Signaling pathways triggered by oxidative stress that mediate features of severe retinopathy of prematurity

Abstract

Oxidative stress has been implicated in the pathogenesis of retinopathy of prematurity for decades. It is becoming increasingly understood that reactive oxygen species can trigger signaling pathways that have beneficial or pathologic outcomes. Broad inhibition of reactive oxygen species in the preterm infant may lead to unwanted consequences, as has been experienced with vitamin E studies in the past. In this study, we provide a current understanding of the role of oxidative stress in activating signaling pathways that cause pathologic features in severe retinopathy of prematurity as it manifests in the era of oxygen regulation.

Figure 1

Postnatal oxygen stress induces oxidative stress and nitro-oxidative stress via activation of NADPH oxidase, and eNOS, and via hypoxia-or ROS stabilized HIF1α. (ENOS, nitric oxide synthetase; HIF1α, hypoxia-inducible factor-1 alpha; NADPH oxidase, nicotinamide adenine dinucleotide phosphate; NO, nitric oxide)

Figure 2

Signaling events regulated by stabilized HIF-1a contribute to the pathogenesis of ROP: Avascular retina and Vasoproliferation. (HIF1α, Hypoxia-inducible factor-1 ALPHA; VEGF, vascular endothelial growth factor; STAT3, signaling transducer and activator of transcription 3; EPO, erythropoietin; PRVD, physiologic retinal vascular development)

Figure 3

Signaling events regulated by oxidative stress contribute to the pathogenesis of ROP: Avascular retina and Vasoproliferation. (PLA2, phospholipase A2; COX, cyclooxygenase; PPARγ, peroxisome proliferator-activated receptor gamma; PGS, prostaglandins; PC, prostacyclin; TA, thromboxanes; STAT3, signaling transducer and activator of transcription 3)

Figure 4

Signaling events regulated by nitro-oxidative stress contribute to the pathogenesis of ROP: Avascular retina and Vasoproliferation. (VEGF, vascular endothelial growth factor)