Vanhaesebrouck Sophie, Daniëls Hans, Moons Lieve, Vanhole Christine, Carmeliet Peter, De Zegher Francis
Neonatal Intensive Care Unit, University Hospital Gasthuisberg, Leuven, B-3000, Belgium.
Pediatr Res. 2009 Mar;65(3):307-10. doi: 10.1203/PDR.0b013e3181973dc8.
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.
在早产儿中，血清胰岛素样生长因子（IGF-I）水平低与早产儿视网膜病变（ROP）相关。在小鼠中，IGF-I是正常视网膜发育的前提条件。我们进一步探讨了IGF-I与氧诱导性视网膜病变（OIR）之间的联系。为了评估内源性IGF-I的作用，出生时将幼崽重新分配到较小或较大的窝中；在一个亚组中，我们测量了体重和循环中的IGF-I；在另一个亚组中，我们给予高氧并评估视网膜新生血管形成（NV）。为了筛查外源性IGF-I的潜在作用，我们在出生后第4天（P4）给正常窝中的幼崽单次注射重组人IGF-I（rhIGF-I），并给予高氧；测量体重和IGF-I；评估成熟度和NV。较大窝中的新生小鼠体重低于较小窝中的小鼠；它们循环中的IGF-I水平较低，并且发生更多的OIR（p = 0.002）。接受rhIGF-I的小鼠体重更重，内源性IGF-I水平更高；它们成熟更快，发生的OIR更少（p = 0.00001）。小鼠中的这些发现首次支持了内源性或外源性IGF-I的更高可利用性降低OIR风险这一观点，从而强化了ROP可能通过出生后短暂上调IGF-I来预防的观点。
