Intraocular gutless adenoviral-vectored VEGF stimulates anterior segment but not retinal neovascularization.
Vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1) have been implicated as important stimulatory factors for retinal neovascularization. In this study, we used intraocular gene transfer with gutless adenoviral (AGV) vectors to determine the effect of increased intraocular expression of VEGF, IGF-1, or sphingosine kinase (SPK), which produces sphingosine-1-phosphate, another angiogenic factor. Retinal neovascularization did not occur from intravitreous AGV-vectored VEGF, IGF-1, SPK, or combined VEGF and IGF-1, except occasionally adjacent to the retinal penetration site from the injection. However, corneal and iris neovascularization occurred after 2 weeks in all eyes injected with AGV.VEGF, but not those injected with only AGV.IGF-1 or AGV.SPK. These data suggest that the superficial capillary bed of the retina is relatively insensitive to VEGF, IGF-1, or SPK in adult mice, except when combined with retinal trauma. However, AGV-vectored VEGF is sufficient to consistently cause severe corneal and iris neovascularization. This provides a model for anterior segment neovascularization, which unlike previous models is relatively inexpensive and is not plagued by spontaneous regression, and therefore, may be useful for identification of new treatments.
Oshima
Yuji
Y
Department of Ophthalmology, The Johns Hopkins University School of Medicine, Maumenee, Baltimore, Maryland 21287, USA.
Takahashi
Kyoichi
K
Oshima
Sachiko
S
Saishin
Yoshitsugu
Y
Saishin
Yumiko
Y
Silva
Raquel Lima
RL
Liang
Xaoling
X
Reddy
P Seshidhar
PS
Ganesh
Shanthi
S
Brann
Terrence
T
Liau
Gene
G
Kaleko
Michael
M
Connelly
Sheila
S
Campochiaro
Peter A
PA
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017931:DNA Primers; D005123:Eye / Q000098:blood supply*; D005822:Genetic Vectors; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000235:genetics; D007763:Lac Operon; D008246:Lysophospholipids / Q000378:metabolism; D051379:Mice; D018919:Neovascularization, Physiologic / Q000235:genetics; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000096:biosynthesis / Q000235:genetics; D015861:Retinal Neovascularization; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism; D014161:Transduction, Genetic; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics; D000099157:Sphingosine Kinase
D017931:DNA Primers; D007334:Insulin-Like Growth Factor I; D008246:Lysophospholipids; D017853:Phosphotransferases (Alcohol Group Acceptor); D013110:Sphingosine; D042461:Vascular Endothelial Growth Factor A; D000099157:Sphingosine Kinase; C060506:sphingosine 1-phosphate