Sheng Siting, Zhao Huiling, Liu Lirui, Chen Dan, Wu Xingdi, Liu Chujun, Ma Xinyu, Xu Jing-Wei, Ji Jian, Han Haijie, Xu Wen
Eye Center, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Provincial Key Laboratory of Ophthalmology, Zhejiang Provincial Clinical Research Center for Eye Diseases, Zhejiang Provincial Engineering Institute on Eye Diseases, Hangzhou, 310009, China.
Eye Center, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang Provincial Key Laboratory of Ophthalmology, Zhejiang Provincial Clinical Research Center for Eye Diseases, Zhejiang Provincial Engineering Institute on Eye Diseases, Hangzhou, 310009, China; Department of Ophthalmology, The Fourth Affiliated Hospital Zhejiang University School of Medicine, Yiwu, China.
Biomaterials. 2025 Nov;322:123353. doi: 10.1016/j.biomaterials.2025.123353. Epub 2025 Apr 20.
Uveitis, a frequently recurrent inflammatory condition of the uvea, poses a significant risk of visual impairment and blindness, primarily due to the excessive generation of reactive oxygen species (ROS) and the activation of signaling pathways that propagate inflammatory responses. Despite the widespread use of corticosteroid eye drops as a standard treatment, these therapies are hindered by limited efficacy, adverse side effects, and poor ocular bioavailability. To address these challenges, polyethyleneimine (PEI)-modified polydopamine (PDA) carrying microRNA-132-3p (miR-132), namely PEI/PDA@miR-132, was developed to simultaneously neutralize ROS and attenuate inflammation in experimental models of acute and chronic uveitis. Mechanistically, PEI/PDA@miR-132 demonstrated remarkable efficacy by suppressing ROS production, inhibiting the pro-inflammatory polarization of macrophages, and downregulating the IκBα/nuclear factor-kappa B (NF-κB) p65 signaling pathway. These effects culminated in the reduction of pro-inflammatory cytokines and mitigation of apoptosis. Therapeutically, PEI/PDA@miR-132 provided significant relief from hallmark symptoms of uveitis, including iris congestion, inflammatory exudation, and retinal folds, while exhibiting superior retinal safety compared to commercially available dexamethasone. Furthermore, it showcased excellent biocompatibility, positioning it as a promising therapeutic strategy for managing oxidative stress- and inflammation-driven diseases such as acute and chronic uveitis.
葡萄膜炎是一种葡萄膜频繁复发的炎症性疾病，主要由于活性氧（ROS）的过度产生以及传播炎症反应的信号通路的激活，导致视力损害和失明的重大风险。尽管皮质类固醇眼药水作为标准治疗方法被广泛使用，但这些疗法受到疗效有限、副作用大以及眼部生物利用度差的阻碍。为了应对这些挑战，开发了携带微小RNA - 132 - 3p（miR - 132）的聚乙烯亚胺（PEI）修饰的聚多巴胺（PDA），即PEI/PDA@miR - 132，以在急性和慢性葡萄膜炎的实验模型中同时中和ROS并减轻炎症。从机制上讲，PEI/PDA@miR - 132通过抑制ROS产生、抑制巨噬细胞的促炎极化以及下调IκBα/核因子 - κB（NF - κB）p65信号通路，显示出显著的疗效。这些作用最终导致促炎细胞因子的减少和细胞凋亡的减轻。在治疗方面，PEI/PDA@miR - 132显著缓解了葡萄膜炎的标志性症状，包括虹膜充血、炎症渗出和视网膜褶皱，同时与市售地塞米松相比，表现出更高的视网膜安全性。此外，它还展示了出色的生物相容性，使其成为治疗氧化应激和炎症驱动疾病（如急性和慢性葡萄膜炎）的有前景的治疗策略。
