Expression of vascular endothelial growth factor and pigment epithelial-derived factor in a rat model of retinopathy of prematurity

摘要

Objective: To determine the effects of oxygen fluctuations onpigment epithelial-derived factor (PEDF) and vascular endothelialgrowth factor (VEGF)/PEDF ratios in a relevant rat model of retinopathyof prematurity (ROP). Methods: The expression of retinal PEDFmRNA and of VEGF and PEDF protein were determined using real-timepolymerase chain reaction or enzyme-linked immunosorbent assays atdifferent postnatal day ages for rat pups raised in room air (RA) or ina rat model mimicking ROP. Statistical outcomes were determined withfactorial analyses of variance. Mean VEGF and PEDF protein levels weredetermined at different ages for rats in the ROP model and forRA-raised rats, and the ratio of VEGF/PEDF protein versus age wasplotted. At postnatal day (P) 14, inner retinal plexus vascularizationhad extended to the ora serrata in pups raised in RA. In the ROP model,avascular retina persisted at P14 and intravitreous neovascularizationdeveloped at P18. Therefore, VEGF and PEDF expression was determined inthe ROP model and in RA-raised rat pups at P14 and P18. Results: Older age was associated withincreased PEDF mRNA (p0.001), PEDF protein (p=0.005), andVEGF protein (p=0.005), and VEGF protein (p0.0001). Exposure tofluctuations of oxygen in the 50/10 oxygen-induced retinopathy modelcompared to RA was associated with increased PEDF mRNA(p=0.0185), PEDF protein (p0.0001), or VEGF protein (p0.0001).The VEGF/PEDF ratio favored angiogenic inhibition (1.0) before butnot on P14, when avascular retina persisted in the ROP model but not inRA. The VEGF/PEDF ratio favored angiogenesis (1.0) at P14 and P 18when intravitreous neovascularization occurred in the ROP model. Conclusions: Increased expression levelsof VEGF and PEDF are associated with older postnatal day age or withexposure to fluctuations in oxygen in the 50/10 oxygen-inducedretinopathy model compared to RA. PEDF protein more closely associateswith avascular retinal features and neovascularization than does VEGFprotein or the VEGF/PEDF in the ROP model. Although PEDF has beenproposed as a potential treatment in ROP, interventional studies usingPEDF in an ROP model to potentially reduce intravitreousneovascularization are required to determine timing, efficiacy, anddose ofPEDF.