title: Transforming growth factor-β inhibition decreases diode laser-induced choroidal neovascularization development in rats: P17 and P144 peptides.
abstract: OBJECTIVE
  To assess the effect of transforming growth factor (TGF)-β inhibitor peptides (P17 and P144) on the development of laser-induced choroidal neovascularization (LI-CNV) in a rat model.
  
  
  METHODS
  Sixty-one Long-Evans rats underwent diode LI-CNV model. Forty-eight hours later, treatment was administered. The intravenous control group (IV-control) and intravenous P17 group (IV-17) received five doses (0.2 mg every 72 hours) of vehicle and P17, respectively. Four groups received intravitreal injections of P17 low-dose (LD-17; 1 mg/mL) and high-dose (HD-17; 20 mg/mL) and P144 low-dose (LD-144; 1 mg/mL) and high-dose (HD-144; 3 mg/mL), and fellow eyes received vehicle. CNV evolution was assessed weekly by fluorescein angiography (FA). After death, VEGF, TGF-β and PDGF protein levels were measured by ELISA in RPE and retina homogenates. Data were analyzed with commercially available statistical analysis software.
  
  
  RESULTS
  The mean CNV area, measured in pixels, was significantly lower at the second and fourth weeks in IV-17 (P < 0.05) and from the second week in HD-17 (P < 0.05), whereas LD-144 and HD-144 showed significant differences at every time point (P < 0.05). LD-17 showed significantly lower protein levels of TGF-β in retina and PDGF in RPE (P < 0.05), whereas HD-17 showed lower levels of VEGF (RPE and retina; P < 0.05), TGF-β (RPE and retina; P < 0.05), and PDGF (RPE; P < 0.05). HD-144 showed lower VEGF levels in the retina (P < 0.05).
  
  
  CONCLUSIONS
  TGF-β inhibition with these peptides represents a promising new therapeutic line for CNV targeting a different pathway than current therapies. More studies are needed to assess this effect on early CNV, alone or in combination with anti-VEGF.
authors.affiliation: Experimental Ophthalmology Laboratory.
authors.forename: Sergio
authors.initials: S
authors.lastname: Recalde
authors.forename: Javier
authors.initials: J
authors.lastname: Zarranz-Ventura
authors.forename: Patricia
authors.initials: P
authors.lastname: Fernández-Robredo
authors.forename: Pío J
authors.initials: PJ
authors.lastname: García-Gómez
authors.forename: Angel
authors.initials: A
authors.lastname: Salinas-Alamán
authors.forename: Francisco
authors.initials: F
authors.lastname: Borrás-Cuesta
authors.forename: Javier
authors.initials: J
authors.lastname: Dotor
authors.forename: Alfredo
authors.initials: A
authors.lastname: García-Layana
mesh_terms: D000818:Animals; D020256:Choroidal Neovascularization / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005451:Fluorescein Angiography; D007275:Injections, Intravenous; D058449:Intravitreal Injections; D017075:Laser Coagulation; D054023:Lasers, Semiconductor; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C562050:P17 peptide; D010446:Peptide Fragments; D010455:Peptides; D010982:Platelet-Derived Growth Factor; D018125:Receptors, Transforming Growth Factor beta; C504795:TGF-beta1 type III receptor (730-743), human; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat