Investigating retinal toxicity of tempol in a model of isolated and perfused bovine retina

Graefes Arch Clin Exp Ophthalmol. 2014 Jun;252(6):935-41. doi: 10.1007/s00417-014-2632-4. Epub 2014 May 2.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cattle
  • Cyclic N-Oxides / toxicity*
  • Electroretinography / drug effects*
  • Models, Animal*
  • Neuroprotective Agents / toxicity*
  • Photic Stimulation
  • Retina / drug effects*
  • Spin Labels

Substances

  • Cyclic N-Oxides
  • Neuroprotective Agents
  • Spin Labels
  • tempol