The effects of oxygen stresses on the development of features of severe retinopathy of prematurity: knowledge from the 50/10 OIR model.
The objective of this study is to determine growth factor expression and activation of signaling pathways associated with intravitreous neovascularization and peripheral avascular retina using a model of retinopathy of prematurity (ROP) relevant to today with oxygen monitoring in neonatal units. Studies using 50/10 oxygen-induced retinopathy (OIR) and 50/10 OIR+SO models were reviewed. Repeated fluctuations in oxygen increased retinal vascular endothelial growth factor (VEGF) even while peripheral avascular retina persisted and prior to the development of intravitreous neovascularization. Repeated fluctuations in oxygen increased VEGF(164) expression but not VEGF(120). Neutralizing VEGF bioactivity significantly reduced intravitreous neovascularization and arteriolar tortuosity without interfering with ongoing retinal vascularization. Repeated oxygen fluctuations led to retinal hypoxia and increased reactive oxygen species (ROS). Inhibiting ROS with NADPH oxidase inhibitor, apocynin, reduced avascular retina by interfering with apoptosis. Supplemental oxygen reduced retinal VEGF concentration and exacerbated NADPH oxidase activation to contribute to intravitreous neovascularization through activation of the JAK/STAT pathway. Oxygen stresses relevant to those experienced by preterm infants today trigger signaling of different pathways to cause avascular retina and intravitreous neovascularization. Increased signaling of VEGF appears important to the development of both avascular retina and intravitreous neovascularization.
Hartnett
M Elizabeth
ME
Department of Ophthalmology, University of North Carolina, 130 Mason Farm Road, Chapel Hill, NC 27599-7040, USA. hartnet@med.unc.edu
D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007231:Infant, Newborn; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors; D018384:Oxidative Stress; D010100:Oxygen / Q000633:toxicity*; D051381:Rats; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D015861:Retinal Neovascularization / Q000209:etiology / Q000378:metabolism; D012178:Retinopathy of Prematurity / Q000209:etiology* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014822:Vitreous Body / Q000098:blood supply
D000098:Acetophenones; D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; C056165:acetovanillone; D019255:NADPH Oxidases; D010100:Oxygen