Adeno-associated virus-mediated expression of vascular endothelial growth factor peptides inhibits retinal neovascularization in a mouse model of oxygen-induced retinopathy.
Vascular endothelial growth factor (VEGF) has been demonstrated to be a key stimulator of retinal neovascularization (NV), the most common cause of severe and progressive vision loss. In this study, we used a mouse model of oxygen-induced retinopathy (OIR) to explore the potential of gene expression and secretion of short VEGF peptides as a treatment. Peptide-encoding fragments of exons 6 and 7 of the VEGF gene were cloned into a recombinant adeno-associated virus (rAAV) vector. Expression of each peptide in vector-injected eyes was confirmed by reverse transcription-polymerase chain reaction and Western blot analysis. Intravitreal injection of each rAAV vector inhibited retinal NV by 71-83% (p < 0.001) compared with contralateral control eyes in the OIR mouse. Injection and expression of these peptides did not seem to affect the normal appearance of the retina. The results demonstrated that exon 6- and 7-derived VEGF peptides effectively inhibited oxygen-induced retinal NV. Therefore, these VEGF peptides have potential in the treatment of angiogenesis-associated retinal diseases in humans.
Deng
Wen-Tao
WT
Department of Ophthalmology and Powell Gene Therapy Center, University of Florida, College of Medicine, Gainesville, FL 32610, USA. wdeng@ufl.edu
Yan
Zuan
Z
Dinculescu
Astra
A
Pang
Jijing
J
Teusner
Jacqueline T
JT
Cortez
Nenita G
NG
Berns
Kenneth I
KI
Hauswirth
William W
WW
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D017931:DNA Primers; D000229:Dependovirus / Q000235:genetics*; D004195:Disease Models, Animal; D005091:Exons; D015316:Genetic Therapy; D005822:Genetic Vectors; D051379:Mice; D008808:Mice, Inbred CBA; D010100:Oxygen / Q000008:administration & dosage* / Q000009:adverse effects; D012164:Retinal Diseases / Q000188:drug therapy* / Q000209:etiology; D015861:Retinal Neovascularization / Q000517:prevention & control*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism / Q000627:therapeutic use
D017931:DNA Primers; D042461:Vascular Endothelial Growth Factor A; D010100:Oxygen