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An Ex Vivo Choroid Sprouting Assay of Ocular Microvascular Angiogenesis
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COCO/DAND5 inhibits developmental and pathological ocular angiogenesis.

Natalija Popovic1,2, Erika Hooker1,2, Andrea Barabino2,3

  • 1Faculty of Medicine, University of Montreal, Montreal, QC, Canada.

EMBO Molecular Medicine
|February 15, 2021
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Summary

A novel protein, COCO, effectively inhibits pathological ocular angiogenesis, offering a potential new therapy for conditions like age-related macular degeneration (AMD) and retinopathy of prematurity.

Keywords:
COCOangiogenesisenergy metabolismocular pathologies

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Area of Science:

  • Ophthalmology
  • Molecular Biology
  • Angiogenesis Research

Background:

  • Neovascularization drives visual disorders such as age-related macular degeneration (AMD) and retinopathy of prematurity.
  • Current treatments target vascular endothelial growth factor (VEGF), but resistance and side effects like geographic atrophy are concerns.
  • Alternative therapeutic pathways for ocular angiogenesis are crucial.

Purpose of the Study:

  • To identify and characterize a novel inhibitor of pathological ocular angiogenesis.
  • To evaluate the therapeutic potential of COCO in preclinical models of neovascular eye diseases.

Main Methods:

  • In vitro assessment of COCO's effects on endothelial cell proliferation, migration, and sprouting.
  • In vivo studies using intravitreal injections of COCO in models of retinopathy of prematurity and choroidal neovascularization.
  • Mechanistic studies investigating COCO's impact on TGFβ, BMP pathways, cellular metabolism, and redox balance.

Main Results:

  • COCO significantly inhibited endothelial cell sprouting, migration, and proliferation in vitro.
  • Intravitreal COCO administration suppressed retinal vascularization in developmental and retinopathy of prematurity models.
  • COCO effectively reduced angiogenesis in choroidal neovascularization models.
  • Mechanistically, COCO modulated TGFβ and BMP signaling, altered cellular energy metabolism, and affected redox balance.

Conclusions:

  • COCO is a potent inhibitor of both retinal and choroidal angiogenesis.
  • COCO presents a promising therapeutic candidate for neovascular ocular diseases, addressing limitations of current anti-VEGF therapies.