title: The Urokinase Receptor-Derived Peptide UPARANT Mitigates Angiogenesis in a Mouse Model of Laser-Induced Choroidal Neovascularization.
abstract: A mouse model of age-related macular degeneration (AMD) was used to investigate the anti-angiogenic and anti-inflammatory role of UPARANT in laser-induced choroidal neovascularization (CNV).
  
  
  
  Choroidal neovascularization was induced by laser photocoagulation, and UPARANT was intravitreally injected. Some experiments were also performed after either intravitreal injection of anti-VEGF drugs or systemic administration of UPARANT. Immunohistochemistry using CD31 antibodies was used to evaluate the area of CNV. Evans blue dye extravasation was quantitatively assessed. Transcripts of markers of outer blood retinal barrier were measured by quantitative RT-PCR, also used to evaluate angiogenesis and inflammation markers. Western blot was used to determine levels of transcription factors encoding genes involved in angiogenesis and inflammation. Levels of urokinase-type plasminogen activator (uPA), its receptor (uPAR), and formyl peptide receptors (FPRs) were determined at the transcript and the protein level.
  
  
  
  Intravitreal UPARANT reduced the CNV area and the leakage from the choroid. The uPA/uPAR/FPR system was upregulated in CNV, but was not influenced by UPARANT. UPARANT recovered laser-induced upregulation of transcription factors encoding angiogenic and inflammatory markers. Accordingly, angiogenic and inflammatory factors were also reduced. UPARANT as compared to anti-VEGF drugs displayed similar effects on CNV area.
  
  
  
  UPARANT mitigates laser-induced CNV by inhibiting angiogenesis and inflammation through an action on transcription factors encoding angiogenesis and inflammatory genes. The finding that UPARANT is effective against CNV may help to establish uPAR and its membrane partners as putative targets in the treatment of AMD.
authors.affiliation: Department of Biology University of Pisa, Pisa, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Cammalleri
authors.affiliation: Department of Biology University of Pisa, Pisa, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Dal Monte
authors.affiliation: Department of Biology University of Pisa, Pisa, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Locri
authors.affiliation: Department of Chemical Sciences, University of Napoli Federico II, Napoli, Italy.
authors.forename: Liliana
authors.initials: L
authors.lastname: Lista
authors.affiliation: Department of Clinical Neurosciences, Section of Ophthalmology and Vision, St. Erik Hospital, Karolinska Institute, Stockholm, Sweden.
authors.forename: Monica
authors.initials: M
authors.lastname: Aronsson
authors.affiliation: Department of Clinical Neurosciences, Section of Ophthalmology and Vision, St. Erik Hospital, Karolinska Institute, Stockholm, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Kvanta
authors.affiliation: Sooft Italia Spa, Montegiorgio, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Rusciano
authors.affiliation: Department of Experimental Medicine, Second University of Napoli, Napoli, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: De Rosa
authors.affiliation: Department of Chemical Sciences, University of Napoli Federico II, Napoli, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Pavone
authors.affiliation: Department of Clinical Neurosciences, Section of Ophthalmology and Vision, St. Erik Hospital, Karolinska Institute, Stockholm, Sweden.
authors.forename: Helder
authors.initials: H
authors.lastname: André
authors.affiliation: Department of Biology University of Pisa, Pisa, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Bagnoli
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002829:Choroid / Q000473:pathology*; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D058449:Intravitreal Injections; D017075:Laser Coagulation / Q000009:adverse effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000008:administration & dosage*; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D055293:Receptors, Urokinase Plasminogen Activator / Q000096:biosynthesis / Q000235:genetics; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis / Q000235:genetics
chemical_list: D009842:Oligopeptides; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D055293:Receptors, Urokinase Plasminogen Activator; C000594116:acetyl-arginyl-aminoisobutyryl-arginyl-C(alpha)-methylphenylalaninamide; D014568:Urokinase-Type Plasminogen Activator