Apolipoprotein E2 and E3, but Not E4, Promote Retinal Pathologic Neovascularization.

Abstract

Purpose:

To determine the relationship between the different isoforms of apolipoprotein E (ApoE) and retinal neovascularization.

Methods:

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.

Results:

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.

Conclusions:

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: Tomomi Masuda, Masamitsu Shimazawa, Yuhei Hashimoto, Atsushi Kojima, Shinsuke Nakamura, Shinsuke Suemori, Kiyofumi Mochizuki, Hideaki Kawakami, Kazuhide Kawase, Hideaki Hara
• Journal: Investigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 58 Issue 2 Pg. 1208-1217 (02 01 2017) ISSN: 1552-5783 [Electronic] United States
• PMID: 28241308 (Publication Type: Journal Article)

Chemical References

• Angiogenesis Inhibitors
• Apolipoproteins E
• Protein Isoforms
• Vascular Endothelial Growth Factor A
• Bevacizumab

Topics

• Angiogenesis Inhibitors (therapeutic use)
• Animals
• Apolipoproteins E (pharmacology, physiology)
• Bevacizumab (therapeutic use)
• Cell Movement (physiology)
• Cell Proliferation (physiology)
• Diabetic Retinopathy
• Disease Models, Animal
• Endothelial Cells (drug effects, metabolism)
• Female
• Humans
• Intravitreal Injections
• Macular Edema (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Neovascularization, Pathologic (metabolism)
• Protein Isoforms (pharmacology, physiology)
• Retina (drug effects, metabolism)
• Retinal Neovascularization (drug therapy, metabolism)
• Retinal Perforations (metabolism)
• Vascular Endothelial Growth Factor A (metabolism)
• Vitreous Body (metabolism)