Citicoline and lithium rescue retinal ganglion cells following partial optic nerve crush in the rat.
ABSTRACT 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.
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ABSTRACT: We investigated the effects of an ethanol extract of C. denticulatum (EECD) in a mouse model of glaucoma established by optic nerve crush (ONC), and found that EECD significantly protected against retinal ganglion cell (RGC) death caused by ONC. Furthermore, EECD effectively protected against N-methyl-D-aspartate-induced damage to the rat retinas. In vitro, EECD attenuated RGC-5 death and significantly blunted the up-regulation of apoptotic proteins induced by 1-buthionine-(S,R)-sulfoximine combined with glutamate, reduced reactive oxygen species production by radical species, and inhibited lipid peroxidation. The major EECD components were found to be chicoric acid and 3,5-dicaffeoylquinic acid (3,5-DCQA) that have shown beneficial effects on retinal degeneration both in vitro and in vivo studies. Thus, EECD could be used as a natural neuroprotective component for glaucoma, and chicoric acid and 3,5-DCQA as mark compounds for the development of functional food.Journal of Agricultural and Food Chemistry 01/2014; 62(6). DOI:10.1021/jf4046232 · 3.11 Impact Factor
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ABSTRACT: Neuroprotection of lithium for axotomized retinal ganglion cells (RGCs) is attributed to upregulated intraretinal Bcl-2. As lithium also upregulates brain-derived neurotrophic factor (BDNF) which can rescue axotomized RGCs, it is hypothesized that lithium could protect RGCs through BDNF. This study investigated this hypothesis and a possible relationship between the dose and protection of lithium. All adult experimental rats received daily intraperitoneal injections of lithium chloride (LiCl) at 30, 60 or 85 mg/kg·bw until they were euthanized 2, 7 or 14 days after left intraorbital optic nerve (ON) transection. Our results revealed that RGC densities promoted and declined with increased dose of LiCl and the highest RGC densities were always in the 60 mg/kg·bw LiCl group at both 7 and 14 day points. Similar promotion and decline in the mRNA and protein levels of intraretinal BDNF were also found at the 14 day point, while such BDNF levels increased in the 30 mg/kg·bw LiCl group but peaked in the 60 and 85 mg/kg·bw LiCl groups at the 7 day point. These findings suggested that lithium can delay the death of axotomized RGCs in a dose-dependent manner within a certain period after ON injury and such beneficial effect is interrelated with an upregulated level of intraretinal BDNF.International Journal of Molecular Sciences 08/2014; 15(8):13550-63. DOI:10.3390/ijms150813550 · 2.34 Impact Factor
Article: Neuroprotektive Ansätze[Show abstract] [Hide abstract]
ABSTRACT: Seit der Einführung der vitreoretinalen Chirurgie vor über 40 Jahren gab es zunächst stetig Bestrebungen, toxische Effekte, die z. B. durch Spüllösungen, Endoillumination oder mechanische Manipulation entstehen können, zu reduzieren. In letzter Zeit gibt es auch Versuche, neurodegenerative Prozesse am Auge durch pharmakologische Intervention zu verhindern. Als ein Beispiel eines solchen neuroprotektiven Ansatzes kann die Verwendung von Taurin als Zusatzstoff in Spüllösungen angesehen werden. Der Einsatz von therapeutischen Substanzen im Rahmen der vitreoretinalen Chirurgie bedeutet hinsichtlich der klinischen Zulassung einen erhöhten Aufwand an präklinischer Testung und klinischen Studien. Derzeit werden praktisch keine Neuroprotektiva im Rahmen vitreoretinaler Chirurgie routinemäßig eingesetzt. Experimentelle Studien deuten jedoch auf ein hohes Potenzial verschiedenster neuroprotektiver Substanzen hin. Der nachfolgende Beitrag soll einen Überblick über aktuelle neuroprotektive Ansätze mit potenzieller Anwendbarkeit in der vitreoretinalen Chirurgie geben und deren klinische Eignung kritisch diskutieren.Der Ophthalmologe 10/2013; 110(10). DOI:10.1007/s00347-013-2831-0 · 0.72 Impact Factor