Angiopoietin-1 Is Required for Vortex Vein and Choriocapillaris Development in Mice

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2 Scopus citations

Abstract

Background: The choroidal vasculature, including the choriocapillaris and vortex veins, is essential for providing nutrients to the metabolically demanding photoreceptors and retinal pigment epithelium. Choroidal vascular dysfunction leads to vision loss and is associated with age-related macular degeneration and the poorly understood pachychoroid diseases including central serous chorioretinopathy and polypoidal choroidal vasculopathy that are characterized by formation of dilated pachyvessels throughout the choroid. Methods: Using neural crest-specific Angpt1 knockout mice, we show that Angiopoietin 1, a ligand of the endothelial receptor TEK (also known as Tie2) is essential for choriocapillaris development and vortex vein patterning. Results: Lacking choroidal ANGPT1, neural crest-specific Angpt1 knockout eyes exhibited marked choriocapillaris attenuation and 50% reduction in number of vortex veins, with only 2 vortex veins present in the majority of eyes. Shortly after birth, dilated choroidal vessels resembling human pachyvessels were observed extending from the remaining vortex veins and displacing the choriocapillaris, leading to retinal pigment epithelium dysfunction and subretinal neovascularization similar to that seen in pachychoroid disease. Conclusions: Together, these findings identify a new role for ANGPT1 in ocular vascular development and demonstrate a clear link between vortex vein dysfunction, pachyvessel formation, and disease.

Original languageEnglish (US)
Pages (from-to)1413-1427
Number of pages15
JournalArteriosclerosis, thrombosis, and vascular biology
Volume42
Issue number11
DOIs
StatePublished - Nov 1 2022

Keywords

  • angiopoietin
  • choriocapillaris
  • pachychoroid
  • polypoidal choroidal vasculopathy
  • vortex vein

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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