Citicoline and lithium rescue retinal ganglion cells following partial optic nerve crush in the rat.
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.
Schuettauf
Frank
F
Department of Pathophysiology of Vision and Neuro-Ophthalmology, University Eye Hospital, Röntgenweg 11, 72076 Tübingen, Germany. fschuettauf@uni-tuebingen.de
Rejdak
Robert
R
Thaler
Sebastian
S
Bolz
Sylvia
S
Lehaci
Cristiana
C
Mankowska
Anna
A
Zarnowski
Tomasz
T
Junemann
Anselm
A
Zagorski
Zbigniew
Z
Zrenner
Eberhart
E
Grieb
Pawel
P
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002452:Cell Count; D003566:Cytidine Diphosphate Choline / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D007150:Immunohistochemistry / Q000379:methods; D008094:Lithium / Q000494:pharmacology*; D008856:Microscopy, Fluorescence / Q000379:methods; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020221:Optic Nerve Injuries / Q000503:physiopathology*; D014677:Pharmaceutical Vehicles; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D051381:Rats; D011914:Rats, Inbred BN; D012165:Retinal Ganglion Cells / Q000737:chemistry / Q000187:drug effects*
D018696:Neuroprotective Agents; D014677:Pharmaceutical Vehicles; D019253:Proto-Oncogene Proteins c-bcl-2; D003566:Cytidine Diphosphate Choline; D008094:Lithium