VEGF isoforms and their expression after a single episode of hypoxia or repeated fluctuations between hyperoxia and hypoxia: relevance to clinical ROP.

摘要: PURPOSE Fluctuations in oxygen are associated with the development of severe retinopathy prematurity (ROP) humans. However, causal relationships between variability and ROP remain unknown. We investigated whether isoforms vascular endothelial growth factor (VEGF) were differentially stimulated by hypoxia repeated fluctuations hyperoxia, expressed association intravitreous neovascularization. also determined pigment epithelium-derived (PEDF) was dysregulated perhaps contributing to a delay normal retinal development. METHODS used 50/10 oxygen-induced (50/10 OIR) model that exposes newborn rat pups cycles 24 h 50% alternating 10% cause condition similar human ROP. Animals euthanized at postnatal day 2 (P2; after one cycle 50/10% oxygen), P7 (after 3.5 P14 seven oxygen). Room air raised control exposed single episode assayed immediately afterwards. Retinal VEGF PEDF measured RT-PCR. Total protein ELISA. RESULTS found hyperoxia caused greater expression compared than did hypoxia. VEGF164 mRNA had fold change over other isoforms, VEGF188 VEGF120, degree regardless stimulus or oxygen. predominant isoform time maximal elevated OIR P7, experimental group P18, when neovascularization occurred. CONCLUSIONS Repeated results pathologic isoform, VEGF164, does alone. upregulated an equivalent increased early may play role observed vascularization. These findings provide insight into effect on preterm infants.