Oxygen-induced retinopathy in mice: amplification by neonatal IGF-I deficit and attenuation by IGF-I administration.
In preterms, low serum levels of IGF (IGF-I) correlate with retinopathy of prematurity (ROP). In mice, IGF-I is a prerequisite for normal retinal development. We further explored the link between IGF-I and oxygen-induced retinopathy (OIR). To assess the role of endogenous IGF-I, pups were redistributed into smaller versus larger litters at birth; in one subgroup, we measured body weight and circulating IGF-I; in another, we applied hyperoxia and assessed retinal neovascularization (NV). To screen for the potential role of exogenous IGF-I, we administered a single bolus of rhIGF-I on postnatal day (P) 4 to pups in normal litters, and applied hyperoxia; body weight and IGF-I were measured; maturation and NV were assessed. Neonatal mice in larger litters had a lower body weight than mice in smaller litters; they had lower levels of circulating IGF-I, and developed more OIR (p = 0.002). Mice who had received rhIGF-I, weighed more and had higher endogenous IGF-I levels; they matured faster and developed less OIR (p = 0.00001). These findings in mice are the first to support the notion that higher availability of endogenous or exogenous IGF-I reduces OIR risk, and thus sharpen the perspective that ROP may be preventable by briefly up-regulating IGF-I after birth.
Vanhaesebrouck
Sophie
S
Neonatal Intensive Care Unit, University Hospital Gasthuisberg, Leuven, B-3000, Belgium. sophie.vanhaesebrouck@uzleuven.be
Daniëls
Hans
H
Moons
Lieve
L
Vanhole
Christine
C
Carmeliet
Peter
P
De Zegher
Francis
F
D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight; D006801:Humans; D018496:Hyperoxia / Q000150:complications*; D007231:Infant, Newborn; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage* / Q000172:deficiency*; D051379:Mice; D015861:Retinal Neovascularization / Q000378:metabolism*; D012178:Retinopathy of Prematurity / Q000209:etiology* / Q000378:metabolism*; D018709:Statistics, Nonparametric
D007334:Insulin-Like Growth Factor I