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Editors Selection IGR 9-3

Medical treatment: Citicolin

Comment by Martin Wax on:

15272 Citicoline and lithium rescue retinal ganglion cells following partial optic nerve crush in the rat, Schuettauf F; Rejdak R; Thaler S et al., Experimental Eye Research, 2006; 83: 1128-1134

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Few topics elicit more excitement in the glaucoma community than neuroprotection. To be clear, this generally refers to protection or rescue of neuronal function that is either achieved in the absence or presence of intraocular pressure lowering. The latter, of course, is the mainstay of glaucoma therapy, and thus a well accepted mechanism of achieving genuine neuroprotection. However, pressure lowering drugs do not necessarily hold the promise, and hence the excitement, of drugs that may work to protect retinal neurons from cell death in the absence of IOP lowering. Thus the elusive search for pressure independent neuroprotectants continues, despite the plethora of failures in the literature to identify such a compounds as proven in human studies. In the paper by Schuettauf et al. (1014), the neuroprotectant efficacy of citicoline and lithium was assessed in rats that were subjected to optic nerve crush injury. Citicoline is cytidine-50 diphosphocholine (CDP-choline), a compound that has been in clinical use for many years in Europe and Japan for a variety of degenerative neurological disorders. It is an intermediate in the biosynthesis of phosphotidylcholine, which is of key importance in regulating cell membrane integrity. Studies on the effects of citicoline on ischemic damage in experimental animals go back several years and there is good evidence for its efficacy in several animal models of acute ischemic stroke although its efficacy for stroke in man has never been demonstrated despite four phase III trials.

Citicoline and lithium significantly increased the survival of RGCs following crush injury Citicoline and lithium significantly increased the survival of RGCs following crush injury

Surprisingly, the manuscript never references a fascinating body of literature in which citicoline was found to have a beneficial effect on perimetric or electrophysiological findings in longitudinal human glaucoma studies.^1-3 Regarding lithium, although the authors refer to the previous work by⁴ which demonstrates that lithium facilitates ganglion cell survival by upregulating Bcl-2, there is surprising omission of references to the other well known mechanisms by which lithium neuroprotection has been shown to occur; namely through the PI 3-kinase/Akt signaling pathway and the induction of neurotrophic/neuroprotective proteins including brain-derived neurotrophic factor and heat-shock protein in addition to Bcl-2.⁵

However, the continued in vitro and in vivo work shown by the authors in this paper, combined with the insights into the specific signal transduction pathways elicited by drugs such as citicoline and lithium, may pave the way for future compounds that one day will hopefully provide the robust protection necessary to achieve these labeling claims.

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