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Diabetes 54:1141-1149, 2005
© 2005 by the American Diabetes Association, Inc.

Nonhuman Primate Models for Diabetic Ocular Neovascularization Using AAV2-Mediated Overexpression of Vascular Endothelial Growth Factor

Corinna Lebherz1, Albert M. Maguire2, Alberto Auricchio3, Waixing Tang2, Tomas S. Aleman2, Zhangyong Wei2, Rebecca Grant1, Artur V. Cideciyan2, Samuel G. Jacobson2, James M. Wilson1, and Jean Bennett2

1 Department of Medical Genetics, University of Pennsylvania, Philadelphia, Pennsylvania
2 Department of Ophthalmology, F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania
3 Telethon Institute of Genetics and Medicine, Naples, Italy

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.

Address correspondence and reprint requests to Jean Bennett MD, PhD, University of Pennsylvania, 310 Stellar Chance Building, 422 Curie Blvd., Philadelphia, PA 190104-6069. E-mail: jebennet{at}mail.med.upenn.edu


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Copyright © 2005 by the American Diabetes Association.