Tetrahedral framework nucleic acids prevent retina ischemia–reperfusion injury from oxidative stress via activating the Akt/Nrf2 pathway
Retinal ischemia–reperfusion (I/R) injuries is involved in the universal pathological process of many ophthalmic disease, including glaucoma, diabetic retinopathy, retinal arterial occlusion, etc. The reason is that ischemia-reperfusion injury is accompanied by abnormal accumulation of reactive oxygen species (ROS), which will cause damage to retinal ganglion cells (RGCs), promote its apoptosis, and finally lead to irreversible loss of visual field. RGCs are specialized projection neurons that are situated in the inner retinal surface of eyes, and they transmit visual image into certain areas of the brain in the form of action potentials. Therefore, any damage that affects the viability of RGCs can cause visual field defects or even irreversible visual loss. There is no effective drug treatment in clinical practice for the loss of visual field that is caused by the oxidation and apoptosis of RGCs. Hence, finding a drug with neuroprotective and antioxidant functions is urgently needed. As a new type of nanomaterial, tetrahedron frame nuclide nanostructures(tFNAs) exhibit outstanding biocompatibility and have been shown in our previous studies to participate in the positive regulation of cell behavior. In this experiment, we first established a cellular model of oxidative stress in RGCs with tert-butyl peroxide (TBHP). Then, we primarily explored the antioxidant and neuroprotective effects of tFNAs after TBHP-induced oxidative stress and the main mechanisms by which tFNAs function. Our research shows that tFNAs can reduce the production of reactive oxygen species (ROS) in cells and protect cells from oxidative stress by regulating intracellular oxidation-related enzymes. In addition, tFNAs can simultaneously significantly improve oxidative stress-induced apoptosis via affecting the expression of apoptosis-related proteins. Finally, we confirmed by Western blotting that the mechanism by which tFNAs prevent damage that is caused by oxidative stress is through activating the Akt/Nrf2 pathway. Our findings provide new ideas for the prevention and treatment for a series of diseases that are caused by oxidative stress to RGCs.