Lyu Ying, Yin Qichuan, Liao Xiaodan, Xie Youxuan, Yang Hao, Cui Yilei, Han Yuqi, Yao Ke, Wang Chunru, Shentu Xingchao
Zhejiang University, Eye Center of Second Affiliated Hospital, School of Medicine, Zhejiang Provincial Key Laboratory of Ophthalmology, Zhejiang Provincial Clinical Research Center for Eye Diseases, Zhejiang Provincial Engineering Institute on Eye Diseases, Hangzhou, 310009, China.
Beijing National Laboratory for Molecular Sciences, Key Laboratory of Molecular Nanostructure and Nanotechnology, Nanostructure and Nanotechnology, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, China.
Biomaterials. 2025 Oct;321:123329. doi: 10.1016/j.biomaterials.2025.123329. Epub 2025 Apr 12.
Dry eye disease (DED) affects up to 50 % of the global population, leading to serious discomforts that affect patients' quality of life. In the multifactorial etiology of DED, oxidative stress is at the core, initiating a sequence of inflammatory responses and surface damage via a vicious cycle. However, current therapies merely have a narrow focus on inflammation. In this study, we developed a novel antioxidative eye drop, ethylenediamine (EDA)-modified C fullerene derivatives (abbreviated as FN-EDA), to break this vicious cycle. FN-EDA was successfully synthesized by modifying C fullerene with multiple ethylenediamine (EDA) groups, resulting in enhanced water solubility and a positive charge. This modification significantly improved ocular surface retention time, cellular uptake, and lysosomal escape in vitro. Therapeutically, FN-EDA significantly alleviated dry eye disease (DED) in a mouse model. It reduced corneal epithelial damage by 3.8-fold compared to 0.05 % cyclosporine A (CsA) and restored tear secretion to approximately 65 % of the normal level. Mechanistically, both in vivo and in vitro results demonstrate that FN-EDA is endowed with superior biological activity in effectively scavenging excessive oxidative stress, down-regulating proinflammatory cytokines expression, and promoting epithelial barrier reconstruction, even recovering corneal innervation. Thus, our findings open an avenue to make this multi-functional eye drop a promising candidate for DED.
干眼症（DED）影响着全球多达50%的人口，会导致严重不适，影响患者的生活质量。在干眼症的多因素病因中，氧化应激处于核心地位，它通过恶性循环引发一系列炎症反应和表面损伤。然而，目前的治疗方法仅仅局限于炎症方面。在本研究中，我们开发了一种新型抗氧化眼药水，乙二胺（EDA）修饰的C富勒烯衍生物（简称为FN-EDA），以打破这种恶性循环。通过用多个乙二胺（EDA）基团修饰C富勒烯成功合成了FN-EDA，从而提高了水溶性并使其带正电荷。这种修饰显著提高了其在眼表的保留时间、细胞摄取以及体外溶酶体逃逸能力。在治疗方面，FN-EDA在小鼠模型中显著减轻了干眼症（DED）。与0.05%的环孢素A（CsA）相比，它使角膜上皮损伤降低了3.8倍，并使泪液分泌恢复到正常水平的约65%。从机制上讲，体内和体外结果均表明，FN-EDA具有卓越的生物活性，能够有效清除过量的氧化应激、下调促炎细胞因子表达并促进上皮屏障重建，甚至恢复角膜神经支配。因此，我们的研究结果为使这种多功能眼药水成为治疗干眼症的有前景的候选药物开辟了一条途径。
