title: Apolipoprotein E2 and E3, but Not E4, Promote Retinal Pathologic Neovascularization.
abstract: To determine the relationship between the different isoforms of apolipoprotein E (ApoE) and retinal neovascularization.
  
  
  
  The concentrations of ApoE and VEGF in vitreous humor samples with either a macular hole (MH), or diabetic macular edema (DME), or proliferative diabetic retinopathy (PDR) with or without intravitreal injection of bevacizumab (IVB) were measured by ELISA. The effects of each isoform of ApoE on human retinal microvascular endothelial cells (HRMECs) in culture or on the retina of oxygen-induced retinopathy (OIR) mice were investigated.
  
  
  
  The concentrations of ApoE and VEGF were significantly higher in the vitreous humor of patients with PDR and DME than in patients with an MH. There was a significant positive correlation between the concentrations of ApoE and VEGF in vitreous humor of patients. In vitro assays showed that ApoE2 and ApoE3, but not ApoE4, promoted the VEGF-induced cell proliferation and migration. In vivo assays showed that intravitreal injections of ApoE2 and ApoE3 increased the number and area of nodes in the retina of OIR mice. Moreover, ApoE was expressed in the vascular endothelial cell in both normal and OIR retinas, but their expression levels were different at postnatal day (P) 12 and P17.
  
  
  
  These results demonstrate that ApoE2 and ApoE3, but not ApoE4, have proangiogenic effects, and the increased expression of ApoE in the vitreous humor of patients with PDR and DME indicates that ApoE2 and ApoE3 are involved in the development of retinal neovascularization in eyes.
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Masuda
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Shimazawa
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Yuhei
authors.initials: Y
authors.lastname: Hashimoto
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kojima
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Nakamura
authors.affiliation: Department of Ophthalmology, Gifu University School of Medicine, Gifu, Japan.
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Suemori
authors.affiliation: Department of Ophthalmology, Gifu University School of Medicine, Gifu, Japan.
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Mochizuki
authors.affiliation: Department of Ophthalmology, Gifu Municipal Hospital, Gifu, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kawakami
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan 2Department of Ophthalmology, Gifu University School of Medicine, Gifu, Japan.
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Kawase
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hara
mesh_terms: D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D001057:Apolipoproteins E / Q000494:pharmacology / Q000502:physiology*; D000068258:Bevacizumab / Q000627:therapeutic use; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D003930:Diabetic Retinopathy; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D058449:Intravitreal Injections; D008269:Macular Edema / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009389:Neovascularization, Pathologic / Q000378:metabolism; D020033:Protein Isoforms / Q000494:pharmacology / Q000502:physiology; D012160:Retina / Q000187:drug effects / Q000378:metabolism; D015861:Retinal Neovascularization / Q000188:drug therapy / Q000378:metabolism*; D012167:Retinal Perforations / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014822:Vitreous Body / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D001057:Apolipoproteins E; D020033:Protein Isoforms; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab