| First Author | Hoppe G | Year | 2014 |
| Journal | Am J Pathol | Volume | 184 |
| Issue | 6 | Pages | 1890-9 |
| PubMed ID | 24731446 | Mgi Jnum | J:211093 |
| Mgi Id | MGI:5573116 | Doi | 10.1016/j.ajpath.2014.02.017 |
| Citation | Hoppe G, et al. (2014) Inducing a visceral organ to protect a peripheral capillary bed: stabilizing hepatic HIF-1alpha prevents oxygen-induced retinopathy. Am J Pathol 184(6):1890-9 |
| abstractText | Activation of hypoxia-inducible factor (HIF) can prevent oxygen-induced retinopathy in rodents. Here we demonstrate that dimethyloxaloylglycine (DMOG)-induced retinovascular protection is dependent on hepatic HIF-1 because mice deficient in liver-specific HIF-1alpha experience hyperoxia-induced damage even with DMOG treatment, whereas DMOG-treated wild-type mice have 50% less avascular retina (P < 0.0001). Hepatic HIF stabilization protects retinal function because DMOG normalizes the b-wave on electroretinography in wild-type mice. The localization of DMOG action to the liver is further supported by evidence that i) mRNA and protein erythropoietin levels within liver and serum increased in DMOG-treated wild-type animals but are reduced by 60% in liver-specific HIF-1alpha knockout mice treated with DMOG, ii) triple-positive (Sca1/cKit/VEGFR2), bone-marrow-derived endothelial precursor cells increased twofold in DMOG-treated wild-type mice (P < 0.001) but are unchanged in hepatic HIF-1alpha knockout mice in response to DMOG, and iii) hepatic luminescence in the luciferase oxygen-dependent degradation domain mouse was induced by subcutaneous and intraperitoneal DMOG. These findings uncover a novel endocrine mechanism for retinovascular protection. Activating HIF in visceral organs such as the liver may be a simple strategy to protect capillary beds in the retina and in other peripheral tissues. |
