title: Endothelium Expression of Bcl-2 Is Essential for Normal and Pathological Ocular Vascularization.
abstract: Bcl-2 is an anti-apoptotic protein with important roles in vascular homeostasis and angiogenesis. Mice globally lacking Bcl-2 (Bcl-2 -/-) are small in stature and succumb to renal failure shortly after weaning as a result of renal hypoplasia/cystic dysplasia. We have shown that Bcl-2 -/- mice displayed attenuated retinal vascular development and neovascularization. In vitro studies indicated that in addition to modulating apoptosis, Bcl-2 expression also impacts endothelial and epithelial cell adhesion, migration and extracellular matrix production. However, studies delineating the cell autonomous role Bcl-2 expression plays in the endothelium during vascular development, pruning and remodeling, and neovascularization are lacking. Here we generated mice carrying a conditional Bcl-2 allele (Bcl-2Flox/Flox) and VE-cadherin-cre (Bcl-2EC mice). Bcl-2EC mice were of normal stature and lifespan and displayed some but not all of the retinal vascular defects previously observed in global Bcl-2 deficient mice. Bcl-2EC mice had decreased numbers of endothelial cells, decreased retinal arteries and premature primary branching of the retinal vasculature, but unlike the global knockout mice, spreading of the retinal superficial vascular layer proceeded normally. Choroidal neovascularization was attenuated in Bcl-2EC mice, although retinal neovascularization accompanying oxygen-induced ischemic retinopathy was not. Thus, Bcl-2 expression in the endothelium plays a significant role during postnatal retinal vascularization, and pathological choroidal but not retinal neovascularization, suggesting vascular bed specific Bcl-2 function in the endothelium.
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI, 53705, United States of America.
authors.forename: Ismail S
authors.initials: IS
authors.lastname: Zaitoun
authors.affiliation: Department of Pediatrics, University of Wisconsin, Madison, WI, 53705, United States of America.
authors.forename: Ryan P
authors.initials: RP
authors.lastname: Johnson
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI, 53705, United States of America; McPherson Eye Research Institute, University of Wisconsin, Madison, WI, 53705, United States of America.
authors.forename: Nasim
authors.initials: N
authors.lastname: Jamali
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI, 53705, United States of America.
authors.forename: Reem
authors.initials: R
authors.lastname: Almomani
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI, 53705, United States of America.
authors.forename: Shoujian
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Wisconsin, Madison, WI, 53705, United States of America; McPherson Eye Research Institute, University of Wisconsin, Madison, WI, 53705, United States of America.
authors.forename: Nader
authors.initials: N
authors.lastname: Sheibani
authors.affiliation: Department of Pediatrics, University of Wisconsin, Madison, WI, 53705, United States of America; McPherson Eye Research Institute, University of Wisconsin, Madison, WI, 53705, United States of America.
authors.forename: Christine M
authors.initials: CM
authors.lastname: Sorenson
mesh_terms: D000818:Animals; D004730:Endothelium, Vascular / Q000254:growth & development / Q000378:metabolism*; D005123:Eye / Q000098:blood supply; D005260:Female; D051379:Mice; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000502:physiology*; D012160:Retina / Q000378:metabolism; D012171:Retinal Vessels / Q000502:physiology / Q000503:physiopathology
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; C052617:Bcl2 protein, mouse