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Age‐related macular degeneration (AMD) and diabetic retinopathy (DR) are the world's leading causes of blindness. The retinal pigment epithelium (RPE) and vascular endothelial cell exposed to oxidative stress is the major cause of AMD and DR. DJ‐1, an important endogenous antioxidant, its overexpression is considered as a promising antioxidant treatment for AMD and DR. Here, we modified the tetrahedral frame nucleic acids (tFNAs) with DJ‐1 saRNAs as a delivery system, and synthesized a novel nanocomplex (tFNAs‐DJ‐1 saRNAs). In vitro studies show that tFNAs‐DJ‐1 saRNAs can efficiently transfer DJ‐1 saRNAs to human umbilical vein endothelial cells (HUVECs) and ARPE‐19s, and significantly increased their cellular DJ‐1 level. Reactive oxygen species expression in H2O2‐treated HUVECs and ARPE‐19s were decreased, cell viability was enhanced and cell apoptosis were inhibited when tFNAs‐DJ‐1 saRNAs were delivered. Moreover, tFNAs‐DJ‐1 saRNAs preserved mitochondrial structure and function under oxidative stress conditions. In the aspect of molecular mechanism, tFNAs‐DJ‐1 saRNAs activated Erk and Nrf2 pathway, which might contribute to its protective effects against oxidative stress damage. To conclude, this study shows the successfully establishment of a simple but effective delivery system of DJ‐1 saRNAs associated with antioxidant effects in AMD and DR, which may be a promising agent for future treatment in oxidative stress‐related retinal disorders. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the effects and molecular mechanisms of tetrahedral framework nucleic acids‐microRNA22 (tFNAs‐miR22) on inhibiting pathological retinal neovascularization (RNV) and restoring physiological retinal vessels. A novel DNA nanocomplex (tFNAs‐miR22) was synthesised by modifying microRNA‐22 (miR22) through attachment onto tetrahedral frame nucleic acids (tFNAs), which possess diverse biological functions. Cell proliferation, wound healing, and tube formation were employed for in vitro assays to investigate the angiogenic function of cells. Oxygen‐induced retinopathy (OIR) model was utilised to examine the effects of reducing pathological neovascularization (RNV) and inhibiting vascular occlusion in vivo. In vitro, tFNAs‐miR22 demonstrated the ability to penetrate endothelial cells and effectively suppress cell proliferation, tube formation, and migration in a hypoxic environment. In vivo, tFNAs‐miR22 exhibited promising results in reducing RNV and promoting the restoration of normal retinal blood vessels in OIR model through modulation of the Wnt pathway. This study provided a theoretical basis for the further understanding of RNV, and highlighted the innovative and potential of tFNAs‐miR22 as a therapeutic option for ischemic retinal diseases. [ABSTRACT FROM AUTHOR]