Abstract
Purpose: :
Nowadays intraocular anti-VEGF therapy is the primary choice in the treatment of neovascular maculopathy. Pegabtanib sodium (Macugen®, Eyetech Pharmaceuticals; Pfizer Inc., New York, New York, USA) inhibits VEGF165 specifically, but is known that all VEGF-A isoforms have also neuroprotective effects avoiding apoptosis of neuronal cells. Therefore, blockage of VEGF165 by pegaptanib sodium could induce retinal dysfunction.
Methods: :
Isolated bovine retinas were perfused with an oxygen preincubated nutrient solution. The electroretinogram (ERG) was recorded as a transretinal potential using Ag/AgCl electrodes. Pegaptanib sodium (0.006 mg/mL, 0.06 mg/mL, 0.2 mg/mL according to an intravitreously injected dose of 0.03 mg, 0.3 mg and 1 mg) or the solvent carrier was added to the nutrient solution for 45 min. Thereafter, the retina was reperfused for 75 min with normal nutrient solution. The percentage of a- and b-wave reduction during the application of pegaptanib sodium or the solvent carrier was calculated.
Results: :
During the application of the two lower concentrations of pegaptanib sodium (0.006 mg/mL, and 0.06 mg/mL) only a slight not-significant reduction of the b-wave amplitude (p = 0.357 and p = 0.31, respectively) and a-wave amplitude (p = 0.189 and p = 0.46, respectively) was observed. At the highest tested concentration of 0.2 mg/mL a slight not significant improvement of the b-wave amplitude (9.2%, p = 0.11) and a-wave amplitude (8.3%, p = 0.23) was detected. The solvent carrier had no effects on the ERG (p = 0.98 and p = 0.42, respectively). During the washout, the ERG-amplitudes of all test series remained unchanged.
Conclusions: :
The present study suggests that pegaptanib sodium with its solvent carrier has a wide safety profile and a good biocompatibility. An intraocular application of 0.3 mg pegaptanib sodium seems to be safe provoking no toxic short-term effects on retinal function.
Keywords: drug toxicity/drug effects • electroretinography: non-clinical • age-related macular degeneration