Eylea对AAV2-VEGF重组载体诱导的脉络膜新生血管的抑制作用

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

目的探讨Eylea对腺相关病毒2（AAV2）-血管内皮生长因子（VEGF）重组载体诱导的脉络膜新生血管（CNV）的抑制作用。方法眼睛无异常的2只食蟹猴4只眼均进行视网膜下腔注射给予7.0×1011 IU/ml AAV2-VEGF重组载体每只眼60 μl，2只眼在给予AAV2-VEGF重组载体后3周，玻璃体腔注射50 μl/眼、40 mg/ml Eylea眼内注射液；另外2只眼作为对照。视网膜下腔注射后对食蟹猴进行光相干断层扫描（OCT）、眼底照相、荧光素眼底血管造影（FFA）、全视野视网膜电图（ERG）检查。结果OCT检查可见注射AAV2-VEGF重组载体后，注射局部视网膜下有高反射信号物质生成，伴有视网膜及脉络膜水肿增厚、局部视网膜神经感觉层脱离；注射Eylea后视网膜下高反射信号物质、视网膜及脉络膜水肿、局部视网膜神经感觉层脱离等症状开始减轻，注射Eylea后4周症状开始加重。FFA检查可见，注射AAV2-VEGF重组载体后2周眼底荧光素渗漏区域开始明显扩大，至5周时整个后极部均可见荧光素渗漏；注射Eylea后1周眼底荧光素渗漏区域明显减小，注射Eylea后4周于注射后眼底荧光素渗漏区域又逐渐增大。ERG结果显示，注射AAV2-VEGF重组载体后随着时间的延长，ERG振幅渐进性下降；Eylea注射眼随着注射后时间的延长，ERG振幅逐渐升高，注射Eylea后4周时ERG振幅又逐渐下降。结论注射AAV2-VEGF重组载体可引起CNV及视网膜病变；给予Eylea可改善这些症状，但不能持续改善。

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