubrava, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia.
Department of Ophthalmology, Zadar General Hospital, 23000 Zadar, Croatia.
Molecules. 2025 Aug 4;30(15):3262. doi: 10.3390/molecules30153262.
Diabetic retinopathy (DR) is a progressive, multifactorial complication of diabetes and one of the major global causes of visual impairment. Its pathogenesis involves chronic hyperglycaemia-induced oxidative stress, inflammation, mitochondrial dysfunction, neurodegeneration, and pathological angiogenesis, as well as emerging systemic contributors such as gut microbiota dysregulation. While current treatments, including anti-vascular endothelial growth factor (anti-VEGF) agents, corticosteroids, and laser photocoagulation, have shown clinical efficacy, they are largely limited to advanced stages of DR, require repeated invasive procedures, and do not adequately address early neurovascular and metabolic abnormalities. Resveratrol (RSV), a naturally occurring polyphenol, has emerged as a promising candidate due to its potent antioxidant, anti-inflammatory, neuroprotective, and anti-angiogenic properties. This review provides a comprehensive analysis of the molecular mechanisms by which RSV exerts protective effects in DR, including modulation of oxidative stress pathways, suppression of inflammatory cytokines, enhancement of mitochondrial function, promotion of autophagy, and inhibition of pathological neovascularisation. Despite its promising pharmacological profile, the clinical application of RSV is limited by poor aqueous solubility, rapid systemic metabolism, and low ocular bioavailability. Various routes of administration, including intravitreal injection, topical instillation, and oral and sublingual delivery, have been investigated to enhance its therapeutic potential. Recent advances in drug delivery systems, including nanoformulations, liposomal carriers, and sustained-release intravitreal implants, offer potential strategies to address these challenges. This review also explores RSV's role in combination therapies, its potential as a disease-modifying agent in early-stage DR, and the relevance of personalised medicine approaches guided by metabolic and genetic factors. Overall, the review highlights the therapeutic potential and the key translational challenges in positioning RSV as a multi-targeted treatment strategy for DR.
糖尿病视网膜病变（DR）是糖尿病的一种进行性、多因素并发症，也是全球视力损害的主要原因之一。其发病机制涉及慢性高血糖诱导的氧化应激、炎症、线粒体功能障碍、神经退行性变和病理性血管生成，以及诸如肠道微生物群失调等新出现的全身因素。虽然目前的治疗方法，包括抗血管内皮生长因子（anti-VEGF）药物、皮质类固醇和激光光凝，已显示出临床疗效，但它们在很大程度上仅限于DR的晚期阶段，需要重复进行侵入性操作，并且不能充分解决早期神经血管和代谢异常问题。白藜芦醇（RSV）是一种天然存在的多酚，由于其强大的抗氧化、抗炎、神经保护和抗血管生成特性，已成为一种有前途的候选药物。本综述全面分析了RSV在DR中发挥保护作用的分子机制，包括氧化应激途径的调节、炎性细胞因子的抑制、线粒体功能的增强、自噬的促进以及病理性新生血管形成的抑制。尽管RSV具有良好的药理学特性，但其临床应用受到水溶性差、全身代谢快和眼部生物利用度低的限制。为了提高其治疗潜力，人们已经研究了包括玻璃体内注射、局部滴注以及口服和舌下给药在内的各种给药途径。药物递送系统的最新进展，包括纳米制剂、脂质体载体和缓释玻璃体内植入物，提供了应对这些挑战的潜在策略。本综述还探讨了RSV在联合治疗中的作用、其作为早期DR疾病修饰剂的潜力以及以代谢和遗传因素为指导的个性化医疗方法的相关性。总体而言，本综述强调了将RSV定位为DR多靶点治疗策略的治疗潜力和关键转化挑战。
