Effects of brief, clustered versus dispersed hypoxic episodes on systemic and ocular growth factors in a rat model of oxygen-induced retinopathy.
Oxygen fluctuation patterns in preterm infants who develop retinopathy of prematurity (ROP) are varied and poorly represented in animal models. We examined the hypothesis that clustered (CL) episodes of hypoxia during hyperoxia results in a more severe form of oxygen-induced retinopathy (OIR) than dispersed episodes. Rat pups were exposed to alternating cycles of 1) 50% O2 with three CL episodes of 12% O2 every 6 h; or 2) 50% O2 with one episode of 12% O2 every 2 h, for 7 (P7) or 14 (P14) days postnatal age. Pups were killed after hyperoxia, or placed in room air (RA) until P21. RA littermates were killed at P7, P14, and P21. Systemic and ocular vascular endothelial growth factor (VEGF), soluble VEGFR-1 (sVEGFR-1), insulin-like growth factor I (IGF-I), and growth hormone were examined. All hyperoxia-exposed retinas had evidence of neovascularization. Animals in the CL group had a more severe form of OIR at P21 evidenced by vascular tufts, leaky vessels, retinal hemorrhage, and vascular overgrowth. These characteristics were associated with low body weight; high systemic and ocular VEGF; and low systemic and high ocular sVEGFR-1 and IGF-I. These data suggest that preterm infants who experience CL fluctuations in Pao2 during supplemental O2 therapy are at a higher risk for severe ROP.
Coleman
Rebecca J
RJ
Department of Pediatrics, University of California Irvine, Irvine, California 92868, USA.
Beharry
Kay D A
KD
Brock
Romy S
RS
Abad-Santos
Patricia
P
Abad-Santos
Matthew
M
Modanlou
Houchang D
HD
D000818:Animals; D001835:Body Weight; D004195:Disease Models, Animal; D005865:Gestational Age; D013006:Growth Hormone / Q000378:metabolism; D006801:Humans; D018496:Hyperoxia / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D000860:Hypoxia / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D007231:Infant, Newborn; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000378:metabolism* / Q000473:pathology; D015861:Retinal Neovascularization / Q000209:etiology / Q000378:metabolism; D012178:Retinopathy of Prematurity / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D012720:Severity of Illness Index; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism
D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D040281:Vascular Endothelial Growth Factor Receptor-1