Hypoxia inducible factor-1alpha is increased in ischemic retina: temporal and spatial correlation with VEGF expression.

作者: Peter A. Campochiaro , Gregg L. Semenza , Donald J. Zack , Sean F. Hackett , Hiroaki Ozaki

DOI:

关键词: Inner nuclear layerRetinaVascular endothelial growth factor ABiologyVascular endothelial growth factorAnatomyIschemiaRetinalAndrologyIn situ hybridizationOxygen homeostasis

摘要: PURPOSE Hypoxia inducible factor-1 (HIF-1) is a transcription factor composed of HIF-1alpha and HIF-1beta subunits. HIF-1 transactivates multiple genes whose products play key roles in oxygen homeostasis, including vascular endothelial growth (VEGF). This study was designed to determine whether levels are increased ischemic retina there correlation with expression VEGF. METHODS C57BL/6J mice were killed at time points that span retinal development (PO adult), or on postnatal day (P) 7 they placed 75% environment for 5 days then removed room air after 0, 2, 6, 24 hours 14 days. Eyes frozen, retinas isolated used immunoblot analysis, eyes sectioned immunohisto chemical staining HIF-1beta, situ hybridization RESULTS Immunoblots lysates showed low PO markedly P4, remained high throughout the period decreased an intermediate level adults. relatively constant all points. In oxygen-induced retinopathy, retina. The peak increase occurred 2 hours, returned baseline by hours. Immunohistochemistry hypoxic inner retina, but not normoxic outer There no modulation levels. constitutive VEGF mRNA nuclear layer 6 onset hypoxia elevated several CONCLUSIONS show temporal spatial These findings consistent hypothesis plays role upregulation

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