Experimental subretinal neovascularization is inhibited by adenovirus-mediated soluble VEGF/flt-1 receptor gene transfection: a role of VEGF and possible treatment for SRN in age-related macular degeneration.
Accumulating evidence has shown the importance of vascular endothelial growth factor (VEGF) in chorioretinal angiogenesis. However, whether or not VEGF is indeed critical for the pathogenesis of subretinal neovascularization (SRN) in adulthood, which is a serious complication of age-related macular degeneration, has to be further investigated. We constructed an adenovirus expressing an entire ectodomain of the human VEGF receptor/flt-1 fused to Fc portion of human IgG (Adflt-ExR): this soluble receptor is secreted from Adflt-ExR-transfected cells. We studied the effect of Adflt-ExR on the formation of experimental SRN. Experimental SRN was induced by intense photocoagulation on the retina in pigmented rats and Adflt-ExR was injected into the femoral muscle. The formation of SRN assessed by fluorescein angiography was more significantly inhibited for 7 days in the Adflt-ExR-treated rats than in the control rats who received either an adenovirus vector encoding LacZ gene or balanced salt solution (BSS). The serum concentration of this soluble receptor increased for 7 days and thereafter gradually decreased. An immunohistochemical study disclosed the fibroblast cell proliferation and inflammatory cell infiltration to be reduced in the photocoagulation spot of Adflt-ExR-treated rats. VEGF plays a crucial role in the formation of SRN and VEGF soluble receptor gene transfection can inhibit SRN. This method will contribute to future gene therapy for age-related macular degeneration.
Honda
M
M
Department of Ophthalmology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Sakamoto
T
T
Ishibashi
T
T
Inomata
H
H
Ueno
H
H
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D016228:Endothelial Growth Factors / Q000032:analysis / Q000378:metabolism*; D005451:Fluorescein Angiography; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage; D006801:Humans; D007150:Immunohistochemistry; D008222:Lymphokines / Q000032:analysis / Q000378:metabolism*; D008268:Macular Degeneration / Q000378:metabolism / Q000628:therapy*; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics*; D051381:Rats; D011919:Rats, Inbred Strains; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis / Q000235:genetics*; D015861:Retinal Neovascularization / Q000378:metabolism / Q000628:therapy*; D014162:Transfection / Q000379:methods*; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D011518:Proto-Oncogene Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; D040281:Vascular Endothelial Growth Factor Receptor-1