| Prolyl hydroxylase inhibition during hyperoxia prevents oxygen-induced retinopathy. | |
| | |
MedLine Citation:
|
PMID: 19057008 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Oxygen-induced retinopathy (OIR) in the mouse, like the analogous human disease retinopathy of prematurity, is an ischemic retinopathy dependent on oxygen-induced vascular obliteration. We tested the hypothesis that chemically overriding the oxygen-induced downregulation of hypoxia-inducible factor (HIF) activity would prevent vascular obliteration and subsequent pathologic neovascularization in the OIR model. Because the degradation of HIF-1alpha is regulated by prolyl hydroxylases, we examined the effect of systemic administration of a prolyl hydroxylase inhibitor, dimethyloxalylglycine, in the OIR model. Our results determine that stabilizing HIF activity in the early phase of OIR prevents the oxygen-induced central vessel loss and subsequent vascular tortuosity and tufting that is characteristic of OIR. Overall, these findings imply that simulating hypoxia chemically by stabilizing HIF activity during the causative ischemia phase (hyperoxia) of retinopathy of prematurity may be of therapeutic value in preventing progression to the proliferative stage of the disease. |
| | |
Authors:
|
Jonathan E Sears; George Hoppe; Quteba Ebrahem; Bela Anand-Apte |
Related Documents
:
|
2934518 - Myopathies due to enzyme deficiencies. 3182508 - Aerobic power and cardiovascular response to stress. |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2008-12-04 |
Journal Detail:
|
Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 105 ISSN: 1091-6490 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2008 Dec |
Date Detail:
|
Created Date: 2008-12-17 Completed Date: 2009-01-12 Revised Date: 2009-11-18 |
Medline Journal Info:
|
Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
|
Languages: eng Pagination: 19898-903 Citation Subset: IM |
Affiliation:
|
Department of Ophthalmic Research, Cleveland Clinic Lerner College of Medicine, Cleveland Clinic Foundation, Cleveland OH 44195, USA. searsj@ccf.org |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Aerobiosis Amino Acids, Dicarboxylic / administration & dosage* Animals Basic Helix-Loop-Helix Transcription Factors / antagonists & inhibitors, biosynthesis Disease Models, Animal Enzyme Inhibitors / administration & dosage* Erythropoietin / biosynthesis Humans Hypoxia-Inducible Factor 1, alpha Subunit / agonists, antagonists & inhibitors, biosynthesis Infant, Newborn Kidney / metabolism Liver / metabolism Mice Oxygen / toxicity* Procollagen-Proline Dioxygenase / antagonists & inhibitors*, metabolism Retina / metabolism Retinopathy of Prematurity / chemically induced, enzymology, prevention & control* Vascular Endothelial Growth Factor A / biosynthesis |
| Grant Support | |
ID/Acronym/Agency:
|
CA106415/CA/NCI NIH HHS; EY015638/EY/NEI NIH HHS; EY016490/EY/NEI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Amino Acids, Dicarboxylic; 0/Basic Helix-Loop-Helix Transcription Factors; 0/Enzyme Inhibitors; 0/Hif1a protein, mouse; 0/Hypoxia-Inducible Factor 1, alpha Subunit; 0/Vascular Endothelial Growth Factor A; 0/endothelial PAS domain-containing protein 1; 11096-26-7/Erythropoietin; 5262-39-5/oxalylglycine; 7782-44-7/Oxygen; EC 1.14.11.2/Procollagen-Proline Dioxygenase |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Hypoxic pulmonary vasoconstriction does not contribute to pulmonary blood flow heterogeneity in norm...
Next Document: Critical role of ROR-?t in a new thymic pathway leading to IL-17-producing invariant NKT cell differ...