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持续的眼内血管内皮生长因子中和作用不会影响 Ins2 糖尿病小鼠的视网膜和脉络膜血管。

Sustained intraocular vascular endothelial growth factor neutralisation does not affect retinal and choroidal vasculature in Ins2 diabetic mice.

机构信息

Centre for Experimental Medicine, Queen's University Belfast, Belfast, UK.

出版信息

Diab Vasc Dis Res. 2019 Sep;16(5):440-449. doi: 10.1177/1479164119843092. Epub 2019 Apr 26.

Abstract

The purpose of this study was to understand the influence of sustained intravitreal vascular endothelial growth factor neutralisation on the retinal and choroidal vasculature in diabetic eyes. Ins2 diabetic mice received five intravitreal injections of anti-mouse vascular endothelial growth factor antibody or goat immunoglobulin G (0.2 µg/µL/eye) over a 4-month period. Retinal and choroidal vascular changes were analysed by confocal microscopy of tissue flat-mounts. Retinal gene expression of vascular endothelial growth factor family members (vascular endothelial growth factors A, B, C and D), vascular endothelial growth factor receptors (sVEGFR-1 and VEGFR-2) and tight junctions (claudin 1, 2, 5; occludin and zonula occludens-1) were analysed by quantitative reverse transcription polymerase chain reaction. Vascular endothelial growth factor A and claudin 5 were significantly increased in diabetic retinae. Gene expression was unaffected by anti-vascular endothelial growth factor treatment. The number of acellular vessels was increased in diabetic retinae and reduced following anti-vascular endothelial growth factor treatment. Retinal and choroidal vascular density and area were unaffected by sustained vascular endothelial growth factor neutralisation. Our results suggest that five consecutive intravitreal anti-vascular endothelial growth factor injections do not cause significant vascular changes in the retina and choroid in diabetic and non-diabetic mice.

摘要

本研究旨在探讨持续抑制脉络膜血管内皮生长因子对糖尿病眼视网膜和脉络膜血管的影响。Ins2 糖尿病小鼠在 4 个月内接受了 5 次玻璃体内抗小鼠血管内皮生长因子抗体或山羊免疫球蛋白 G(0.2μg/μL/眼)注射。通过组织平片共聚焦显微镜分析视网膜和脉络膜血管变化。通过定量逆转录聚合酶链反应分析血管内皮生长因子家族成员(血管内皮生长因子 A、B、C 和 D)、血管内皮生长因子受体(sVEGFR-1 和 VEGFR-2)和紧密连接(claudin 1、2、5;occludin 和 zonula occludens-1)的视网膜基因表达。糖尿病视网膜中血管内皮生长因子 A 和 Claudin 5 的表达显著增加。血管内皮生长因子治疗对基因表达没有影响。无细胞血管数量在糖尿病视网膜中增加,并在血管内皮生长因子治疗后减少。视网膜和脉络膜血管密度和面积不受持续血管内皮生长因子中和的影响。我们的结果表明,连续 5 次玻璃体内抗血管内皮生长因子注射不会导致糖尿病和非糖尿病小鼠视网膜和脉络膜的血管发生显著变化。

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