TY - JOUR
T1 - Marked inhibition of retinal neovascularization in rats following soluble-flt-1 gene transfer
AU - Rota, Rossella
AU - Riccioni, Teresa
AU - Zaccarini, Marco
AU - Lamartina, Stefania
AU - Del Gallo, Anna
AU - Fusco, Angelo
AU - Kovesdi, Imre
AU - Balestrazzi, Emilio
AU - Abeni, Damiano C.
AU - Ali, Robin R.
AU - Capogrossi, Maurizio C.
PY - 2004/9
Y1 - 2004/9
N2 - 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 β-galactosidase (Ad.βGal). 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.βGal-treated retinas. Conclusion. Adenoviral-mediated sflt-1 gene transfer induces a near-complete inhibition of ischemia-induced retinal neovascularization in rats without affecting pre-existing retinal vessels.
AB - 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 β-galactosidase (Ad.βGal). 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.βGal-treated retinas. Conclusion. Adenoviral-mediated sflt-1 gene transfer induces a near-complete inhibition of ischemia-induced retinal neovascularization in rats without affecting pre-existing retinal vessels.
KW - Adenoviral vector
KW - Gene therapy
KW - Retinal neovascularization
KW - Vascular endothelial growth factor
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U2 - 10.1002/jgm.586
DO - 10.1002/jgm.586
M3 - Article
C2 - 15352072
AN - SCOPUS:20844432009
VL - 6
SP - 992
EP - 1002
JO - Journal of Gene Medicine
JF - Journal of Gene Medicine
SN - 1099-498X
IS - 9
ER -