Marked inhibition of retinal neovascularization in rats following soluble-flt-1 gene transfer.
BACKGROUND
In mouse models of retinopathy of prematurity (ROP) inhibitors of vascular endothelial growth factor (VEGF) functions administered systemically completely block retinal neovascularization. In contrast, selective ocular VEGF depletion has achieved an approx. 50% inhibition of retinal neovascular growth. It is unclear whether a more complete inhibition of new blood vessel development can be obtained with an anti-VEGF therapy localized to the eye. Therefore, the objective of the present study was to determine the effect of local anti-VEGF therapy in a different animal model which closely mimics human ROP.


METHODS
Rats were exposed to alternating cycles of high and low levels of oxygen for 14 days immediately after birth; thereafter, they were intravitreally injected with an adenoviral vector expressing a secreted form of the VEGF receptor flt-1 (Ad.sflt), which acts by sequestering VEGF. Contralateral eyes were injected with the control vector carrying the reporter gene expressing beta-galactosidase (Ad.betaGal).


RESULTS
At the peak of retinal neovascular growth, i.e. post-natal day 21 (P21), we observed up to 97.5% decrease in retinal neovascularization in animals injected with Ad.sflt. At the end of observation (P28), no significant difference in retinal vessel number was detected in both oxygen-injured and normoxic Ad.sflt-treated retinas compared with untreated or Ad.betaGal-treated retinas.


CONCLUSIONS
Adenoviral-mediated sflt-1 gene transfer induces a near-complete inhibition of ischemia-induced retinal neovascularization in rats without affecting pre-existing retinal vessels.
Rota
Rossella
R
Laboratory of Cell Biology, Children's Hospital 'Bambino Gesù', I.R.C.C.S., 00165 Rome, Italy. rota@opbg.net
Riccioni
Teresa
T
Zaccarini
Marco
M
Lamartina
Stefania
S
Gallo
Anna Del
AD
Fusco
Angelo
A
Kovesdi
Imre
I
Balestrazzi
Emilio
E
Abeni
Damiano C
DC
Ali
Robin R
RR
Capogrossi
Maurizio C
MC
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000627:therapeutic use; D006801:Humans; D007231:Infant, Newborn; D051381:Rats; D012160:Retina / Q000473:pathology; D015861:Retinal Neovascularization / Q000517:prevention & control*; D012178:Retinopathy of Prematurity / Q000628:therapy*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000096:biosynthesis / Q000235:genetics* / Q000627:therapeutic use*; D014822:Vitreous Body / Q000378:metabolism
D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1