Abstract
Abstract: :
Purpose: Placental growth factor (PlGF) has been implicated in retinal neovascularization, where it may act in synergy with vascular endothelial growth factor-A (VEGF-A). Using selective neutralisation of PlGF during murine retinal vascular development and in a model of hyperoxia-induced proliferative retinopathy we determined the contribution of this peptide to retinal angiogenic processes. Methods: Groups of neonatal mice (n=8) were given intraperitoneal injections of a PlGF or VEGF-A neutralizing antibody or non-immune IgG (5mg/Kg) every day from post-natal day 1 (P1) to P9. The mice were then perfused with FITC-dextran and the degree of retinal vascular development determined on retinal flat-mounts. The regression of the hyaloid vasculature in the various groups was also quantifed in paraffin-embedded sections. Other groups of P7 mice were exposed to 75% oxygen up to P12 after which they were returned to room air and injected with PlGF, VEGF-A or non-immune IgG antibody every other day until P20. At P20 the retinal vasculature was quantified in flat-mounts. Quantification of retinal vascularisation and neovascular tufts was performed using a computer-based analysis system. Results: In the developing retina, neutralisation of VEGF-A caused a significant attenuation of retinal vascular development (p<0.05) although simultaneously there was accelerated regression of the hyaloid. PlGF neutralization failed to alter retinal vascular development, although it did cause a marked persistence of the hyaloid vasculature (p<0.01). In the oxygen-treated mice, as demonstrated previously, neutralization of VEGF-A led to a significant reduction in pre-retinal neovascularisation (P<0.01) when compared to IgG control groups. However, neutralization of PlGF failed to alter the intensity of the neovascular response. Conclusion: The results suggest that PlGF may not act synergistically with VEGF-A since neutralisation of the individual growth factors produced markedly different effects during retinal angiogenesis and hyaloid regression. Further work is required to fully determine the role of PlGF in retinal angiogenic processes.
Keywords: 566 retinal neovascularization • 614 vascular cells • 564 retinal development