title: Effects of pegaptanib sodium on retinal function in isolated perfused vertebrate retina.
abstract: OBJECTIVE
  To evaluate the short-term toxic effects of pegaptanib sodium on retinal function. At present, intraocular anti-vascular endothelial growth factor (VEGF) therapy is the primary choice of treatment for neovascular maculopathy. The isoform VEGF(165) is specifically inhibited by pegaptanib sodium. Therefore, since VEGF(165) has neuroprotective effects against apoptosis of neuronal cells, blockage of VEGF(165) by pegaptanib could induce retinal dysfunction. In the present study, we used an electrophysiological technique for testing retinal toxicity in order to evaluate the short-term toxic effects of pegaptanib sodium on retinal function in a model of isolated perfused vertebrate retina.
  
  
  METHODS
  Isolated bovine retinas were perfused with an oxygenated, pre-incubated nutrient solution. Electroretinograms (ERGs) were recorded as trans-retinal potentials using Ag/AgCl electrodes. Pegaptanib sodium (0.006, 0.06, or 0.2 mg/ml) and solvent carrier were added to the nutrient solution for 45 min. ERGs were monitored before, during, and after exposure.
  
  
  RESULTS
  No significant reductions of b-wave (p = 0.357, p = 0.31, and p = 0.11, respectively) or a-wave (p = 0.189, p = 0.46, and p = 0.23, respectively) amplitudes were detected during application of pegaptanib (0.006, 0.06, or 0.2 mg/ml). The solvent carrier alone had no effect on ERG b- or a-waves (p = 0.98 and p = 0.42, respectively). During washout, ERG amplitudes of all test series remained unchanged.
  
  
  CONCLUSIONS
  Results suggest that both pegaptanib sodium and its solvent carrier have good safety profiles. Intraocular application of 0.3 mg pegaptanib sodium induced no significant changes in ERGs in our ex vivo model and, thus, appears to be safe.
authors.affiliation: University Eye Hospital, University of Lübeck, Lübeck, Germany. matthias.lueke@uk-sh.de
authors.forename: Matthias
authors.initials: M
authors.lastname: Lüke
authors.forename: Kai
authors.initials: K
authors.lastname: Januschowski
authors.forename: Aysegül
authors.initials: A
authors.lastname: Tura
authors.forename: Julia
authors.initials: J
authors.lastname: Lüke
authors.forename: Khaled
authors.initials: K
authors.lastname: Nassar
authors.forename: Christoph
authors.initials: C
authors.lastname: Lüke
authors.forename: Toni
authors.initials: T
authors.lastname: Schneider
authors.forename: Peter
authors.initials: P
authors.lastname: Szurman
authors.forename: Salvatore
authors.initials: S
authors.lastname: Grisanti
authors.forename: Karl Ulrich
authors.initials: KU
authors.lastname: Bartz-Schmidt
mesh_terms: D020533:Angiogenesis Inhibitors / Q000633:toxicity*; D000818:Animals; D052157:Aptamers, Nucleotide / Q000633:toxicity*; D002417:Cattle; D004596:Electroretinography / Q000187:drug effects; D012160:Retina / Q000187:drug effects* / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
chemical_list: D020533:Angiogenesis Inhibitors; D052157:Aptamers, Nucleotide; D042461:Vascular Endothelial Growth Factor A; C495058:pegaptanib