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Investigative Ophthalmology & Visual Science
Article . 2017 . Peer-reviewed
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Investigative Ophthalmology & Visual Science
Article
License: CC BY NC ND
Data sources: UnpayWall
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Apolipoprotein E2 and E3, but Not E4, Promote Retinal Pathologic Neovascularization

Authors: Atsushi Kojima; Hideaki Kawakami; Hideaki Hara; Tomomi Masuda; Masamitsu Shimazawa; Kiyofumi Mochizuki; Shinsuke Nakamura; +3 Authors

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.

Keywords

Male, Diabetic Retinopathy, Neovascularization, Pathologic, Endothelial Cells, Angiogenesis Inhibitors, Retinal Neovascularization, Macular Edema, Retina, Bevacizumab, Mice, Inbred C57BL, Disease Models, Animal, Mice, Apolipoproteins E, Cell Movement, Intravitreal Injections, Animals, Humans, Protein Isoforms, Female, Cell Proliferation

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    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    21
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Average
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
21
Top 10%
Average
Top 10%
gold