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

ABSTRACT

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 at termination 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.