title: Effect of chromogranin A-derived vasostatin-1 on laser-induced choroidal neovascularization in the mouse.
abstract: OBJECTIVE
  To verify the effect of vasostatin-1 (VS-1), an anti-angiogenic fragment of chromogranin A, in the prevention of choroidal neovascularization (CNV) in an established mouse model of laser-induced ocular neovascularization.
  
  
  METHODS
  Bruch's membrane, the innermost layer of the choroid, was broken by laser photocoagulation in C57/Bl6 mice, to induce CNV. Mice were then treated daily for 14 days by intraperitoneal injection of VS-1 or vehicle (6 mice/group). CNV and vascular leakage were measured at three time-points (day 0, 7 and 14) in vivo by spectral domain optical coherence tomography (OCT) and fluorescein angiography (FA). Ex vivo analysis of CNV was also performed at day 14 by confocal microscopy analysis of dextran-perfused choroidal flat-mounts.
  
  
  RESULTS
  In vivo analyses showed that VS-1 significantly reduced CNV at day 14 (p = 0.03) and vascular leakage at day 7 (p = 0.01) and 14 (p = 0.04). Ex vivo confocal microscopy analysis of CNV performed on dextran-perfused choroidal flat-mounts at day 14 confirmed the protective activity of VS-1 (p = 0.01). A significant correlation between the results of in vivo and ex vivo analyses of CNV was also observed (p = 0.001, R(2) = 0.81).
  
  
  CONCLUSIONS
  The results indicate that VS-1 can prevent CNV and vascular leakage in a mouse model of ocular neovascularization, suggesting that this polypeptide might have therapeutic activity in human ocular diseases that are complicated by neovascularization or excessive vascular permeability.
authors.affiliation: Complications of Diabetes Unit, Division of Metabolic and Cardiovascular Sciences, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Maestroni
authors.forename: Anna
authors.initials: A
authors.lastname: Maestroni
authors.forename: Simona
authors.initials: S
authors.lastname: Ceglia
authors.forename: Gemma
authors.initials: G
authors.lastname: Tremolada
authors.forename: Monica
authors.initials: M
authors.lastname: Mancino
authors.forename: Angelina
authors.initials: A
authors.lastname: Sacchi
authors.forename: Rosangela
authors.initials: R
authors.lastname: Lattanzio
authors.forename: Ilaria
authors.initials: I
authors.lastname: Zucchiatti
authors.forename: Angelo
authors.initials: A
authors.lastname: Corti
authors.forename: Francesco
authors.initials: F
authors.lastname: Bandello
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Zerbini
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D016570:Bruch Membrane / Q000601:surgery; D002199:Capillary Permeability; D020256:Choroidal Neovascularization / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D053379:Chromogranin A / Q000494:pharmacology*; D004195:Disease Models, Animal; D005451:Fluorescein Angiography; D007274:Injections, Intraperitoneal; D017075:Laser Coagulation / Q000009:adverse effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D010446:Peptide Fragments / Q000494:pharmacology*; D041623:Tomography, Optical Coherence
chemical_list: D020533:Angiogenesis Inhibitors; D053379:Chromogranin A; D010446:Peptide Fragments; C064110:vasostatin I
keywords: mouse model; ocular neovascularization; ophthalmic coherence tomography; vasostatin-1