Effect of Eylea on recombinant AAV2-VEGF-induced choroidal neovascularization

Authors:  Jiang Laisheng,  Liao Qin,  Cai Keyang,  Sun Huiye,  Sun Yunxia

DOI: 10.3760/cma.j.issn.2095-0160.2018.08.008
Published 2018-08-10
Cite as Chin J Exp Ophthalmol, 2018,36(8): 608-612.

Abstract

Objective

To evaluate the effect of Eylea (aflibercept) on recombinant adeno-associated virus 2(AAV2)-vascular endothelial growth factor (VEGF)-induced choroidal neovascularization (CNV).

Methods

Two normal cynomolgus monkeys were used in this study.Recombinant AAV2-VEGF was delivered by subretinal injection (60 μl/eye, 7.0×1011 IU/ml) into both eyes for each cynomolgus monkey.Both eyes of one animal were treated with single intravitreal injection of Eylea (50 μl/eye, 40 mg/ml) 3 weeks after AAV2-VEGF injection, and the two eyes of the other animal were untreated.Optical coherence tomography(OCT), electroretinography (ERG), fluorescein angiography (FFA) and ocular photography were conducted.The experiment was approved by the Institutional Animal Care and Use Committee (IACUC) at JOINN Laboratories (Suzhou) (IACUC serial number: ACU15-1112).

Results

OCT showed that subretinal hyperreflective material, retinal edema, choroid edema and local pigment epithelial detachment were found after injection of recombinant AAV2-VEGF.All of those symptoms were relieved after treated with Eylea, but aggravated after 4 weeks treated with Eylea.FFA showed that the area of fluorescein leakage expanded obviously after 2 weeks treated with AAV2-VEGF, and it was observed at the whole of fundus posterior pole at 5 weeks after injection.After 1 week treated with Eylea, the area of fluorescein leakage decreased obviously, but increased gradually after 4 weeks treated with Eylea.ERG results showed that the amplitude of ERG decreased gradually after injection of recombinant AAV2-VEGF.After intravitreal injection of Eylea, the amplitude of ERG increased gradually, but it decreased again after 4 weeks treated with Eylea.

Conclusions

Injection of recombinant AAV2-VEGF is capable of inducing CNV and pathological retinal in cynomolgus monkey.Eylea can prevent the development of clinically relevant CNV, but the effect just lasts for a period.

Key words:

Choroidal neovascularization; Cynomolgus monkey; Retinopathy; Eylea; Recombinant AAV2-VEGF

Contributor Information

Jiang Laisheng
Joinn Laboratories (Suzhou), Taicang 215421, China
Liao Qin
Joinn Laboratories (Suzhou), Taicang 215421, China
Cai Keyang
Joinn Laboratories (Suzhou), Taicang 215421, China
Sun Huiye
Joinn Laboratories (Suzhou), Taicang 215421, China
Sun Yunxia
Joinn Laboratories (Beijing), Beijing 100176, China
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