Document Detail


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
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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
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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


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