Abstract
Purpose: :
A member of the VEGF family is the Placental Growth Factor (PlGF). VEGF itself is the most potent promoter of angiogenesis and its importance for ocular vascularising diseases is well known. The contribution of PlGF to angiogenesis is not equally well understood. The main splice variant is PlGF2 which contains a C-terminal heparin-binding domain. During wound healing the removing of the heparin-binding domain diminished angiogenesis. In an OIR mouse model we analysed the influence of the different PlGF splice variants on the neoangiogenesis in the mouse retina.
Methods: :
Three splice variants of PlGF with (PlGF1, PlGF2) and without (PlGFSt) heparin-binding domain were expressed in vitro and the proteins purified. C57Bl/6J mice_the nursing dam and her pups at postnatal day 7_were exposed to 75% oxygen for 5 days and then transferred back to room air. On P14 100 ng of each protein (and 0.9% NaCl as a control) was injected intravitreally into the eyes of the pups. The avascular area and the area of neovascular tufts were quantified on P17 after isolectin IB4 staining, calibrated to the maximal value in the control group (=100%) and compared.
Results: :
On P17 the calibrated avascular area in control eyes treated with NaCl was 89.6±12.7% (N=18) whereas the calibrated area of neovascular tufts was 64.3±27.8%. Injection of PlGF1 resulted in an avascular area of 98.8±14% (N=5, p=0.177) and a reduced calibrated area of neovascular tufts of 49.3±18.2% (N=5, p=0.273). Injection of PlGF2 resulted in a calibrated avascular area of 106.9±20.9% (N=7, p=0.018) and a reduced calibrated area of neovascular tufts of 44.3±20.4% (N=7, p=0.101). Injection of PlGFSt resulted in a calibrated avascular area of 98.8±11.6% (N=3, p=0.256) and a reduced calibrated area of neovascular tufts of 18.8±13.1% (N=3, p=0.005).
Conclusions: :
An additional amount of PlGF1, PlGF2 or PlGFSt was not able to alter significantly the proangiogenic effect of hypoxia on the developing retina in an OIR mouse model. The main influence of VEGF in this process could not be modified by PlGF splice variants.
Keywords: neovascularization • growth factors/growth factor receptors • hypoxia