title: The Role of LOX and LOXL2 in the Pathogenesis of an Experimental Model of Choroidal Neovascularization.
abstract: OBJECTIVE
  We investigated whether lysyl oxidase (LOX) and lysyl oxidase-like 2 (LOXL2) play a role in an experimental model of choroidal neovascularization (CNV). The therapeutic potential of antibodies against LOX (M64) and LOXL2 (AB0023) was evaluated in a murine laser-induced CNV model.
  
  
  METHODS
  Expression of LOX and LOXL2 in the posterior eye cups (including retina, retinal pigment epithelium, choroid, and sclera) was studied by qRT-PCR and immunohistochemistry. In the murine model of CNV, both antibodies were administered intraperitoneally every other day until the day killed. On different time points after laser, treatment outcome was studied by immunohistochemical analysis of inflammation, angiogenesis and fibrosis, and by transcript analysis of different cytokines.
  
  
  RESULTS
  Levels of LOX and LOXL2 in the posterior eye cups were increased after CNV-induction at different time points after laser. At day 35, their protein expression patterns appeared to correlate with retinal glial cells and endothelial cells, respectively. Both antibodies significantly inhibited fibrosis, whereas AB0023 also significantly reduced angiogenesis and inflammation. Transcript levels of α-1 type I collagen (COL1A1) in the posterior eye cups were significantly decreased in lasered mice treated with either M64 or AB0023. Vascular endothelial growth factor expression was also reduced only after AB0023 treatment, whereas activated fibroblast marker α-smooth muscle actin (αSMA) levels were not significantly changed.
  
  
  CONCLUSIONS
  This study suggests that LOX and LOXL2 may play an important role in the pathogenesis of AMD. Targeting LOXL2 could have a broader efficacy than targeting LOX, by reducing angiogenesis and inflammation, as well as fibrosis.
authors.affiliation: KU Leuven - University of Leuven, Department of Neurosciences, Laboratory of Ophthalmology, Leuven, Belgium.
authors.forename: Tine
authors.initials: T
authors.lastname: Van Bergen
authors.affiliation: Gilead Sciences, Foster City, California, United States.
authors.forename: Rhyannon
authors.initials: R
authors.lastname: Spangler
authors.affiliation: Gilead Sciences, Foster City, California, United States.
authors.forename: Derek
authors.initials: D
authors.lastname: Marshall
authors.affiliation: KU Leuven - University of Leuven, Department of Neurosciences, Laboratory of Ophthalmology, Leuven, Belgium.
authors.forename: Karolien
authors.initials: K
authors.lastname: Hollanders
authors.affiliation: KU Leuven - University of Leuven, Department of Neurosciences, Laboratory of Ophthalmology, Leuven, Belgium.
authors.forename: Sara
authors.initials: S
authors.lastname: Van de Veire
authors.affiliation: KU Leuven - University of Leuven, Department of Neurosciences, Laboratory of Ophthalmology, Leuven, Belgium 3University Hospitals Leuven, Department of Ophthalmology, Leuven, Belgium.
authors.forename: Evelien
authors.initials: E
authors.lastname: Vandewalle
authors.affiliation: KU Leuven - University of Leuven, Department of Neurosciences, Laboratory of Ophthalmology, Leuven, Belgium 4KU Leuven - University of Leuven, Department of Biology, Unit Animal Physiology and Neurobiology, Leuven, Belgium.
authors.forename: Lieve
authors.initials: L
authors.lastname: Moons
authors.affiliation: KU Leuven - University of Leuven, Interface Valorization Platform (IVAP), Leuven, Belgium.
authors.forename: Jean
authors.initials: J
authors.lastname: Herman
authors.affiliation: Gilead Sciences, Foster City, California, United States.
authors.forename: Victoria
authors.initials: V
authors.lastname: Smith
authors.affiliation: KU Leuven - University of Leuven, Department of Neurosciences, Laboratory of Ophthalmology, Leuven, Belgium 3University Hospitals Leuven, Department of Ophthalmology, Leuven, Belgium.
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Stalmans
mesh_terms: D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D002829:Choroid / Q000378:metabolism* / Q000473:pathology; D020256:Choroidal Neovascularization / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis / Q000235:genetics*; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D008249:Protein-Lysine 6-Oxidase / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D016326:Extracellular Matrix Proteins; D012333:RNA, Messenger; C077112:Lox protein, mouse; D000594:Amino Acid Oxidoreductases; C485601:Loxl2 protein, mouse; D008249:Protein-Lysine 6-Oxidase