Delphinidin regulates the NF-κB/AP-1/caspase-3 pathway to protect against apoptosis of retinal photoreceptors under conditions of photochemical damage

Abstract

Retinal photochemical damage (RPD) can be the main cause of various ophthalmic diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa (RP). Patients' vision can be severely impaired in the late stages of these eye diseases. Delphinidin, one of the major functional components of anthocyanins, has shown preventive effects on RPD and ophthalmic diseases induced by RPD, but the underlying mechanisms are complex and unclear. This study investigated the protective effect of delphinidin on photochemically damaged retinal photoreceptors in vivo and in vitro and characterized the underlying mechanisms. In vivo experiments showed that delphinidin downregulated the expression levels of caspase-3, and reduced the apoptosis rate of retinal photoreceptor cells in SD rats, thus protecting the structural integrity of the retina. In vitro experiments showed that delphinidin could maintain the normal ultrastructure of the mitochondrial endoplasmic reticulum membrane, reduce the apoptosis rate caused by light injury and improve the survival rate of light-damaged 661W cells. In addition, we found that delphinidin increased the mRNA and activated protein expression of NF-κB p65, NF-κB p50, and IκBα in photochemically injured 661W cells, and decreased the mRNA and protein expression of AP-1 (c-fos/c-jun) and Caspase-3/-8/-9. Compared with the model group, phospho-NF-κB p65 in delphinidin-treated cells was translocated into the nucleus, and the nuclear phospho-NF-κB p65 expression was increased, while nuclear c-jun expression was decreased. These results suggested that delphinidin resisted RPD-induced apoptosis of retinal photoreceptors by regulating the expression of factors involved in the NF-κB/AP-1/caspase-3 pathway.