Generation of transgenic mice with mild and severe retinal neovascularisation
Generation of transgenic mice with mild and severe retinal neovascularisation
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DOI：
10.1136/bjo.2004.059089
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发表时间：
2005-07-01
影响因子：
4.1
通讯作者：
Rakoczy, EP
中科院分区：
文献类型：
--
作者：
Lai, CM;Dunlop, SA;Rakoczy, EP
目的：方法：通过显微注射含有人VEGF（165）（hVEGF）基因的DNA构建体（由截短的小鼠视紫红质启动子驱动），构建转基因小鼠模型。小鼠眼睛的特点是临床和组织学和眼部hVEGF水平测定ELISA.Results：表达低hVEGF水平的一个转基因系表现出轻微的临床变化，如局灶性荧光素渗漏，微动脉瘤，静脉迂曲，毛细血管非灌注和轻微的新生血管形成，保持稳定到3个月出生后。在组织学上，有一些干扰和内外核层变薄，偶尔有新血管形成的局灶性区域。相比之下，其他三个线表达高hVEGF水平，同时严重的表型。除了上述，临床特征包括广泛的新生血管形成，出血，视网膜脱离;组织学上，局灶性广泛的区域新生血管形成与视网膜褶皱，细胞损失的内部和外部核层，部分视网膜detachment是常见的。结论：作者产生了四个hVEGF过表达转基因小鼠品系的表型范围从轻度到严重的新生血管形成。这些模型是研究过量VEGF相关分子和细胞变化的有价值的研究工具，并为测试抗血管生成疗法提供了额外的机会。
Aim: To generate a mouse model for slow progressive retinal neovascularisation through vascular endothelial growth factor ( VEGF) upregulation.Methods: Transgenic mice were generated via microinjection of a DNA construct containing the human VEGF(165) (hVEGF) gene driven by a truncated mouse rhodopsin promoter. Mouse eyes were characterised clinically and histologically and ocular hVEGF levels assayed by ELISA.Results: One transgenic line expressing low hVEGF levels showed mild clinical changes such as focal fluorescein leakage, microaneurysms, venous tortuosity, capillary non-perfusion and minor neovascularisation, which remained stable up to 3 months postnatal. Histologically, there were some disturbance and thinning of inner and outer nuclear layers, with occasional focal areas of neovascularisation. By contrast, three other lines expressing high hVEGF levels presented with concomitantly severe phenotypes. In addition to the above, clinical features included extensive neovascularisation, haemorrhage, and retinal detachment; histologically, focal to extensive areas of neovascularisation associated with retinal folds, cell loss in the inner and outer nuclear layers, and partial retinal detachment were common.Conclusions: The authors generated four hVEGF overexpressing transgenic mouse lines with phenotypes ranging from mild to severe neovascularisation. These models are a valuable research tool to study excess VEGF related molecular and cellular changes and provide additional opportunities to test anti-angiogenic therapies.