title: Intraocular gutless adenoviral-vectored VEGF stimulates anterior segment but not retinal neovascularization.
abstract: 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.
authors.affiliation: Department of Ophthalmology, The Johns Hopkins University School of Medicine, Maumenee, Baltimore, Maryland 21287, USA.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Oshima
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Takahashi
authors.forename: Sachiko
authors.initials: S
authors.lastname: Oshima
authors.forename: Yoshitsugu
authors.initials: Y
authors.lastname: Saishin
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Saishin
authors.forename: Raquel Lima
authors.initials: RL
authors.lastname: Silva
authors.forename: Xaoling
authors.initials: X
authors.lastname: Liang
authors.forename: P Seshidhar
authors.initials: PS
authors.lastname: Reddy
authors.forename: Shanthi
authors.initials: S
authors.lastname: Ganesh
authors.forename: Terrence
authors.initials: T
authors.lastname: Brann
authors.forename: Gene
authors.initials: G
authors.lastname: Liau
authors.forename: Michael
authors.initials: M
authors.lastname: Kaleko
authors.forename: Sheila
authors.initials: S
authors.lastname: Connelly
authors.forename: Peter A
authors.initials: PA
authors.lastname: Campochiaro
mesh_terms: 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
chemical_list: 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