title: Phosphatidylserine (PS) Is Exposed in Choroidal Neovascular Endothelium: PS-Targeting Antibodies Inhibit Choroidal Angiogenesis In Vivo and Ex Vivo.
abstract: OBJECTIVE
  Choroidal neovascularization (CNV) accounts for 90% of cases of severe vision loss in patients with advanced age-related macular degeneration. Identifying new therapeutic targets for CNV may lead to novel combination therapies to improve outcomes and reduce treatment burden. Our goal was to test whether phosphatidylserine (PS) becomes exposed in the outer membrane of choroidal neovascular endothelium, and whether this could provide a new therapeutic target for CNV.
  
  
  METHODS
  Choroidal neovascularization was induced in C57BL/6J mice using laser photocoagulation. Choroidal neovascularization lesions costained for exposed PS and for intercellular adhesion molecule 2 (or isolectin B4) were imaged in flat mounts and in cross sections. The laser CNV model and a choroidal sprouting assay were used to test the effect of PS-targeting antibodies on choroidal angiogenesis. Choroidal neovascularization lesion size was determined by intercellular adhesion molecule 2 (ICAM-2) staining of flat mounts.
  
  
  RESULTS
  We found that PS was exposed in CNV lesions and colocalized with vascular endothelial staining. Treatment with PS-targeting antibodies led to a 40% to 80% reduction in CNV lesion area when compared to treatment with a control antibody. The effect was the same as that seen using an equal dose of an anti-VEGF antibody. Results were confirmed using the choroid sprouting assay, an ex vivo model of choroidal angiogenesis.
  
  
  CONCLUSIONS
  We demonstrated that PS is exposed in choroidal neovascular endothelium. Furthermore, targeting this exposed PS with antibodies may be of therapeutic value in CNV.
authors.affiliation: Department of Ophthalmology University of Texas Southwestern Medical Center, Dallas, Texas, United States 2Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of Chi.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Ophthalmology University of Texas Southwestern Medical Center, Dallas, Texas, United States.
authors.forename: Bogale
authors.initials: B
authors.lastname: Aredo
authors.affiliation: Department of Ophthalmology University of Texas Southwestern Medical Center, Dallas, Texas, United States 3Department of Ophthalmology, Hainan Provincial People's Hospital, Haikou, Hainan, People's Republic of China.
authors.forename: Kaiyan
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Ophthalmology University of Texas Southwestern Medical Center, Dallas, Texas, United States.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhong
authors.affiliation: Departments of Ophthalmology and Molecular Medicine, Mayo Clinic, Rochester, Minnesota, United States.
authors.forename: Jose S
authors.initials: JS
authors.lastname: Pulido
authors.affiliation: Departments of Cell and Molecular Biology and Ophthalmology, Tulane University, New Orleans, Louisiana, United States.
authors.forename: Shusheng
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Ophthalmology University of Texas Southwestern Medical Center, Dallas, Texas, United States.
authors.forename: Yu-Guang
authors.initials: YG
authors.lastname: He
authors.affiliation: Department of Pharmacology and the Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas, United States.
authors.forename: Xianming
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Pharmacology and the Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas, United States 7Department of Surgery, University of Texas Southwestern Medical Center, Dallas, Texas, United.
authors.forename: Rolf A
authors.initials: RA
authors.lastname: Brekken
authors.affiliation: Department of Ophthalmology University of Texas Southwestern Medical Center, Dallas, Texas, United States.
authors.forename: Rafael L
authors.initials: RL
authors.lastname: Ufret-Vincenty
mesh_terms: D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D020256:Choroidal Neovascularization / Q000188:drug therapy / Q000276:immunology / Q000473:pathology*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D010718:Phosphatidylserines / Q000276:immunology* / Q000378:metabolism
chemical_list: D000906:Antibodies; D010718:Phosphatidylserines