Citicoline and lithium rescue retinal ganglion cells following partial optic nerve crush in the rat
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Citicoline and lithium rescue retinal ganglion cells following partial optic nerve crush in the rat. / Schuettauf, Frank; Rejdak, Robert; Thaler, Sebastian; Bolz, Sylvia; Lehaci, Cristiana; Mankowska, Anna; Zarnowski, Tomasz; Junemann, Anselm; Zagorski, Zbigniew; Zrenner, Eberhart; Grieb, Pawel.
in: EXP EYE RES, Jahrgang 83, Nr. 5, 11.2006, S. 1128-34.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Citicoline and lithium rescue retinal ganglion cells following partial optic nerve crush in the rat
AU - Schuettauf, Frank
AU - Rejdak, Robert
AU - Thaler, Sebastian
AU - Bolz, Sylvia
AU - Lehaci, Cristiana
AU - Mankowska, Anna
AU - Zarnowski, Tomasz
AU - Junemann, Anselm
AU - Zagorski, Zbigniew
AU - Zrenner, Eberhart
AU - Grieb, Pawel
PY - 2006/11
Y1 - 2006/11
N2 - Citicoline and lithium (Li(-)) have been shown to support retinal ganglion cell (RGC) survival and axon regeneration in vitro. Optic nerve crush (ONC) is a model of both brain axonal injury and certain aspects of the glaucomatous degeneration of RGC. We have used this model to quantify protection offered to RGC by these drugs and to determine whether their effects are mediated by enhanced expression of the antiapoptotic protein Bcl-2. Adult rats (6-12 per group) were subjected to ONC accompanied by a contralateral sham operation. Animals were treated intraperitoneally with either vehicle, citicoline sodium (1g/kg daily for up to 7 days and 300 mg/kg daily afterwards), lithium chloride (30 mg/kg daily), or both drugs combined. Fluorogold was injected bilaterally into superior colliculi 1, 5 or 19 days after ONC. Labeled cells were counted under a fluorescence microscope 2 days after tracer injection. In a separate set of experiments the effects of treatments on expression of Bcl-2 in retinas were evaluated by immunohistochemistry. In vehicle-treated animals there was a progressive decrease of RGC density after crush. This decrease was attenuated in citicoline-treated animals 1 week and 3 weeks after the crush. In the lithium-treated group protection was even more pronounced. In animals treated with both drugs RGC protection was similar to that achieved by lithium alone. Bcl-2 immunoreactivity was seen predominantly in retinal ganglion cells. Its increase was recorded in the lithium and citicoline group as well as in animals treated with the combination of both drugs. Both citicoline and lithium protect RGC and their axons in vivo against delayed degeneration triggered by the ONC. Retinoprotective action of both drugs may involve an increase in Bcl-2 expression.
AB - Citicoline and lithium (Li(-)) have been shown to support retinal ganglion cell (RGC) survival and axon regeneration in vitro. Optic nerve crush (ONC) is a model of both brain axonal injury and certain aspects of the glaucomatous degeneration of RGC. We have used this model to quantify protection offered to RGC by these drugs and to determine whether their effects are mediated by enhanced expression of the antiapoptotic protein Bcl-2. Adult rats (6-12 per group) were subjected to ONC accompanied by a contralateral sham operation. Animals were treated intraperitoneally with either vehicle, citicoline sodium (1g/kg daily for up to 7 days and 300 mg/kg daily afterwards), lithium chloride (30 mg/kg daily), or both drugs combined. Fluorogold was injected bilaterally into superior colliculi 1, 5 or 19 days after ONC. Labeled cells were counted under a fluorescence microscope 2 days after tracer injection. In a separate set of experiments the effects of treatments on expression of Bcl-2 in retinas were evaluated by immunohistochemistry. In vehicle-treated animals there was a progressive decrease of RGC density after crush. This decrease was attenuated in citicoline-treated animals 1 week and 3 weeks after the crush. In the lithium-treated group protection was even more pronounced. In animals treated with both drugs RGC protection was similar to that achieved by lithium alone. Bcl-2 immunoreactivity was seen predominantly in retinal ganglion cells. Its increase was recorded in the lithium and citicoline group as well as in animals treated with the combination of both drugs. Both citicoline and lithium protect RGC and their axons in vivo against delayed degeneration triggered by the ONC. Retinoprotective action of both drugs may involve an increase in Bcl-2 expression.
KW - Animals
KW - Apoptosis/drug effects
KW - Cell Count
KW - Cytidine Diphosphate Choline/pharmacology
KW - Disease Models, Animal
KW - Female
KW - Immunohistochemistry/methods
KW - Lithium/pharmacology
KW - Microscopy, Fluorescence/methods
KW - Neuroprotective Agents/pharmacology
KW - Optic Nerve Injuries/physiopathology
KW - Pharmaceutical Vehicles
KW - Proto-Oncogene Proteins c-bcl-2/analysis
KW - Rats
KW - Rats, Inbred BN
KW - Retinal Ganglion Cells/chemistry
U2 - 10.1016/j.exer.2006.05.021
DO - 10.1016/j.exer.2006.05.021
M3 - SCORING: Journal article
C2 - 16876158
VL - 83
SP - 1128
EP - 1134
JO - EXP EYE RES
JF - EXP EYE RES
SN - 0014-4835
IS - 5
ER -
