Marked inhibition of retinal neovascularization in rats following soluble-flt-1 gene transfer

作者：Rota R^*; Riccioni T; Zaccarini M; Lamartina S; Del Gallo A; Fusco A; Kovesdi I; Balestrazzi E; Abeni DC; Ali RR; Capogrossi MC

来源：Journal of Gene Medicine, 2004, 6(9): 992-1002.

DOI：10.1002/jgm.586

• vascular endothelial growth factor
• retinal neovascularization
• gene therapy
• adenoviral vector

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.
Conclusion Adenoviral-mediated sflt-1 gene transfer induces a nearcomplete inhibition of ischemia-induced retinal neovascularization in rats without affecting pre-existing retinal vessels.

• 出版日期2004-9