The role of vascular endothelial growth factor (VEGF) in abnormal vascular changes in the adult rat eye.
The aim of this project was to determine if the subretinal delivery of a recombinant adenovirus encoding vascular endothelial growth factor (VEGF) was sufficient to induce changes resembling choroidal neovascularisation (CNV) in a rat model. A recombinant adenovirus was produced encoding vegf164 cDNA (Ad.RSV.VEGF). Transduction of cultured RPE cells confirmed VEGF expression and ensured the absence of Ad.RSV.VEGF-related toxicity. Following subretinal injection into rat eyes, fluorescein angiography indicated that the in vivo delivery of Ad.RSV.VEGF was associated with vascular leakage. Histological analysis demonstrated that changes resembling the early signs of CNV development were also present in the Ad.RSV.VEGF injected eyes. These results suggest that while a transient VEGF expression in the RPE layer is able to induce CNV-related changes, it may be insufficient for the development of a full neovascular membrane. This study demonstrates that virus-mediated gene delivery, in addition to its clinical applications, is a potentially efficient research tool for investigating gene expression-related physiological changes in vitro and in vivo.
Yu
M J
MJ
Department of Pathology, University of Western Australia, Perth, Australia.
Shen
W Y
WY
Lai
M C
MC
Constable
I J
IJ
Papadimitriou
J M
JM
Rakoczy
P E
PE
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002829:Choroid / Q000033:anatomy & histology / Q000098:blood supply*; D020256:Choroidal Neovascularization; D004195:Disease Models, Animal; D016228:Endothelial Growth Factors / Q000235:genetics* / Q000378:metabolism; D005451:Fluorescein Angiography; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D008222:Lymphokines / Q000235:genetics* / Q000378:metabolism; D010857:Pigment Epithelium of Eye / Q000098:blood supply*; D051381:Rats; D011922:Rats, Mutant Strains; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors