Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Actins / genetics
-
Angiogenesis Inhibitors / pharmacology*
-
Antibodies, Blocking
-
Antibodies, Monoclonal / pharmacology*
-
Antibodies, Monoclonal, Humanized
-
Bevacizumab
-
Cells, Cultured
-
Choroidal Neovascularization / drug therapy*
-
Choroidal Neovascularization / pathology
-
Endothelium, Vascular / drug effects
-
Endothelium, Vascular / metabolism
-
Endothelium, Vascular / pathology
-
Enzyme-Linked Immunosorbent Assay
-
Eye Proteins / genetics
-
Fibroblast Growth Factor 2 / antagonists & inhibitors*
-
Gene Expression
-
Humans
-
Immunoenzyme Techniques
-
Keratin-18 / genetics
-
Nerve Growth Factors / genetics
-
Polymerase Chain Reaction
-
RNA, Messenger / metabolism
-
Retinal Pigment Epithelium / drug effects*
-
Retinal Pigment Epithelium / pathology
-
Serpins / genetics
-
Spheroids, Cellular / drug effects
-
Spheroids, Cellular / metabolism
-
Spheroids, Cellular / pathology
-
Vascular Endothelial Growth Factor A / antagonists & inhibitors*
Substances
-
Actins
-
Angiogenesis Inhibitors
-
Antibodies, Blocking
-
Antibodies, Monoclonal
-
Antibodies, Monoclonal, Humanized
-
Eye Proteins
-
KRT18 protein, human
-
Keratin-18
-
Nerve Growth Factors
-
RNA, Messenger
-
Serpins
-
Vascular Endothelial Growth Factor A
-
pigment epithelium-derived factor
-
Fibroblast Growth Factor 2
-
Bevacizumab