期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 105, 期 50, 页码 19898-19903出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0805817105
关键词
dimethyloxalylglycine; erythropoeitin; hypoxia-inducible factor; retinopathy of prematurity; vascular endothelial growth factor
资金
- Research to Prevent Blindness
- Lew Wasserman Award
- Knights Templar Eye Foundation
- CCF Innovations
- National Institutes of Health [EY016490, CA106415, EY015638]
- American Heart Association [0555235B]
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-1 alpha 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.
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