HIF1 signaling pathway involving iNOS, COX2 and caspase9 mediates the neuroprotection provided by erythropoietin in the retina of chronic ocular hypertension rats

Abstract

This study aimed to investigate the impacts of erythropoietin (EPO) on the electroretinogram bwave (ERGb), and on the mRNA and protein expression levels of hypoxiainducible factor1 (HIF1), inducible nitric oxide synthase (iNOS), cyclooxygenase2 (COX2) and caspase9 in chronic ocular hypertension rats. Episcleral vein cauterization (EVC) was used to establish the chronic ocular hypertension rat model based on the intraocular pressure (IOP) value. ERGb and mRNA and protein expression levels of HIF1, iNOS, COX2 and caspase9 in normal, EVCtreated and EVC combined with EPO (EVC+EPO)treated rats were measured by electroretinography, RTPCR and western blotting, respectively. Moreover, the correlations of HIF1? with IOP, ERGb, iNOS, COX2 and caspase9 were evaluated. The mRNA and protein expression levels of HIF1, iNOS, COX2 and caspase9 in EVCtreated rats were increased significantly compared with normal rats. The peak expression levels of HIF1, iNOS, COX2 and caspase9 were respectively obtained 7, 7, 7 and 14 days postoperatively. Compared with EVCtreated rats, EPO administration weakened the mRNA and protein expression levels of HIF1, iNOS, COX2 and caspase9. The mRNA expression level of HIF1 demonstrated a significant positive correlation with IOP and ERGb. HIF1 was positively correlated with iNOS, COX2 and caspase9 at the mRNA and protein levels. The protective effect of EPO on the retina of chronic ocular hypertension rats may be mediated by the HIF1 signaling pathway involving iNOS, COX2 and caspase9.