Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
4025885 | Ophthalmology | 2015 | 11 Pages |
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.
Keywords
STAT3OIRHIFIGFBP3ROPVEGFR1EpoRIGF-1VEGFR2shRNAshort-hairpin RNAROP, Retinopathy of prematurityOxygen-induced retinopathyInsulin growth factor-1hypoxia-inducible factorsVascular endothelial growth factorVascular Endothelial Growth Factor (VEGF)signal transducer and activator of transcription 3Insulin-like growth factor binding protein 3JAKErythropoietin Receptorvascular endothelial growth factor receptor 1vascular endothelial growth factor receptor 2janus-activated kinase
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Authors
M. Elizabeth MD,