Effects of Pegaptanib Sodium on Retinal Function in Isolated Perfused Vertebrate Retina

Abstract

Purpose: 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 VEGF₁₆₅ is specifically inhibited by pegaptanib sodium. Therefore, since VEGF₁₆₅ has neuroprotective effects against apoptosis of neuronal cells, blockage of VEGF₁₆₅ 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.

Conclusion: 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.

KEYWORDS::

• Electroretinogram
• Exudative age-related macular degeneration
• Isolated perfused retina
• Macugen
• Pegaptanib sodium
• Retinal biocompatibility

ACKNOWLEDGMENT

This research was supported by an independent grant from Pfizer Pharma GmbH, Berlin, Germany.

Declaration of interest: The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.