Prolyl hydroxylase inhibition during hyperoxia prevents oxygen-induced retinopathy.
Proc Natl Acad Sci U S A
; 105(50): 19898-903, 2008 Dec 16.
Article
em En
| MEDLINE
| ID: mdl-19057008
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oxigênio
/
Retinopatia da Prematuridade
/
Pró-Colágeno-Prolina Dioxigenase
/
Inibidores Enzimáticos
/
Aminoácidos Dicarboxílicos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
/
Newborn
Idioma:
En
Revista:
Proc Natl Acad Sci U S A
Ano de publicação:
2008
Tipo de documento:
Article
País de afiliação:
Estados Unidos