Combinatory inhibition of VEGF and FGF2 is superior to solitary VEGF inhibition in an in vitro model of RPE-induced angiogenesis.
BACKGROUND
Choroidal neovascularisation (CNV) as a feature of exudative age-related macular degeneration (AMD) is partially regulated by retinal pigment epithelium (RPE). In this study, the effect of combinatory anti-angiogenic treatment was evaluated using a novel in vitro assay of RPE-induced angiogenesis.


METHODS
RPE isolated from surgically excised CNV-membranes (CNV-RPE) was used to stimulate sprouting of endothelial cell (EC) spheroids in a 3D collagen matrix. The anti-angiogenic effect of solitary anti-VEGF antibodies (bevacizumab) was compared to a combinatory treatment with anti-VEGF and anti-FGF2 antibodies.


RESULTS
Anti-VEGF treatment inactivated all RPE-derived VEGF but was unable to fully inhibit EC sprouting induced by CNV-RPE. Combined anti-VEGF/anti-FGF treatment inactivated both growth factors and reduced EC sprouting significantly.


CONCLUSIONS
RPE from CNV patients expresses angiogenic growth factors that act in part independently of VEGF. Targeted combinatory therapy can be superior to solitary anti-VEGF therapy. One possible candidate for combinatory therapy is FGF2.
Stahl
Andreas
A
Cell Biology Lab, University Eye Hospital Freiburg, Freiburg, Germany.
Paschek
Lilija
L
Martin
Gottfried
G
Feltgen
Nicolas
N
Hansen
Lutz L
LL
Agostini
Hansjürgen T
HT
D000199:Actins / Q000235:genetics; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D002478:Cells, Cultured; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000473:pathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005136:Eye Proteins / Q000235:genetics; D016222:Fibroblast Growth Factor 2 / Q000037:antagonists & inhibitors*; D015870:Gene Expression; D006801:Humans; D007124:Immunoenzyme Techniques; D053538:Keratin-18 / Q000235:genetics; D009414:Nerve Growth Factors / Q000235:genetics; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000187:drug effects* / Q000473:pathology; D015843:Serpins / Q000235:genetics; D018874:Spheroids, Cellular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*; D000099174:Pigment Epithelium-Derived Factor
D000199:Actins; D020533:Angiogenesis Inhibitors; D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D005136:Eye Proteins; D016222:Fibroblast Growth Factor 2; D053538:Keratin-18; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D015843:Serpins; D042461:Vascular Endothelial Growth Factor A; D000099174:Pigment Epithelium-Derived Factor; C488421:KRT18 protein, human