Human Vascular Endothelial Growth Factor A165 Expression Induces the Mouse Model of Neovascular Age-Related Macular Degeneration
| Autor: | Kati Kinnunen, Emmi Kokki, Venla Olsson, Seppo Ylä-Herttuala, Tommi Karttunen |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Genetically modified mouse Pathology medicine.medical_specialty lcsh:QH426-470 genetic structures Neovascularization 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Genetics medicine gene transfer age-related macular degeneration subretinal Genetics (clinical) Retina vascular endothelial growth factor medicine.diagnostic_test business.industry animal model Retinal adenovirus Macular degeneration medicine.disease Fluorescein angiography gene therapy eye diseases Vascular endothelial growth factor lcsh:Genetics 030104 developmental biology Choroidal neovascularization medicine.anatomical_structure chemistry 030221 ophthalmology & optometry sense organs neovascularization medicine.symptom business |
| Zdroj: | Genes Volume 9 Issue 9 Genes, Vol 9, Iss 9, p 438 (2018) |
| ISSN: | 2073-4425 |
| DOI: | 10.3390/genes9090438 |
| Popis: | 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 µ m vs. 231 ± 32 µ m) and choroidal neovascularization area (12000 ± 15174 µ m2 vs. 2169 ± 3495 µ m2) 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. |
| Databáze: | OpenAIRE |
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