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J. Beutel, K. Januschowski, K. U. Bartz-Schmidt, S. Grisanti, P. Szurman, M. Lüke; The Effects of Pegaptanib Sodium (Macugen®) on Retinal Function in Isolated Perfused Vertebrate Retina. Invest. Ophthalmol. Vis. Sci. 2009;50(13):77.
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© ARVO (1962-2015); The Authors (2016-present)
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.
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.
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.
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.
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