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Related Experiment Video

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A Mouse Model for Laser-induced Choroidal Neovascularization
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WNT7A/B promote choroidal neovascularization.

Joseph B Lin1, Abdoulaye Sene1, Luke A Wiley2

  • 1Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, MO, USA.

Experimental Eye Research
|June 5, 2018
PubMed
Summary

WNT7A and WNT7B promote abnormal blood vessel growth in the eye, contributing to age-related macular degeneration (AMD). Deleting both WNT7A and WNT7B reduced this growth, suggesting WNT signaling as a potential therapeutic target for AMD.

Keywords:
Age-related macular degenerationAngiogenesisChoroidal neovascularizationWNT7AWNT7Bβ-catenin

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Area of Science:

  • Ophthalmology
  • Molecular Biology
  • Genetics

Background:

  • WNT signaling pathway dysregulation is linked to congenital eye disorders and age-related macular degeneration (AMD).
  • Beta-catenin activation in the vascular endothelium of choroidal neovascular membranes suggests WNT's role in promoting pathologic angiogenesis in AMD.

Purpose of the Study:

  • To investigate the specific roles of WNT7A and WNT7B in the pathogenesis of neovascular age-related macular degeneration (AMD).
  • To determine if WNT7A and WNT7B directly promote angiogenesis relevant to AMD.

Main Methods:

  • Assessed the effect of WNT7A and WNT7B on human dermal microvascular endothelial cell proliferation.
  • Evaluated vascular sprouting from mouse choroidal explants in vitro.
  • Generated and analyzed mice deficient in Wnt7a and/or Wnt7b to assess laser-induced choroidal neovascularization (CNV) in vivo.

Main Results:

  • WNT7A and WNT7B significantly increased endothelial cell proliferation and vascular sprouting.
  • Systemic deletion of both Wnt7a and Wnt7b reduced the severity of CNV.
  • Individual deletion of Wnt7a or Wnt7b did not significantly affect CNV severity, indicating redundant roles.

Conclusions:

  • WNT7A and WNT7B exhibit redundant pro-angiogenic functions in vivo, potentially contributing to choroidal neovascularization in AMD.
  • These WNT isoforms represent potential therapeutic targets for neovascular AMD, pending further investigation into their source in CNV.