Department of Pediatrics, University of California Irvine, Irvine, California 92868, USA.
Pediatr Res. 2011 Feb;69(2):135-41. doi: 10.1203/PDR.0b013e318204e6fa.
Low-serum IGF-I levels at birth is a risk factor for the development of retinopathy of prematurity in extremely LBW infants. We tested the hypothesis that JB1 (an IGF-I analog) prevents oxygen-induced retinopathy in our rat model. Neonatal rats were exposed to 50% oxygen with brief, clustered, hypoxic (12%) episodes from birth to P14. The pups were treated with s.c. injections of 1) JB1 (1 μg/d) on P1, P2, and P3 (JB1x3); 2) JB1 (1 μg/d) on alternate days from P1 to P13 (JB1x7); or 3) equivalent volume saline. Control littermates were raised in room air (RA) with all conditions identical except for inspired O2. Groups were analyzed after hyperoxia/hypoxia (H/H) cycling at P14 or allowed to recover in RA until P21. Systemic and ocular VEGF, soluble VEGFR-1, and IGF-I; retinal vasculature; and gene profile of retinal angiogenesis were assessed. JB1x3 was more effective with associated increases in sVEGFR-1 and decreased retinal pathologies than JB1x7. We conclude that early short-term exposure to systemic JB1 treatment normalizes retinal abnormalities seen with H/H cycling, an effect that may involve sVEGFR-1.
出生时低血清 IGF-I 水平是极低出生体重儿发生早产儿视网膜病变的危险因素。我们检验了 JB1（一种 IGF-I 类似物）是否可以预防我们的大鼠模型的氧诱导性视网膜病变的假说。从出生到 P14，新生大鼠接受 50%氧气暴露，伴有短暂、成群、缺氧（12%）发作。新生鼠在 P1、P2 和 P3 时接受皮下注射 1）JB1（1 μg/d）（JB1x3）；2）从 P1 到 P13 每隔一天接受 JB1（1 μg/d）注射（JB1x7）；或 3）等量生理盐水。对照同窝仔鼠在空气（RA）中饲养，除了吸入的 O2 外，所有条件均相同。在 P14 进行高氧/低氧（H/H）循环后或允许在 RA 中恢复至 P21 时对各组进行分析。评估全身和眼部 VEGF、可溶性 VEGFR-1 和 IGF-I；视网膜血管；以及视网膜血管生成的基因谱。与 JB1x7 相比，JB1x3 更有效，可增加 sVEGFR-1 并减少视网膜病变。我们得出结论，早期短期全身 JB1 治疗可使 H/H 循环引起的视网膜异常正常化，这种作用可能涉及 sVEGFR-1。
