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.
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.
Authors: Michael I Dorrell; Edith Aguilar; Lea Scheppke; Faith H Barnett; Martin Friedlander Journal: Proc Natl Acad Sci U S A Date: 2007-01-08 Impact factor: 11.205
Authors: F Giansanti; G Virgili; A Bini; E Rapizzi; G Giacomelli; M C Donati; T Verdina; U Menchini Journal: Eur J Ophthalmol Date: 2007 Mar-Apr Impact factor: 2.597
Authors: M Relf; S LeJeune; P A Scott; S Fox; K Smith; R Leek; A Moghaddam; R Whitehouse; R Bicknell; A L Harris Journal: Cancer Res Date: 1997-03-01 Impact factor: 12.701
Authors: Yoshito Takeda; Alexander R Kazarov; Catherine E Butterfield; Benjamin D Hopkins; Laura E Benjamin; Arja Kaipainen; Martin E Hemler Journal: Blood Date: 2006-10-05 Impact factor: 22.113
Authors: Andreas Stahl; Tim U Krohne; Przemyslaw Sapieha; Jing Chen; Ann Hellstrom; Emily Chew; Frank G Holz; Lois E H Smith Journal: Br J Ophthalmol Date: 2011-03-18 Impact factor: 4.638
Authors: Zhenyu Dong; Andrea Santeford; Norimitsu Ban; Tae Jun Lee; Craig Smith; David M Ornitz; Rajendra S Apte Journal: Exp Eye Res Date: 2019-08-23 Impact factor: 3.467
Authors: Anil Kumar; Xu Hou; Chunsik Lee; Yang Li; Arvydas Maminishkis; Zhongshu Tang; Fan Zhang; Harald F Langer; Pachiappan Arjunan; Lijin Dong; Zhijian Wu; Linda Y Zhu; Lianchun Wang; Wang Min; Peter Colosi; Triantafyllos Chavakis; Xuri Li Journal: J Biol Chem Date: 2010-03-15 Impact factor: 5.157
Authors: Judith C Booij; Jacoline B ten Brink; Sigrid M A Swagemakers; Annemieke J M H Verkerk; Anke H W Essing; Peter J van der Spek; Arthur A B Bergen Journal: PLoS One Date: 2010-03-09 Impact factor: 3.240
Authors: Pedro Cuevas; Luis A Outeiriño; Carlos Azanza; Javier Angulo; Guillermo Giménez-Gallego Journal: Eur J Med Res Date: 2012-07-12 Impact factor: 2.175
Authors: Andreas Stahl; Michael T Stumpp; Anja Schlegel; Savira Ekawardhani; Christina Lehrling; Gottfried Martin; Maya Gulotti-Georgieva; Denis Villemagne; Patrik Forrer; Hansjürgen T Agostini; H Kaspar Binz Journal: Angiogenesis Date: 2012-09-15 Impact factor: 9.596