title: Experimental Branch Retinal Vein Occlusion Induces Upstream Pericyte Loss and Vascular Destabilization.
abstract: OBJECTIVE
  Branch retinal vein occlusion (BRVO) leads to extensive vascular remodeling and is important cause of visual impairment. Although the vascular morphological changes following experimental vein occlusion have been described in a variety of models using angiography, the underlying cellular events are ill defined.
  
  
  RESULTS
  We here show that laser-induced experimental BRVO in mice leads to a wave of TUNEL-positive endothelial cell (EC) apoptosis in the upstream vascular network associated with a transient edema and hemorrhages. Subsequently, we observe an induction of EC proliferation within the dilated vein and capillaries, detected by EdU incorporation, and the edema resolves. However, the pericytes of the upstream capillaries are severely reduced, which was associated with continuing EC apoptosis and proliferation. The vascular remodeling was associated with increased expression of TGFβ, TSP-1, but also FGF2 expression. Exposure of the experimental animals to hypoxia, when pericyte (PC) dropout had occurred, led to a dramatic increase in endothelial cell proliferation, confirming the vascular instability induced by the experimental BRVO.
  
  
  CONCLUSIONS
  Experimental BRVO leads to acute endothelial cells apoptosis and increased permeability. Subsequently the upstream vascular network remains destabilized, characterized by pericyte dropout, un-physiologically high endothelial cells turnover and sensitivity to hypoxia. These early changes might pave the way for capillary loss and subsequent chronic ischemia and edema that characterize the late stage disease.
authors.affiliation: INSERM, U968, Paris, F-75012, France; Sorbonne Universités, UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, F-75012, France; CNRS, UMR_7210, Paris, F-75012, France.
authors.forename: Elisa
authors.initials: E
authors.lastname: Dominguez
authors.affiliation: Université François-Rabelais de Tours, CNRS, GICC UMR 7292, Tours, France.
authors.forename: William
authors.initials: W
authors.lastname: Raoul
authors.affiliation: INSERM, U968, Paris, F-75012, France; Sorbonne Universités, UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, F-75012, France; CNRS, UMR_7210, Paris, F-75012, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Calippe
authors.affiliation: INSERM, U968, Paris, F-75012, France; Sorbonne Universités, UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, F-75012, France; CNRS, UMR_7210, Paris, F-75012, France; Centre Hospitalier National d¹Ophtalmologie des Quinze-Vingts, DHU ViewMaintain, INSERM-DHOS CIC 1423, Paris, F-75012, France.
authors.forename: José-Alain
authors.initials: JA
authors.lastname: Sahel
authors.affiliation: INSERM, U968, Paris, F-75012, France; Sorbonne Universités, UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, F-75012, France; CNRS, UMR_7210, Paris, F-75012, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Guillonneau
authors.affiliation: INSERM, U968, Paris, F-75012, France; Sorbonne Universités, UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, F-75012, France; CNRS, UMR_7210, Paris, F-75012, France; Centre Hospitalier National d¹Ophtalmologie des Quinze-Vingts, DHU ViewMaintain, INSERM-DHOS CIC 1423, Paris, F-75012, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Paques
authors.affiliation: INSERM, U968, Paris, F-75012, France; Sorbonne Universités, UPMC Univ Paris 06, UMR_S 968, Institut de la Vision, Paris, F-75012, France; CNRS, UMR_7210, Paris, F-75012, France.
authors.forename: Florian
authors.initials: F
authors.lastname: Sennlaub
mesh_terms: D000818:Animals; D017209:Apoptosis; D049109:Cell Proliferation; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000473:pathology*; D051379:Mice; D020286:Pericytes / Q000473:pathology*; D012170:Retinal Vein Occlusion / Q000209:etiology / Q000473:pathology*; D066253:Vascular Remodeling