Bim expression in endothelial cells and pericytes is essential for regression of the fetal ocular vasculature

Wang, S; Zaitoun, IS; Johnson, RP; Jamali, N; Gurel, Z; Wintheiser, CM; Strasser, A; Lindner, V; Sheibani, N; Sorenson, CM

Author(s): Wang, S; Zaitoun, IS; Johnson, RP; Jamali, N; Gurel, Z; Wintheiser, CM; Strasser, A; Lindner, V; Sheibani, N; Sorenson, CM;
Details: Publication Year 2017,Volume 12,Issue #5,Page e0178198
Journal Title: PLoS One
Publication Type: Journal Article
Abstract: Apoptosis plays a central role in developmental and pathological angiogenesis and vessel regression. Bim is a pro-apoptotic Bcl-2 family member that plays a prominent role in both developmental and pathological ocular vessel regression, and neovascularization. Endothelial cells (EC) and pericytes (PC) each play unique roles during vascular development, maintenance and regression. We recently showed that germline deletion of Bim results in persistent hyaloid vasculature, increased retinal vascular density and prevents retinal vessel regression in response to hyperoxia. To determine whether retinal vascular regression is attributable to Bim expression in EC or PC we generated mice carrying a conditional Bim allele (BimFlox/Flox) and VE-cadherin-cre (BimEC mice) or Pdgfrb-cre (BimPC mice). BimEC and BimPC mice demonstrated attenuated hyaloid vessel regression and postnatal retinal vascular remodeling. We also observed decreased retinal vascular apoptosis and proliferation. Unlike global Bim -/- mice, mice conditionally lacking Bim in EC or PC underwent hyperoxia-mediated vessel obliteration and subsequent retinal neovascularization during oxygen-induced ischemic retinopathy similar to control littermates. Thus, understanding the cell autonomous role Bim plays in the retinal vascular homeostasis will give us new insight into how to modulate pathological retinal neovascularization and vessel regression to preserve vision.
Publisher: PLOS
Research Division(s): Molecular Genetics Of Cancer
PubMed ID: 28552963
Publisher's Version: https://doi.org/10.1371/journal.pone.0178198
Open Access at Publisher's Site: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0178198
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2017-06-08 11:26:23

Last Modified: 2017-06-26 02:58:27