Aminated fullerene for comprehensive dry eye therapy: Promoting epithelial-barrier reconstruction and nerve regeneration by suppressing oxidation and inflammation

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 C₇₀ fullerene derivatives (abbreviated as FN-EDA), to break this vicious cycle. FN-EDA was successfully synthesized by modifying C₇₀ 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.