Citicoline and/or lithium rescue retinal ganglion cells following callibrated partial optic nerve crush in the rat

Abstract

Abstract: : Purpose: Citicoline (cytidine–5’–diphosphocholine), a neuroprotectant effective in animal models of CNS ischemia and trauma, has been shown to prevent RGC degeneration in vitro. Lithium, a well–known mood stabilizer, has been found to promote RGC survival and axon regeneration. We evaluated protection offered by citicoline sodium and/or lithium chloride systemic treatment to the retinal ganglion cells (RGC) in a model of callibrated partial optic nerve crush (PONC) in the rat. Methods: Citicoline sodium (1 g/kg/day for 7 days and 300 mg/kg/day for subsequent 2 weeks) and/or lithium chloride (30 mg/kg/day over 3–week period) were given after induction of retinal ganglion cells (RGC) loss in a model of calibrated partial optic nerve crush (PONC) in the rat. RGC retrogradely labeled with Fluorogold were counted; all data are expressed as percent of the RGC count in the respective SHAM–treated group. Results: PONC resulted in the decrease in the number of labelled RGC per square mm of retina to 44.8% after 7 days and to 28.0% after 3 weeks. Citicoline treatment attenuated this decrease to 70.1% and 53.4%. Treatment with lithium chloride was more effective, 77.3% and 76.8% RGC remained intact. Treatment with the combination of the said doses of citicoline and lithium chloride resulted in the labelling of 88.3% and 73.5% of RGC. Conclusion: Our data indicate that: 1. besides acute axotomy, PONC is followed by a delayed neurodegenerative process which further eliminates RGCs and/or disconnects them from superior colliculi; 2. treatment with both citicoline and lithium spares a significant number of RGC connected to superior colliculi; 3. the possibility that these drugs act through different but complementary mechanisms (eg., neuroprotection and axonal regeneration) requires further study. Sopported by MCIF for R.Rejdak QLK2–CT–2002–51562

Keywords: neuroprotection • ganglion cells • trauma