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Developmental vascular pruning in neonatal mouse retinas is programmed by the astrocytic oxygen-sensing mechanism.
Duan, Li-Juan; Fong, Guo-Hua.
Afiliación
  • Duan LJ; Center for Vascular Biology, University of Connecticut Health Center, Farmington, CT 06030-3501, USA.
  • Fong GH; Center for Vascular Biology, University of Connecticut Health Center, Farmington, CT 06030-3501, USA fong@uchc.edu.
Development ; 146(8)2019 04 17.
Article en En | MEDLINE | ID: mdl-30910827
ABSTRACT
Vascular pruning is crucial for normal development, but its underlying mechanisms are poorly understood. Here, we report that retinal vascular pruning is controlled by the oxygen-sensing mechanism in local astrocytes. Oxygen sensing is mediated by prolyl hydroxylase domain proteins (PHDs), which use O2 as a substrate to hydroxylate specific prolyl residues on hypoxia inducible factor (HIF)-α proteins, labeling them for polyubiquitylation and proteasomal degradation. In neonatal mice, astrocytic PHD2 deficiency led to elevated HIF-2α protein levels, expanded retinal astrocyte population and defective vascular pruning. Although astrocytic VEGF-A was also increased, anti-VEGF failed to rescue vascular pruning. However, stimulation of retinal astrocytic growth by intravitreal delivery of PDGF-A was sufficient to block retinal vascular pruning in wild-type mice. We propose that in normal development, oxygen from nascent retinal vasculature triggers PHD2-dependent HIF-2α degradation in nearby astrocytic precursors, thus limiting their further growth by driving them to differentiate into non-proliferative mature astrocytes. The physiological limit of retinal capillary density may be set by astrocytes available to support their survival, with excess capillaries destined for regression.This article has an associated 'The people behind the papers' interview.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Oxígeno / Retina / Astrocitos Límite: Animals Idioma: En Revista: Development Asunto de la revista: BIOLOGIA / EMBRIOLOGIA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Oxígeno / Retina / Astrocitos Límite: Animals Idioma: En Revista: Development Asunto de la revista: BIOLOGIA / EMBRIOLOGIA Año: 2019 Tipo del documento: Article País de afiliación: Estados Unidos