Tetrahedral DNA Framework Penetrating Ocular Barrier for Treatment of Retinal Oxidative Stress

Excessive accumulation of reactive oxygen species in the retina is the predominant pathogenic mechanism underlying dry age-related macular degeneration (dAMD). Although antioxidant chemicals have been shown to be effective in reducing ROS levels, their bioavailability and therapeutic efficacy are restricted by ocular barriers. Herein, we developed a tetrahedral framework nucleic acid (tFNA)-based antioxidant drug for the treatment of retinal oxidative stress diseases. By exploiting their penetration capability, these tFNAs penetrated multiple ocular tissues and cellular barriers. These tFNAs protected retinal pigment epithelium cells from glyoxal-induced oxidative stress damage by exerting their intrinsic antioxidant properties through the JNK and AKT pathways upon entering the cells. The subconjunctival administration of tFNAs alleviated structural damage and reduced retinal cell apoptosis in a retinal oxidative stress rat model. These results indicated that tFNAs are a promising therapeutic drug for the treatment of retinal oxidative stress diseases, which sheds light on the development of dAMD therapy.