Abstract
Purpose:
Vascular endothelial growth factor (VEGF) is known as a pathological angiogenetic risk factor. The anti-VEGF antibodies are used for the treatment of diabetic retinopathy, but its efficacy is not long-lasting. Recently, it has been reported that Apolipoprotein E (Apo-E) participated in the pathological vascularization. Therefore, we focus on the role of Apo-E in the retinal neovascularization.
Methods:
Proliferation of human retinal microvascular endothelial cells (HRMECs) was assessed in the presence of Apo-E2, -E3, or -E4 with or without VEGF. Apo-E3 was injected into the intravitreal body of the oxygen-induced retinopathy (OIR) model mice at postnatal day 14 (P14) and retinal neovascularization was quantified at P17. The localization and expression of Apo-E in the retina was also evaluated in the OIR model.
Results:
In vitro, Apo-E2 and -E3 significantly further promoted VEGF-induced cell proliferation but Apo-E4 had no effect in HRMECs. In vivo, intravitreous injection of Apo-E3 increased the number of abnormal blood vessels and area on retina in the OIR model mice compared with normal mice. On the other hand, there was no significant difference in avascular area between each group. In addition, Apo-E was colocalized with retinal endothelial cell and the expression of Apo-E in OIR model mice increased more than that in the normal mice.
Conclusions:
These data suggested that Apo-E2 and -E3 promoted the retinal neovascularization and they might become the new therapeutic drug targets.
Keywords: 700 retinal neovascularization •
499 diabetic retinopathy •
706 retinopathy of prematurity