Nonhuman primate models for diabetic ocular neovascularization using AAV2-mediated overexpression of vascular endothelial growth factor.
Neovascularization leads to blindness in numerous ocular diseases, including diabetic retinopathy, age-related macular degeneration, retinopathy of prematurity, and sickle cell disease. More effective and stable treatments for ocular neovascularization are needed, yet there are major limitations in the present animal models. To develop primate models of diabetic retinopathy and choroidal neovascularization, rhesus monkeys were injected subretinally or intravitreally with an adeno-associated virus (AAV)-2 vector carrying the cDNA encoding human vascular endothelial growth factor (VEGF). Overexpression of VEGF was measured by intraocular fluid sampling over time. Neovascularization was evaluated by ophthalmoscopy through angiography, optical coherence tomography, and ultimately histopathology. Overexpression of VEGF through AAV2 results in rapid development of features of diabetic retinopathy or macular edema, depending on the targeted cell type/mode of production of VEGF and diffusion of VEGF. Nonhuman primate models will be useful in testing long-term safety and efficacy of novel therapeutic agents for blinding neovascular diseases.
Lebherz
Corinna
C
Department of Medical Genetics, University of Pennsylvania, Philadelphia, Pennsylvania 190104-6069, USA.
Maguire
Albert M
AM
Auricchio
Alberto
A
Tang
Waixing
W
Aleman
Tomas S
TS
Wei
Zhangyong
Z
Grant
Rebecca
R
Cideciyan
Artur V
AV
Jacobson
Samuel G
SG
Wilson
James M
JM
Bennett
Jean
J
D000256:Adenoviridae; D000818:Animals; D000229:Dependovirus; D003930:Diabetic Retinopathy / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression / Q000502:physiology*; D008253:Macaca mulatta; D012160:Retina / Q000648:ultrastructure; D015861:Retinal Neovascularization / Q000503:physiopathology*; D013997:Time Factors; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000502:physiology*; D014780:Viruses
D042461:Vascular Endothelial Growth Factor A