Abstract
Purpose
Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidinyl-1-oxyl) is a membrane-permeable superoxide dismutase and potentially neuroprotective substance. This study evaluates the retinal tolerance of 0.5 mM, 1 mM, 2 mM, and 5 mM tempol measured by the electroretinogram (ERG) of an isolated and perfused retina whole mount.
Methods
For functionality testing, bovine retinas were prepared and perfused with an oxygen-saturated standard solution, and the ERG was recorded until stable b-wave amplitudes were reached. Tempol concentrations of 0.5 mM, 1 mM, 2 mM, and 5 mM were tested for 45 minutes. To investigate the effects on photoreceptor function, 1 mM aspartate was added to suppress the b-wave and obtain isolated a-waves. ERG amplitudes were monitored for 100 minutes.
Results
While no toxic effects for concentrations of 0.5 mM and 1 mM tempol could be detected, concentrations of 2 mM tempol and higher caused statistically significant negative effects on the b-wave amplitude (−38 %, p = 0.02 for 2 mM; −54 %, p = 0.02 for 5 mM). The a-wave amplitude remained stable even at higher concentrations.
Conclusions
Although the photoreceptors seem to have a tolerance to high concentrations of tempol, higher intravitreal concentrations than 1 mM should be considered critical.
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Acknowledgement
We would like to thank Regina Ebenhoch for her unremitting support. S. Thaler was supported by a grant from the Neuroophthalmologische Gesellschaft, Tuebingen, Germany.
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Kai Januschowski and Sebastian Mueller: these authors contributed equally
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Januschowski, K., Mueller, S., Dollinger, R. et al. Investigating retinal toxicity of tempol in a model of isolated and perfused bovine retina. Graefes Arch Clin Exp Ophthalmol 252, 935–941 (2014). https://doi.org/10.1007/s00417-014-2632-4
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DOI: https://doi.org/10.1007/s00417-014-2632-4