The role of VEGF and IGF-1 in a hypercarbic oxygen-inducedretinopathy rat model of ROP

[摘要] Purpose: We have previously described a severe form ofoxygen-induced retinopathy (OIR) in the neonatal rat, analogous to humanretinopathy of prematurity (ROP), where carbon dioxide is added to theinspired environment (hypercarbic OIR). We studied the time course ofemergence and resolution of neovascularization (NV) in normocarbic OIRand hypercarbic OIR and the associated changes in VEGF and IGF-1 mRNAlevels in hypercarbic OIR.Methods: 550 newborn Sprague-Dawley rats were raised in 22 expandedlitters of 25. Beginning at day 1 of life, rats were exposed to 7 dailycycles of hyperoxia (80% O2, 20.5 h) and hypoxia (10% O2,0.5 h) with a gradual return to 80% O2 over 3 h. InspiredCO2 was maintained at 0.2% for 200 rats (normocarbic OIR) and 10%for 100 rats (hypercarbic OIR). Rats were sacrificed after a subsequent5 day room air recovery period. An additional 250 rats raised in roomair served as age matched controls. Retinae from left eyes weredissected and flatmounts were ADPase-stained. The presence and severityof NV was scored in a masked manner. Right eyes in hypercarbic OIRlitters and room air controls were processed for analysis of VEGF andIGF-1 mRNA.Results: In normocarbic OIR, NV started to emerge before room airrecovery began at day 8. It was maximal at day 10 and resolved by day20. In hypercarbic OIR, a similar pattern was seen, with emergence priorto day 8, peak at day 13 and resolution by day 20. In hypercarbic OIR,retinal VEGF mRNA was decreased at day 8 and increased at day 10compared to room air controls, correlating with maximal NV. RetinalIGF-1 mRNA was not increased at any time in hypercarbic OIR compared toroom air controls.Conclusions: Neovascularization resulting from normocarbic OIR orhypercarbic OIR occurs before room air recovery. Retinal VEGF mRNA wasdownregulated and subsequently upregulated prior to maximal NV inhypercarbic OIR. Neovascularization in the hypercarbic OIR model doesnot appear to be associated with increased retinal IGF-1 mRNA.

[学科分类] 生物化学/生物物理