RETRACTED ARTICLE: Antioxidative effects of polypyrimidine tract-binding protein-associated splicing factor against pathological retinal angiogenesis through promotion of mitochondrial function

Inhibition of APE1/Ref-1 for Neovascular Eye Diseases: From Biology to Therapy

“…The retina’s high energy demand and metabolic rate makes it particularly prone to reactive oxygen species (ROS) accumulation, thereby contributing to oxidative stress and development of retinopathies [ 142 , 143 ]. ROS are implicated in the process of angiogenesis, as the elevation of ROS production and insufficient ROS scavenging result in the elevation of superoxide anion and hydrogen peroxide levels.…”

“…In addition, hyperglycemia, hyperlipidemia and inflammation, three hallmarks of diabetes, stimulate the production of ROS and further contribute to the development of DR [ 142 , 146 ]. Not only are ROS involved in the induction of oxidative stress, but ROS can also mediate angiogenesis and inflammation by inducing VEGF expression, HIF-1α signaling and activating the JAK/STAT pathway [ 143 ]. Clearly, oxidative stress can adversely affect vision and contribute to the development of many retinopathies.…”

“…Nuclear factor erythroid-2-related factor 2 (Nrf2) is a protective transcription factor that is upregulated in response to oxidative stress. Following the induction of oxidative stress, the reduction of cysteine residue 151 of Keap1 allows for Nrf2 to dissociate from Keap1 and enter the nucleus to activate antioxidant response element (ARE) genes, which protect the cell from oxidative stress [ 142 , 143 , 149 ]. The activation of Nrf2 also prevents the overproduction of pro-inflammatory cytokines such as IL-6 and IL-1β [ 150 ].…”

“…The activation of Nrf2 also prevents the overproduction of pro-inflammatory cytokines such as IL-6 and IL-1β [ 150 ]. Previous studies have suggested that the PI3K/Akt and ERK pathways are implicated in the modulation of Nrf2 expression [ 143 , 151 ]. Specifically, in the retina, Nrf2 has been implicated as an important cytoprotective mechanism in response to oxidative stress and may be a potential pharmacological target for retinal diseases [ 152 , 153 ].…”

“…HO-1 is an Nrf2-regulated gene that catalyzes the degradation of heme and is upregulated in response to oxidative stress to protect cells from ROS accumulation [ 151 ]. The induction of HO-1 in response to Nrf2 signaling induces anti-inflammatory effects and can lead to the inhibition of NF-κB signaling; evidence suggests that the ERK and PI3K signaling pathways participate in regulating HO-1 expression [ 143 , 149 , 155 ]. In the retina, protection from oxidative damage can be aided via upregulation of HO-1 [ 143 ].…”