title: Fucoidan reduces secretion and expression of vascular endothelial growth factor in the retinal pigment epithelium and reduces angiogenesis in vitro.
abstract: Fucoidan is a polysaccharide isolated from brown algae which is of current interest for anti-tumor therapy. In this study, we investigated the effect of fucoidan on the retinal pigment epithelium (RPE), looking at physiology, vascular endothelial growth factor (VEGF) secretion, and angiogenesis, thus investigating a potential use of fucoidan for the treatment of exudative age-related macular degeneration. For this study, human RPE cell line ARPE-19 and primary porcine RPE cells were used, as well as RPE/choroid perfusion organ cultures. The effect of fucoidan on RPE cells was investigated with methyl thiazolyl tetrazolium--assay, trypan blue exclusion assay, phagocytosis assay and a wound healing assay. VEGF expression was evaluated in immunocytochemistry and Western blot, VEGF secretion was evaluated in ELISA. The effect of fucoidan on angiogenesis was tested in a Matrigel assay using calcein-AM vital staining, evaluated by confocal laser scanning microcopy and quantitative image analysis. Fucoidan displays no toxicity and does not diminish proliferation or phagocytosis, but reduces wound healing in RPE cells. Fucoidan decreases VEGF secretion in RPE/choroid explants and RPE cells. Furthermore, it diminishes VEGF expression in RPE cells even when co-applied with bevacizumab. Furthermore, fucoidan reduces RPE-supernatant- and VEGF-induced angiogenesis of peripheral endothelial cells. In conclusion, fucoidan is a non-toxic agent that reduces VEGF expression and angiogenesis in vitro and may be of interest for further studies as a potential therapy against exudative age-related macular degeneration.
authors.affiliation: University of Kiel, University Medical Center, Department of Ophthalmology, Kiel, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Dithmer
authors.affiliation: University of Kiel, University Medical Center, Experimental Trauma Surgery, Kiel, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Fuchs
authors.affiliation: University of Kiel, University Medical Center, Experimental Trauma Surgery, Kiel, Germany.
authors.forename: Yang
authors.initials: Y
authors.lastname: Shi
authors.affiliation: MetaPhysiol, Essenheim, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Schmidt
authors.affiliation: University of Kiel, University Medical Center, Department of Ophthalmology, Kiel, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Richert
authors.affiliation: University of Kiel, University Medical Center, Department of Ophthalmology, Kiel, Germany.
authors.forename: Johann
authors.initials: J
authors.lastname: Roider
authors.affiliation: University of Kiel, University Medical Center, Department of Ophthalmology, Kiel, Germany.
authors.forename: Alexa
authors.initials: A
authors.lastname: Klettner
mesh_terms: D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D002460:Cell Line; D003094:Collagen; D004338:Drug Combinations; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007150:Immunohistochemistry; D007797:Laminin; D008268:Macular Degeneration / Q000188:drug therapy; D018613:Microscopy, Confocal; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D011134:Polysaccharides / Q000494:pharmacology*; D011509:Proteoglycans; D055213:Retinal Pigment Epithelium / Q000378:metabolism*; D013778:Tetrazolium Salts; D013844:Thiazoles; D014343:Trypan Blue; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D004338:Drug Combinations; D007797:Laminin; D011134:Polysaccharides; D011509:Proteoglycans; D013778:Tetrazolium Salts; D013844:Thiazoles; D042461:Vascular Endothelial Growth Factor A; C059485:matrigel; D000068258:Bevacizumab; D003094:Collagen; C007789:fucoidan; C022616:thiazolyl blue; D014343:Trypan Blue