Rb1/Rbl1/Vhl loss induces mouse subretinal angiomatous proliferation and hemangioblastoma.
JCI Insight
; 4(22)2019 11 14.
Article
en En
| MEDLINE
| ID: mdl-31613797
ABSTRACT
Von Hippel-Lindau (Vhl) protein inhibits hypoxia-inducible factor (Hif), yet its deletion in murine retina does not cause the extensive angiogenesis expected with Hif induction. The mechanism is unclear. Here we show that retinoblastoma tumor suppressor (Rb1) constrains expression of Hif target genes in the Vhl-/- retina. Deleting Rb1 induced extensive retinal neovascularization and autophagic ablation of photoreceptors in the Vhl-/- retina. RNA-sequencing, ChIP, and reporter assays showed Rb1 recruitment to and repression of certain Hif target genes. Activating Rb1 by deleting cyclin D1 induced a partial defect in the retinal superficial vascular plexus. Unexpectedly, removing Vhl suppressed retinoblastoma formation in murine Rb1/Rbl1-deficient retina but generated subretinal vascular growths resembling retinal angiomatous proliferation (RAP) and retinal capillary hemangioblastoma (RCH). Most stromal cells in the RAP/RCH-like lesions were Sox9+, suggesting a Müller glia origin, and expressed Lgals3, a marker of human brain hemangioblastoma. Thus, the Rb family limit Hif target gene expression in the Vhl-/- retina, and removing this inhibitory signal generates new models for RAP and RCH.
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Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neovascularización Retiniana
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Hemangioblastoma
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Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau
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Proteína p107 Similar a la del Retinoblastoma
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Proteínas de Unión a Retinoblastoma
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Año:
2019
Tipo del documento:
Article