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.
SourceAvailable from: Mary Elizabeth Hartnett[Show abstract] [Hide abstract]
ABSTRACT: Retinopathy of prematurity (ROP) is a potentially blinding disorder in premature infants. The underlying pathophysiology is incompletely understood, limiting the prevention and treatment of this devastating condition. Current therapies are directed toward management of aberrant neovascularization thought to result from retinal ischemia in the developing preterm retina. The molecular mediators important for development of retinal ischemia and subsequent neovascular pathology are not fully understood. However, oxygen has been shown to be a key mediator of disease and the oxygen environment for preterm infants has been extensively studied. Despite this, the optimal oxygen environment for preterm infants remains unclear and recent works seeking to clarify this relationship demonstrate somewhat disparate findings. These data further substantiate that ROP is a complex disease with multifactorial etiology including genetic and environmental factors. Therefore, while environmental factors such as oxygen are important to our understanding of the disease process and care of preterm infants, identification of the molecular mediators downstream of oxygen which are necessary for development of ROP pathology will be critical to improve prevention, diagnosis and treatment strategies.Journal of Ophthalmic & Vision Research 01/2014; 9(1):94-100.
05/2014; 44(2):223-226. DOI:10.4274/tjo.33254
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ABSTRACT: Retinopathy of prematurity (ROP) affects only premature infants, but as premature births increase in many areas of the world, ROP has become a leading cause of childhood blindness. Blindness can occur from aberrant developmental angiogenesis that leads to fibrovascular retinal detachment. To treat severe ROP, it is important to study normal developmental angiogenesis and the stresses that activate pathologic signaling events and aberrant angiogenesis in ROP. Vascular endothelial growth factor (VEGF) signaling is important in both physiologic and pathologic developmental angiogenesis. Based on studies in animal models of oxygen-induced retinopathy (OIR), exogenous factors such as oxygen levels, oxidative stress, inflammation, and nutritional capacity have been linked to severe ROP through dysregulated signaling pathways involving hypoxia-inducible factors and angiogenic factors like VEGF, oxidative species, and neuroprotective growth factors to cause phases of ROP. This translational science review focuses on studies performed in animal models of OIR representative of human ROP and highlights several areas: mechanisms for aberrant growth of blood vessels into the vitreous rather than into the retina through over-activation of VEGF receptor 2 signaling, the importance of targeting different cells in the retina to inhibit aberrant angiogenesis and promote physiologic retinal vascular development, toxicity from broad and targeted inhibition of VEGF bioactivity, and the role of VEGF in neuroprotection in retinal development. Several future translational treatments are discussed, including considerations for targeted inhibition of VEGF signaling instead of broad intravitreal anti-VEGF treatment.Ophthalmology 10/2014; 122(1). DOI:10.1016/j.ophtha.2014.07.050 · 6.17 Impact Factor