Abstract
Background
Cataract remains the most prevalent cause of visual impairment and irreversible blindness worldwide. It is characterized by lens opacification arising from crystallin denaturation, leading to variable degrees of vision loss and poor quality of life. Although crystallin denaturation is the primary pathological basis of cataract, oxidative stress and inflammation also play significant roles.Results
It was first confirmed that nattokinase (NK) could degrade cataractous tissue and alleviate the opacification using human cataract phacoemulsification fluid, thus supporting the in vivo anti-cataract efficacy of NK-based nanocomposites (NNs). Herein, we developed minimalist NNs as eye drops, through electrostatic self-assembly between NK and natural macromolecules. The NNs exert three-pronged therapeutic effects (antioxidant, anti-inflammatory, and anti-crystallin denaturation) that disrupt the pathological cycle in cataract. The in vitro cellular studies demonstrated that the NNs were internalized via receptor-mediated endocytosis and micropinocytosis, and efficiently achieved a synergistic scavenging effect of reactive oxygen species (ROS). In ultraviolet B (UVB)-induced cataract mice, the NNs successfully suppressed oxidative stress and inflammation, while protecting crystallins through enhanced intracorneal retention, ultimately ameliorating lens opacity index. Moreover, further analysis revealed that NNs effectively inhibited ROS accumulation by up to 15.78-fold, along with the ROS/NLRP3/pyroptosis axis and the denaturation of crystallins, thereby offering new insights into therapeutic regimens for cataract.Conclusions
Consequently, the NNs alleviated lens opacification by breaking the cataract vicious cycle through a three-pronged inhibition of oxidative stress, inflammation, and crystallin denaturation. Our findings pave the way for utilizing NNs as a novel strategy for reversing cataract, as well as associated ocular disorders.