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Genes 2018, 9(9), 438; https://doi.org/10.3390/genes9090438

Human Vascular Endothelial Growth Factor A165 Expression Induces the Mouse Model of Neovascular Age-Related Macular Degeneration

1
A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70150 Kuopio, Finland
2
Department of Ophthalmology, Kuopio University Hospital, 70210 Kuopio, Finland
3
Department of Ophthalmology, Institute of Clinical Medicine, University of Eastern Finland, 70029 Kuopio, Finland
4
Heart Center and Gene Therapy Unit, Kuopio University Hospital, 70029 Kuopio, Finland
*
Author to whom correspondence should be addressed.
Received: 31 July 2018 / Revised: 24 August 2018 / Accepted: 28 August 2018 / Published: 31 August 2018
(This article belongs to the Special Issue Eye Genetics and Therapies)
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Abstract

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-A165 in the eye. We use a transgenic mouse in which human VEGF-A165 has been silenced with the loxP-STOP fragment. The choroidal neovascularization and human VEGF-A165 expression in the mouse are induced by subretinal adenoviral Cre gene delivery. Cre gene transfer is compared with adenoviral LacZ 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-A165 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 Cre-induced choroidal neovascularization is useful for mimicking the pathogenesis of AMD, studying the effects of human VEGF-A165 in the retina, and evaluating anti-VEGF treatments for choroidal neovascularization. View Full-Text
Keywords: adenovirus; age-related macular degeneration; animal model; gene therapy; gene transfer; neovascularization; subretinal; vascular endothelial growth factor adenovirus; age-related macular degeneration; animal model; gene therapy; gene transfer; neovascularization; subretinal; vascular endothelial growth factor
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Kokki, E.; Karttunen, T.; Olsson, V.; Kinnunen, K.; Ylä-Herttuala, S. Human Vascular Endothelial Growth Factor A165 Expression Induces the Mouse Model of Neovascular Age-Related Macular Degeneration. Genes 2018, 9, 438.

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