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