Strain‐dependent anterior segment neovascularization following intravitreal gene transfer of basic fibroblast growth factor (bFGF)

AR Gupta, NS Dejneka, RJ D'Amato… - The journal of gene …, 2001 - Wiley Online Library
AR Gupta, NS Dejneka, RJ D'Amato, Z Yang, N Syed, AM Maguire, J Bennett
The journal of gene medicine, 2001Wiley Online Library
Background A promising strategy for delaying death of photoreceptor cells in retinal
degenerative disease is to support survival of these cells through intraocular delivery of
growth/neurotrophic factors. One factor that has received great attention is basic fibroblast
growth factor (bFGF; fgf‐2), a known stimulator of angiogenesis. We evaluated the potential
for neovascularization induced by adenovirus‐mediated intravitreal delivery of bFGF.
Methods Recombinant adenoviruses carrying the low molecular weight (18 kD) or the high …
Background
A promising strategy for delaying death of photoreceptor cells in retinal degenerative disease is to support survival of these cells through intraocular delivery of growth/neurotrophic factors. One factor that has received great attention is basic fibroblast growth factor (bFGF; fgf‐2), a known stimulator of angiogenesis. We evaluated the potential for neovascularization induced by adenovirus‐mediated intravitreal delivery of bFGF.
Methods
Recombinant adenoviruses carrying the low molecular weight (18 kD) or the high molecular weight (22, 23 and 24 kD) forms of human bFGF, driven by the cytomegalovirus (CMV) promoter/enhancer, were prepared. Viruses were delivered to eyes of different strains of mice and rats through intravitreal injection. Contralateral eyes were injected with control virus carrying a reporter gene [green fluorescent protein (GFP) or lacZ]. Transgene expression was assessed by Western analysis and by immunohistochemistry. Neovascularization was evaluated in vivo and histologically attermination of the experiment.
Results
Adenovirus‐mediated delivery of the 18 kD form of bFGF resulted in anterior segment neovascularization in a strain‐dependent fashion. Generation of new blood vessels was not observed after injection of the higher molecular weight forms of bFGF or of control solutions.
Conclusion
The low molecular weight form (18 kD) (but not the high molecular weight forms) of bFGF drives angiogenic response in the anterior segment of specific strains of mice. Genetic modifiers may contribute to and/or prevent neovascularization induced by bFGF. Copyright © 2001 John Wiley & Sons, Ltd.
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