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Int. J. Mol. Sci. 2014, 15(4), 6286-6297; doi:10.3390/ijms15046286
Article

Neuroprotective Effects of Citicoline in in Vitro Models of Retinal Neurodegeneration

1
,
2
,
1
,
1
,
2
,
1
 and
1,*
1 Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Viale Regina Elena, 299, Rome 00161, Italy 2 GB Bietti Eye Foundation IRCCS, Via Livenza, 3, Rome 00198, Italy
* Author to whom correspondence should be addressed.
Received: 12 February 2014 / Revised: 11 March 2014 / Accepted: 25 March 2014 / Published: 14 April 2014
(This article belongs to the Special Issue Neuroprotective Strategies 2014)
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Abstract

In recent years, citicoline has been the object of remarkable interest as a possible neuroprotectant. The aim of this study was to investigate if citicoline affected cell survival in primary retinal cultures and if it exerted neuroprotective activity in conditions modeling retinal neurodegeneration. Primary retinal cultures, obtained from rat embryos, were first treated with increasing concentrations of citicoline (up to 1000 µM) and analyzed in terms of apoptosis and caspase activation and characterized by immunocytochemistry to identify neuronal and glial cells. Subsequently, excitotoxic concentration of glutamate or High Glucose-containing cell culture medium (HG) was administered as well-known conditions modeling neurodegeneration. Glutamate or HG treatments were performed in the presence or not of citicoline. Neuronal degeneration was evaluated in terms of apoptosis and loss of synapses. The results showed that citicoline did not cause any damage to the retinal neuroglial population up to 1000 µM. At the concentration of 100 µM, it was able to counteract neuronal cell damage both in glutamate- and HG-treated retinal cultures by decreasing proapoptotic effects and contrasting synapse loss. These data confirm that citicoline can efficiently exert a neuroprotective activity. In addition, the results suggest that primary retinal cultures, under conditions inducing neurodegeneration, may represent a useful system to investigate citicoline neuroprotective mechanisms.
Keywords: citicoline; glaucoma; excitotoxicity; apoptosis; diabetic retinopathy; primary retinal cultures; neuroprotection citicoline; glaucoma; excitotoxicity; apoptosis; diabetic retinopathy; primary retinal cultures; neuroprotection
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Matteucci, A.; Varano, M.; Gaddini, L.; Mallozzi, C.; Villa, M.; Pricci, F.; Malchiodi-Albedi, F. Neuroprotective Effects of Citicoline in in Vitro Models of Retinal Neurodegeneration. Int. J. Mol. Sci. 2014, 15, 6286-6297.

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