PURPOSE: To study NAD(P)H oxidase-dependent outcomes after oxygen stresses that are similar to those experienced by preterm infants today using a rat model of retinopathy of prematurity. METHODS: Within 4 hours of birth, pups and their mothers were cycled between 50% and 10% oxygen daily for 14 days and were returned to room air (21% O2, 50/10 oxygen-induced retinopathy [OIR]) or supplemental oxygen (28% O2, 50/10 OIR+SO) for 4 days. Pups received intraperitoneal injections of the specific NAD(P)H oxidase inhibitor apocynin (10 mg/kg/d) or of PBS from postnatal day (P)12 to P17, and some received intraperitoneal injections of hypoxyprobe before kill. Intravitreous neovascularization (IVNV), avascular/total retinal areas, vascular endothelial growth factor (VEGF), NAD(P)H oxidase activity, or hypoxic retina (conjugated hypoxyprobe) were determined in neurosensory retinas. Human retinal microvascular endothelial cells (RMVECs) treated with apocynin or control were exposed to 1% or 21% O2 and assayed for phosphorylated (p-)Janus kinase (JNK) and NAD(P)H oxidase activity. RESULTS: Retinas from 50/10 OIR+SO had increased NAD(P)H oxidase activity and lower VEGF than did retinas from 50/10 OIR. Apocynin treatment reduced the IVNV area and hypoxic retina in 50/10 OIR+SO. RMVECs treated with 1% O2 had increased p-JNK compared with RMVECs exposed to room air. CONCLUSIONS: Different oxygen stresses activate NAD(P)H oxidase to varying degrees to trigger disparate pathways (angiogenesis or apoptosis). The oxygen stresses and outcomes used in this study are relevant to human ROP and may explain some of the complexity in the pathophysiology of ROP resulting from oxygen exposure.
PURPOSE: To study NAD(P)H oxidase-dependent outcomes after oxygen stresses that are similar to those experienced by preterm infants today using a rat model of retinopathy of prematurity. METHODS: Within 4 hours of birth, pups and their mothers were cycled between 50% and 10% oxygen daily for 14 days and were returned to room air (21% O2, 50/10 oxygen-induced retinopathy [OIR]) or supplemental oxygen (28% O2, 50/10 OIR+SO) for 4 days. Pups received intraperitoneal injections of the specific NAD(P)H oxidase inhibitor apocynin (10 mg/kg/d) or of PBS from postnatal day (P)12 to P17, and some received intraperitoneal injections of hypoxyprobe before kill. Intravitreous neovascularization (IVNV), avascular/total retinal areas, vascular endothelial growth factor (VEGF), NAD(P)H oxidase activity, or hypoxic retina (conjugated hypoxyprobe) were determined in neurosensory retinas. Human retinal microvascular endothelial cells (RMVECs) treated with apocynin or control were exposed to 1% or 21% O2 and assayed for phosphorylated (p-)Janus kinase (JNK) and NAD(P)H oxidase activity. RESULTS: Retinas from 50/10 OIR+SO had increased NAD(P)H oxidase activity and lower VEGF than did retinas from 50/10 OIR. Apocynin treatment reduced the IVNV area and hypoxic retina in 50/10 OIR+SO. RMVECs treated with 1% O2 had increased p-JNK compared with RMVECs exposed to room air. CONCLUSIONS: Different oxygen stresses activate NAD(P)H oxidase to varying degrees to trigger disparate pathways (angiogenesis or apoptosis). The oxygen stresses and outcomes used in this study are relevant to human ROP and may explain some of the complexity in the pathophysiology of ROP resulting from oxygen exposure.
Authors: Mohamed Al-Shabrawey; Manuela Bartoli; Azza B El-Remessy; Daniel H Platt; Sue Matragoon; M Ali Behzadian; Robert W Caldwell; Ruth B Caldwell Journal: Am J Pathol Date: 2005-08 Impact factor: 4.307
Authors: Narasimham L Parinandi; Michael A Kleinberg; Peter V Usatyuk; Rhett J Cummings; Arjun Pennathur; Arturo J Cardounel; Jay L Zweier; Joe G N Garcia; Viswanathan Natarajan Journal: Am J Physiol Lung Cell Mol Physiol Date: 2002-07-26 Impact factor: 5.464
Authors: Toshihiko Ueda; Takako Ueda; Shohei Fukuda; Richard Browne; Edwin Jenis; Robert Spengler; Richard Chou; Peter Buch; Ahmad Aljada; Paresh Dandona; R. Sasisekharan; C. Kathleen Dorey; Donald Armstrong Journal: Angiogenesis Date: 1998 Impact factor: 9.596
Authors: Janet R McColm; Steve Cunningham; Jean Wade; Kofi Sedowofia; Balazs Gellen; Tarun Sharma; Neil McIntosh; Brian W Fleck Journal: Pediatr Res Date: 2003-10-15 Impact factor: 3.756
Authors: L E Smith; E Wesolowski; A McLellan; S K Kostyk; R D'Amato; R Sullivan; P A D'Amore Journal: Invest Ophthalmol Vis Sci Date: 1994-01 Impact factor: 4.799
Authors: Kip M Connor; John Paul SanGiovanni; Chatarina Lofqvist; Christopher M Aderman; Jing Chen; Akiko Higuchi; Song Hong; Elke A Pravda; Sharon Majchrzak; Deborah Carper; Ann Hellstrom; Jing X Kang; Emily Y Chew; Norman Salem; Charles N Serhan; Lois E H Smith Journal: Nat Med Date: 2007-06-24 Impact factor: 53.440
Authors: Andreas Stahl; Kip M Connor; Przemyslaw Sapieha; Jing Chen; Roberta J Dennison; Nathan M Krah; Molly R Seaward; Keirnan L Willett; Christopher M Aderman; Karen I Guerin; Jing Hua; Chatarina Löfqvist; Ann Hellström; Lois E H Smith Journal: Invest Ophthalmol Vis Sci Date: 2010-06 Impact factor: 4.799
Authors: Alexander Weidemann; Tim U Krohne; Edith Aguilar; Toshihide Kurihara; Norihiko Takeda; Michael I Dorrell; M Celeste Simon; Volker H Haase; Martin Friedlander; Randall S Johnson Journal: Glia Date: 2010-08 Impact factor: 7.452
Authors: Freya M Mowat; Ulrich F O Luhmann; Alexander J Smith; Clemens Lange; Yanai Duran; Sarah Harten; Deepa Shukla; Patrick H Maxwell; Robin R Ali; James W B Bainbridge Journal: PLoS One Date: 2010-06-14 Impact factor: 3.240
Authors: Manabu McCloskey; Haibo Wang; Yanchao Jiang; George Wesley Smith; Jeremy Strange; M Elizabeth Hartnett Journal: Invest Ophthalmol Vis Sci Date: 2013-03-21 Impact factor: 4.799
Authors: Haibo Wang; Zhihong Yang; Yanchao Jiang; John Flannery; Scott Hammond; Tal Kafri; Sai Karthik Vemuri; Bryan Jones; M Elizabeth Hartnett Journal: Invest Ophthalmol Vis Sci Date: 2014-02-04 Impact factor: 4.799