Marked inhibition of retinal neovascularization in rats following soluble-flt-1 gene transfer
Article first published online: 30 MAR 2004
Copyright © 2004 John Wiley & Sons, Ltd.
The Journal of Gene Medicine
Volume 6, Issue 9, pages 992–1002, September 2004
How to Cite
Rota, R., Riccioni, T., Zaccarini, M., Lamartina, S., Gallo, A. D., Fusco, A., Kovesdi, I., Balestrazzi, E., Abeni, D. C., Ali, R. R. and Capogrossi, M. C. (2004), Marked inhibition of retinal neovascularization in rats following soluble-flt-1 gene transfer. J. Gene Med., 6: 992–1002. doi: 10.1002/jgm.586
- Issue published online: 7 SEP 2004
- Article first published online: 30 MAR 2004
- Manuscript Accepted: 29 JAN 2004
- Manuscript Revised: 8 JAN 2004
- Manuscript Received: 11 JUL 2003
- Italian Telethon Foundation. Grant Number: A117
- vascular endothelial growth factor;
- retinal neovascularization;
- gene therapy;
- adenoviral vector
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.
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).
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.
Adenoviral-mediated sflt-1 gene transfer induces a near-complete inhibition of ischemia-induced retinal neovascularization in rats without affecting pre-existing retinal vessels. Copyright © 2004 John Wiley & Sons, Ltd.