Neuroprotective effects of tempol on retinal ganglion cells in a partial optic nerve crush rat model with and without iron load
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Neuroprotective effects of tempol on retinal ganglion cells in a partial optic nerve crush rat model with and without iron load. / Thaler, Sebastian; Fiedorowicz, Michal; Rejdak, Robert; Choragiewicz, Tomasz J; Sulejczak, Dorota; Stopa, Piotr; Zarnowski, Tomasz; Zrenner, Eberhart; Grieb, Pawel; Schuettauf, Frank.
In: EXP EYE RES, Vol. 90, No. 2, 02.2010, p. 254-60.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Neuroprotective effects of tempol on retinal ganglion cells in a partial optic nerve crush rat model with and without iron load
AU - Thaler, Sebastian
AU - Fiedorowicz, Michal
AU - Rejdak, Robert
AU - Choragiewicz, Tomasz J
AU - Sulejczak, Dorota
AU - Stopa, Piotr
AU - Zarnowski, Tomasz
AU - Zrenner, Eberhart
AU - Grieb, Pawel
AU - Schuettauf, Frank
N1 - Copyright 2009 Elsevier Ltd. All rights reserved.
PY - 2010/2
Y1 - 2010/2
N2 - Iron overload can contribute to oxidative stress in many tissues. We studied the effects of pretreatment with iron dextran on RGC loss in a calibrated partial optic nerve crush (PONC) model in rats, along with the protection offered by tempol (4-hydroxy-2,2,6,6-tetramethylpiperidinyl-1-oxyl, a membrane-permeable superoxide dismutase mimetic and free-radical scavenger), in the same experimental paradigm. A total of 40 rats in 6 groups of 5-8 animals each underwent PONC in one eye and sham crush in the other. Animals were pretreated with a single iron dextran load 24 h prior to PONC, and treated with tempol 6 h before and then once daily after PONC. Control animals were treated with PBS. RGC were retrogradely labeled with a fluorescent marker; all data are expressed in percent of the RGC count in the respective sham-treated eye. Immunohistochemistry was performed to visualize 3-nitrotyrosine, a marker of nitroxidative stress. PONC without iron pretreatment resulted in the survival of only 31.4% of labeled RGC after 7 days. Even fewer RGC (12.7%) survived after PONC with iron pretreatment. However, tempol in doses of 20 mg/kg of body weight (BW) significantly attenuated this effect when given as described above; in the group without iron pretreatment the number of surviving RGC doubled from 31.4% to 62.1%. In the group with iron pretreatment the survival rate of RGC increased even more pronouncedly, from 12.7% without tempol to 46.2% with tempol. Tempol in doses of 1 mg/kg BW and 5 mg/kg BW showed no significant rescue of RGC. Immunostaining showed nitrotyrosine-positive RGCs in PONC but not in sham-treated eyes and an increase in positive cells after iron load. Tempol treatment reduced nitrotyrosine staining in both the iron and non-iron groups. Our results demonstrate that PONC results in significantly greater RGC damage when iron pretreatment is performed, and that the compound tempol may provide additional protection for RGC in cases of neuronal damage both with and without prior iron treatment.
AB - Iron overload can contribute to oxidative stress in many tissues. We studied the effects of pretreatment with iron dextran on RGC loss in a calibrated partial optic nerve crush (PONC) model in rats, along with the protection offered by tempol (4-hydroxy-2,2,6,6-tetramethylpiperidinyl-1-oxyl, a membrane-permeable superoxide dismutase mimetic and free-radical scavenger), in the same experimental paradigm. A total of 40 rats in 6 groups of 5-8 animals each underwent PONC in one eye and sham crush in the other. Animals were pretreated with a single iron dextran load 24 h prior to PONC, and treated with tempol 6 h before and then once daily after PONC. Control animals were treated with PBS. RGC were retrogradely labeled with a fluorescent marker; all data are expressed in percent of the RGC count in the respective sham-treated eye. Immunohistochemistry was performed to visualize 3-nitrotyrosine, a marker of nitroxidative stress. PONC without iron pretreatment resulted in the survival of only 31.4% of labeled RGC after 7 days. Even fewer RGC (12.7%) survived after PONC with iron pretreatment. However, tempol in doses of 20 mg/kg of body weight (BW) significantly attenuated this effect when given as described above; in the group without iron pretreatment the number of surviving RGC doubled from 31.4% to 62.1%. In the group with iron pretreatment the survival rate of RGC increased even more pronouncedly, from 12.7% without tempol to 46.2% with tempol. Tempol in doses of 1 mg/kg BW and 5 mg/kg BW showed no significant rescue of RGC. Immunostaining showed nitrotyrosine-positive RGCs in PONC but not in sham-treated eyes and an increase in positive cells after iron load. Tempol treatment reduced nitrotyrosine staining in both the iron and non-iron groups. Our results demonstrate that PONC results in significantly greater RGC damage when iron pretreatment is performed, and that the compound tempol may provide additional protection for RGC in cases of neuronal damage both with and without prior iron treatment.
KW - Animals
KW - Antioxidants/administration & dosage
KW - Cell Count
KW - Cell Survival
KW - Cyclic N-Oxides/administration & dosage
KW - Disease Models, Animal
KW - Dose-Response Relationship, Drug
KW - Hematinics/therapeutic use
KW - Immunoenzyme Techniques
KW - Iron Overload/metabolism
KW - Iron-Dextran Complex/therapeutic use
KW - Neuroprotective Agents/administration & dosage
KW - Optic Nerve Injuries/complications
KW - Oxidative Stress
KW - Rats
KW - Rats, Inbred BN
KW - Retinal Degeneration/etiology
KW - Retinal Ganglion Cells/drug effects
KW - Spin Labels
KW - Tyrosine/analogs & derivatives
U2 - 10.1016/j.exer.2009.10.013
DO - 10.1016/j.exer.2009.10.013
M3 - SCORING: Journal article
C2 - 19883642
VL - 90
SP - 254
EP - 260
JO - EXP EYE RES
JF - EXP EYE RES
SN - 0014-4835
IS - 2
ER -