Signaling Pathways Triggered by Oxidative Stress That Mediate Features of Severe Retinopathy of Prematurity

Figure 1. Postnatal oxygen stress induces oxidative stress and nitro-oxidative stress via activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and endothelial nitric oxide synthase (eNOS), as well as via hypoxia-stabilized or reactive oxygen species–stabilized hypoxia-inducible factor 1α (HIF1α). ↑ NO indicates increased nitric oxide.

Figure 2. Signaling events regulated by stabilized hypoxia-inducible factor 1α (HIF1a) contribute to the pathogenesis of retinopathy of prematurity by increasing avascular retina in phase 1 and/or vasoproliferation in phase 2. EPO indicates erythropoietin; PRVD, physiologic retinal vascular development; STAT3, signaling transducer and activator of transcription 3; VEGF, vascular endothelial growth factor; ↑, increased; and ↓, decreased.

Figure 3. Signaling events regulated by oxidative stress contribute to the pathogenesis of retinopathy of prematurity by increasing avascular retina in phase 1 and/or vasoproliferation in phase 2. COX indicates cyclooxygenase; PC, prostacyclin; PGS, prostaglandins; PLA2, phospholipase A₂; PPARγ, peroxisome proliferator–activated receptor γ; STAT3, signaling transducer and activator of transcription 3; TA, thromboxanes; and ↑, increased.

Figure 4. Signaling events regulated by nitro-oxidative stress contribute to the pathogenesis of retinopathy of prematurity by increasing avascular retina in phase 1 and/or vasoproliferation in phase 2. VEGF indicates vascular endothelial growth factor; ↑, increased.