Open AccessBim expression in endothelial cells and pericytes is essential for regression of the fetal ocular vasculature
Author(s) -
Shoujian Wang,
Ismail Zaitoun,
Ryan P. Johnson,
Nasim Jamali,
Zafer Gurel,
Catherine M. Wintheiser,
Andreas Strasser,
Volkhard Lindner,
Nader Sheibani,
Christine M. Sorenson
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0178198
Subject(s) - retinal , neovascularization , biology , angiogenesis , pericyte , retina , pathology , vascular endothelial growth factor a , hyperoxia , cancer research , vascular endothelial growth factor , endothelial stem cell , medicine , neuroscience , lung , genetics , biochemistry , vegf receptors , in vitro
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 (Bim Flox/Flox ) and VE-cadherin-cre (Bim EC mice) or Pdgfrb-cre (Bim PC mice). Bim EC and Bim PC 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.