Investigating retinal toxicity of tempol in a model of isolated and perfused bovine retina.
OBJECTIVE
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.
Centre for Ophthalmology, University Eye Hospital Tübingen, Schleichstr. 12, 72076, Tübingen, Germany.
Kai
K
Januschowski
Sebastian
S
Mueller
Rebecca
R
Dollinger
Sven
S
Schnichels
Johanna
J
Hofmann
Martin S
MS
Spitzer
Karl-Ulrich
KU
Bartz-Schmidt
Peter
P
Szurman
Sebastian
S
Thaler
D000818:Animals; D002417:Cattle; D003497:Cyclic N-Oxides / Q000633:toxicity*; D004596:Electroretinography / Q000187:drug effects*; D023421:Models, Animal; D018696:Neuroprotective Agents / Q000633:toxicity*; D010775:Photic Stimulation; D012160:Retina / Q000187:drug effects*; D013113:Spin Labels
D003497:Cyclic N-Oxides; D018696:Neuroprotective Agents; D013113:Spin Labels; C001803:tempol