title: Sema3f Protects Against Subretinal Neovascularization In Vivo.
abstract: Pathological neovascularization of the outer retina is the hallmark of neovascular age-related macular degeneration (nAMD). Building on our previous observations that semaphorin 3F (Sema3f) is expressed in the outer retina and demonstrates anti-angiogenic potential, we have investigated whether Sema3f can be used to protect against subretinal neovascularization in two mouse models. Both in the very low-density lipid-receptor knockout (Vldlr-/-) model of spontaneous subretinal neovascularization as well as in the mouse model of laser-induced choroidal neovascularization (CNV), we found protective effects of Sema3f against the formation of pathologic neovascularization. In the Vldlr-/-model, AAV-induced overexpression of Sema3f reduced the size of pathologic neovascularization by 56%. In the laser-induced CNV model, intravitreally injected Sema3f reduced pathologic neovascularization by 30%. Combined, these results provide the first evidence from two distinct in vivo models for a use of Sema3f in protecting the outer retina against subretinal neovascularization.
authors.affiliation: Department of Ophthalmology, Harvard Medical School, Boston Children's Hospital, 300 Longwood Ave, Boston, MA 02115, USA.
authors.forename: Ye
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Ophthalmology, Harvard Medical School, Boston Children's Hospital, 300 Longwood Ave, Boston, MA 02115, USA.
authors.forename: Raffael
authors.initials: R
authors.lastname: Liegl
authors.affiliation: Department of Ophthalmology, Harvard Medical School, Boston Children's Hospital, 300 Longwood Ave, Boston, MA 02115, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, Killianstrasse 5, 79106 Freiburg, Germany.
authors.forename: Anima
authors.initials: A
authors.lastname: Bühler
authors.affiliation: Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, Killianstrasse 5, 79106 Freiburg, Germany.
authors.forename: Bertan
authors.initials: B
authors.lastname: Cakir
authors.affiliation: Department of Ophthalmology, Harvard Medical School, Boston Children's Hospital, 300 Longwood Ave, Boston, MA 02115, USA.
authors.forename: Steven S
authors.initials: SS
authors.lastname: Meng
authors.affiliation: Department of Ophthalmology, Harvard Medical School, Boston Children's Hospital, 300 Longwood Ave, Boston, MA 02115, USA.
authors.forename: Samuel B
authors.initials: SB
authors.lastname: Burnim
authors.affiliation: Department of Ophthalmology, Harvard Medical School, Boston Children's Hospital, 300 Longwood Ave, Boston, MA 02115, USA.
authors.forename: Chi-Hsiu
authors.initials: CH
authors.lastname: Liu
authors.affiliation: Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, Killianstrasse 5, 79106 Freiburg, Germany.
authors.forename: Tristan
authors.initials: T
authors.lastname: Reuer
authors.affiliation: Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, Killianstrasse 5, 79106 Freiburg, Germany.
authors.forename: Peipei
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, Killianstrasse 5, 79106 Freiburg, Germany.
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Walz
authors.affiliation: Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, Killianstrasse 5, 79106 Freiburg, Germany.
authors.forename: Franziska
authors.initials: F
authors.lastname: Ludwig
authors.affiliation: Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, Killianstrasse 5, 79106 Freiburg, Germany.
authors.forename: Clemens
authors.initials: C
authors.lastname: Lange
authors.affiliation: Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, Killianstrasse 5, 79106 Freiburg, Germany.
authors.forename: Hansjürgen
authors.initials: H
authors.lastname: Agostini
authors.affiliation: Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, Killianstrasse 5, 79106 Freiburg, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Böhringer
authors.affiliation: Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, Killianstrasse 5, 79106 Freiburg, Germany.
authors.forename: Günther
authors.initials: G
authors.lastname: Schlunck
authors.affiliation: Department of Ophthalmology, Harvard Medical School, Boston Children's Hospital, 300 Longwood Ave, Boston, MA 02115, USA.
authors.forename: Lois E H
authors.initials: LEH
authors.lastname: Smith
authors.affiliation: Eye Center, Medical Center, Faculty of Medicine, University of Freiburg, Killianstrasse 5, 79106 Freiburg, Germany. Electronic address: andreas.stahl@uniklinik-freiburg.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Stahl
mesh_terms: D000818:Animals; D020256:Choroidal Neovascularization / Q000209:etiology / Q000473:pathology; D004195:Disease Models, Animal; D005451:Fluorescein Angiography; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D007834:Lasers; D008268:Macular Degeneration / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics; D012160:Retina / Q000378:metabolism / Q000473:pathology; D015861:Retinal Neovascularization / Q000473:pathology / Q000517:prevention & control*
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011973:Receptors, LDL; C491229:Sema3f protein, mouse; C036053:VLDL receptor
keywords: AMD; CNV; Laser-CNV; Neovascularization; RAP; Retina; Sema3f; Semaphorin; VLDLR