Human Vascular Endothelial Growth Factor A 165 Expression Induces the Mouse Model of Neovascular Age-Related Macular Degeneration

Vascular endothelial growth factor (VEGF) expression induces age-related macular degeneration (AMD), which is a common vision-threatening disease due to choroidal neovascularization and a fibrovascular membrane. We describe a mouse model of neovascular AMD with the local expression of human VEGF-A i...

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Bibliographic Details
Published inGenes Vol. 9; no. 9
Main Authors Kokki, Emmi, Karttunen, Tommi, Olsson, Venla, Kinnunen, Kati, Ylä-Herttuala, Seppo
Format Journal Article
LanguageEnglish
Published Switzerland 31.08.2018
Subjects
gene transfer
vascular endothelial growth factor
adenovirus
neovascularization
gene therapy
subretinal
animal model
age-related macular degeneration
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Summary:Vascular endothelial growth factor (VEGF) expression induces age-related macular degeneration (AMD), which is a common vision-threatening disease due to choroidal neovascularization and a fibrovascular membrane. We describe a mouse model of neovascular AMD with the local expression of human VEGF-A in the eye. We use a transgenic mouse in which human VEGF-A has been silenced with the loxP-STOP fragment. The choroidal neovascularization and human VEGF-A expression in the mouse are induced by subretinal adenoviral gene delivery. gene transfer is compared with adenoviral gene transfer control. We characterize the AMD phenotype and changes in the vasculature by using fluorescein angiography, optical coherence tomography, and immunohistochemistry. At early time points, mice exhibit increases in retinal thickness (348 ± 114 µm vs. 231 ± 32 µm) and choroidal neovascularization area (12000 ± 15174 µm² vs. 2169 ± 3495 µm²) compared with the control. At later time points, choroidal neovascularization develops into subretinal fibrovascular membrane. Human VEGF-A expression lasts several weeks. In conclusion, the retinas display vascular abnormalities consistent with choroidal neovascularization. Together with immunohistochemical findings, these changes resemble clinical AMD-like ocular pathologies. We conclude that this mouse model of -induced choroidal neovascularization is useful for mimicking the pathogenesis of AMD, studying the effects of human VEGF-A in the retina, and evaluating anti-VEGF treatments for choroidal neovascularization.
ISSN:2073-4425
2073-4425