Inhibition of retinal neovascularization by intraocular viral-mediated delivery of anti-angiogenic agents.
Neovascularization characterizes diabetic retinopathy and choroidal neovascularization associated with age-related macular degeneration, the most common causes of severe visual loss in the developed world. Gene transfer to the eye using adeno-associated viral (AAV) vectors is a promising new treatment for inherited and acquired ocular diseases. We used an AAV vector with rapid onset and high levels of gene expression in the retina to deliver three anti-angiogenic factors (pigment epithelium-derived factor, tissue inhibitor of metalloproteinase-3, and endostatin) to the eyes of mice in a mouse model of retinopathy of prematurity. All three vectors inhibited ischemia-induced neovascularization.
Auricchio
Alberto
A
F. M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Behling
Kathryn C
KC
Maguire
Albert M
AM
O'Connor
Erin M
EM
Bennett
Jean
J
Wilson
James M
JM
Tolentino
Michael J
MJ
D020533:Angiogenesis Inhibitors / Q000235:genetics / Q000494:pharmacology*; D003094:Collagen / Q000235:genetics / Q000494:pharmacology*; D003587:Cytomegalovirus / Q000235:genetics; D000229:Dependovirus / Q000235:genetics; D043169:Endostatins; D004730:Endothelium, Vascular / Q000378:metabolism; D005136:Eye Proteins; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D005822:Genetic Vectors; D006801:Humans; D066298:In Vitro Techniques; D009414:Nerve Growth Factors; D010446:Peptide Fragments / Q000235:genetics / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics; D015861:Retinal Neovascularization / Q000188:drug therapy*; D015843:Serpins / Q000235:genetics; D019717:Tissue Inhibitor of Metalloproteinase-3; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics; D014161:Transduction, Genetic; D000099174:Pigment Epithelium-Derived Factor
D020533:Angiogenesis Inhibitors; D003094:Collagen; D043169:Endostatins; D005136:Eye Proteins; D009414:Nerve Growth Factors; D010446:Peptide Fragments; D011506:Proteins; D015843:Serpins; D019717:Tissue Inhibitor of Metalloproteinase-3; D019714:Tissue Inhibitor of Metalloproteinases; D000099174:Pigment Epithelium-Derived Factor; C088390:TIMP3 protein, human