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

Area of Science:

• Ophthalmology
• Vascular Biology
• Genetics

Background:

• Retinal neovascularization is a hallmark of several sight-threatening eye diseases.
• Apolipoprotein E (ApoE) is a lipid-binding protein with various physiological roles.
• The specific role of ApoE isoforms in retinal neovascularization remains unclear.

Purpose of the Study:

• To investigate the relationship between apolipoprotein E (ApoE) isoforms and retinal neovascularization.
• To determine the proangiogenic potential of different ApoE isoforms in vitro and in vivo.

Main Methods:

• Vitreous humor samples from patients with macular hole, diabetic macular edema, or proliferative diabetic retinopathy were analyzed for ApoE and VEGF concentrations.
• In vitro studies assessed the effects of ApoE isoforms on human retinal microvascular endothelial cells (HRMECs).
• In vivo studies evaluated the impact of ApoE isoforms on retinal neovascularization in oxygen-induced retinopathy (OIR) mouse models.

Main Results:

• Vitreous ApoE and VEGF levels were significantly higher in patients with proliferative diabetic retinopathy (PDR) and diabetic macular edema (DME) compared to those with macular hole (MH).
• ApoE2 and ApoE3, but not ApoE4, enhanced vascular endothelial growth factor (VEGF)-induced proliferation and migration of HRMECs.
• Intravitreal administration of ApoE2 and ApoE3 increased neovascularization in OIR mice, while ApoE4 had no such effect.

Conclusions:

• ApoE2 and ApoE3 exhibit proangiogenic properties, promoting retinal neovascularization.
• Increased ApoE expression in the vitreous humor of patients with PDR and DME suggests a role for ApoE2 and ApoE3 in the pathogenesis of these conditions.