title: HIF‑1 signaling pathway involving iNOS, COX‑2 and caspase‑9 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 b‑wave (ERG‑b), and on the mRNA and protein expression levels of hypoxia‑inducible factor‑1α (HIF‑1α), inducible nitric oxide synthase (iNOS), cyclooxygenase‑2 (COX‑2) and caspase‑9 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. ERG‑b and mRNA and protein expression levels of HIF‑1α, iNOS, COX‑2 and caspase‑9 in normal, EVC‑treated and EVC combined with EPO (EVC+EPO)‑treated rats were measured by electroretinography, RT‑PCR and western blotting, respectively. Moreover, the correlations of HIF‑1α with IOP, ERG‑b, iNOS, COX‑2 and caspase‑9 were evaluated. The mRNA and protein expression levels of HIF‑1α, iNOS, COX‑2 and caspase‑9 in EVC‑treated rats were increased significantly compared with normal rats. The peak expression levels of HIF‑1α, iNOS, COX‑2 and caspase‑9 were respectively obtained 7, 7, 7 and 14 days postoperatively. Compared with EVC‑treated rats, EPO administration weakened the mRNA and protein expression levels of HIF‑1α, iNOS, COX‑2 and caspase‑9. The mRNA expression level of HIF‑1α demonstrated a significant positive correlation with IOP and ERG‑b. HIF‑1α was positively correlated with iNOS, COX‑2 and caspase‑9 at the mRNA and protein levels. The protective effect of EPO on the retina of chronic ocular hypertension rats may be mediated by the HIF‑1 signaling pathway involving iNOS, COX‑2 and caspase‑9.
authors.affiliation: Department of Ophthalmology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Gui
authors.affiliation: Department of Neurosurgery, The People's Hospital of Liaoning Province, Shenyang, Liaoning 110025, P.R. China.
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Ophthalmology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
authors.forename: Dianwen
authors.initials: D
authors.lastname: Gao
authors.affiliation: Department of Ophthalmology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Ophthalmology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China.
authors.forename: Xun
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D002908:Chronic Disease; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004596:Electroretinography; D000068817:Epoetin Alfa; D004921:Erythropoietin / Q000494:pharmacology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D007429:Intraocular Pressure / Q000187:drug effects / Q000502:physiology; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D009798:Ocular Hypertension / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D012160:Retina / Q000201:enzymology / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D011994:Recombinant Proteins; D004921:Erythropoietin; D000068817:Epoetin Alfa; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D053453:Caspase 9