Your browser doesn't support javascript.
loading
WNT7A/B promote choroidal neovascularization.
Lin, Joseph B; Sene, Abdoulaye; Wiley, Luke A; Santeford, Andrea; Nudleman, Eric; Nakamura, Rei; Lin, Jonathan B; Moolani, Harsh V; Apte, Rajendra S.
Afiliación
  • Lin JB; Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, MO, USA.
  • Sene A; Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, MO, USA.
  • Wiley LA; Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, MO, USA; Institute for Vision Research, Department of Ophthalmology & Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
  • Santeford A; Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, MO, USA.
  • Nudleman E; Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, MO, USA.
  • Nakamura R; Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, MO, USA.
  • Lin JB; Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, MO, USA.
  • Moolani HV; Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, MO, USA.
  • Apte RS; Department of Ophthalmology & Visual Sciences, Washington University School of Medicine, St. Louis, MO, USA; Diabetic Cardiovascular Disease Center, Washington University School of Medicine, St. Louis, MO, USA; Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA;
Exp Eye Res ; 174: 107-112, 2018 09.
Article en En | MEDLINE | ID: mdl-29864439
Perturbations in WNT signaling are associated with congenital eye disorders, including familial exudative vitreoretinopathy and Norrie disease. More recently, activation of the WNT pathway has also been shown to be associated with age-related macular degeneration (AMD). In this study, we identified that in choroidal neovascular membranes from AMD patients, ß-catenin is activated specifically in the vascular endothelium, suggesting that WNT promotes pathologic angiogenesis by directly affecting vascular endothelial cells. WNT7B has been shown to be important during eye development for regression of the fetal hyaloid vasculature. However, it has not yet been established whether WNT7A and/or WNT7B are involved in neovascular AMD pathogenesis. Here, we show that WNT7A and WNT7B increase the proliferation of human dermal microvascular endothelial cells in a dose-dependent manner. Both WNT7A and WNT7B also stimulated vascular sprouting from mouse choroidal explants in vitro. To evaluate in vivo relevance, we generated mice systemically deficient in Wnt7a and/or Wnt7b. Genetic deletion of both Wnt7a and Wnt7b decreased the severity of laser injury-induced choroidal neovascularization (CNV), while individual deletion of either Wnt7a or Wnt7b did not have a significant effect on CNV, suggesting that WNT7A and WNT7B have redundant pro-angiogenic roles in vivo. Cumulatively, these findings identify specific WNT isoforms that may play a pathologic role in CNV as observed in patients with neovascular AMD. Although the source of increased WNT7A and/or WNT7B in CNV requires further investigation, WNT signaling may be a potential target for therapeutic intervention if these results are demonstrated to be relevant in human disease.
Asunto(s)
Palabras clave

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neovascularización Coroidal / Proteínas Wnt Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: Exp Eye Res Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neovascularización Coroidal / Proteínas Wnt Tipo de estudio: Prognostic_studies Límite: Animals / Humans / Male Idioma: En Revista: Exp Eye Res Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido