Silica-Coated Gold Nanoparticles Attenuate High Glucose-Induced Oxidative Stress-Mediated Inflammation and Apoptosis in RGC-5 Cells

Background: Oxidative stress is crucial for the morbidity of diabetic complications. An abnormal metabolic milieu as a result of hyperglycemia leads to the onset of several complications, including diabetic retinopathy (DR). Treating eye diseases like DR is challenging due to the eye’s anatomy, physiology, and biochemistry. A biological antioxidant capable of inhibiting oxidative/nitrosative stress-mediated diabetic progression during hyperglycemia is still needed. We investigated the role of silica-coated gold nanoparticles (AuNP@SiO 2 ) on high-glucose (HG)-induced oxidative stress, mitochondrial dysfunction, apoptosis, inflammation, and neurodegeneration in rat retinal ganglion cells (RGC-5). Methodology: Using advanced techniques, we investigated the profound inhibitory effect of AuNP@SiO 2 in RGC-5 cells in the presence of a HG environment. Results: Overproduction of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in the HG environment weakened the endogenous antioxidants, including catalase, superoxide dismutase, and glutathione peroxidase and AuNP@SiO 2 treatment restored the HG effect. Furthermore, excess accumulation of ROS/RNS was allied with mitochondrial dysfunction, characterized by loss of mitochondrial membrane potential (ΔΨm) and increased mitochondrial mass in the HG environment, which Au@SiO 2 nanoparticles (NPs) attenuated in RGC-5 cells. Moreover, the imbalance between the generation of ROS/RNS and their corresponding weakened endogenous antioxidant defense system leads to biomolecule damage, downregulation of 8-oxo guanine glycosylase, and accumulation of deoxyguanosine (8-OHdG) in DNA. However, treatment of AuNP@SiO 2 attenuated the action. To broaden the knowledge, we further investigated the influence of AuNP@SiO 2 on HG-induced increased expression of inflammatory mediators and neurodegenerative markers, leading to apoptosis, which was attenuated by Au@SiO 2 NPs in RGC-5 cells. Conclusion: In summary, AuNP@SiO 2 represents a potentially promising agent for facilitating defense against HG-induced oxidative/nitrosative stress, antioxidant depletion, mitochondrial dysfunction, apoptosis, and inflammation, thus generating a sustained control over ROS/RNS, which consequently evoke the potential of AuNP@SiO 2 as an economic therapeutic remedy in diabetic treatments and its complications.