Citicoline and Retinal Ganglion Cells: Effects on Morphology and Function

Vincenzo Parisi, Francesco Oddone, Lucia Ziccardi, Gloria Roberti, Gianluca Coppola, Gianluca Manni, Vincenzo Parisi, Francesco Oddone, Lucia Ziccardi, Gloria Roberti, Gianluca Coppola, Gianluca Manni

Abstract

Background: Retinal ganglion cells (RGCs) are the nervous retinal elements which connect the visual receptors to the brain forming the nervous visual system. Functional and/or morphological involvement of RGCs occurs in several ocular and neurological disorders and therefore these cells are targeted in neuroprotective strategies. Cytidine 5-diphosphocholine or Citicoline is an endogenous compound that acts in the biosynthesis of phospholipids of cell membranes and increases neurotransmitters' levels in the Central Nervous System. Experimental studies suggested the neuromodulator effect and the protective role of Citicoline on RGCs. This review aims to present evidence of the effects of Citicoline in experimental models of RGCs degeneration and in human neurodegenerative disorders involving RGCs.

Methods: All published papers containing experimental or clinical studies about the effects of Citicoline on RGCs morphology and function were reviewed.

Results: In rodent retinal cultures and animal models, Citicoline induces antiapoptotic effects, increases the dopamine retinal level, and counteracts retinal nerve fibers layer thinning. Human studies in neurodegenerative visual pathologies such as glaucoma or non-arteritic ischemic neuropathy showed a reduction of the RGCs impairment after Citicoline administration. By reducing the RGCs' dysfunction, a better neural conduction along the post-retinal visual pathways with an improvement of the visual field defects was observed.

Conclusion: Citicoline, with a solid history of experimental and clinical studies, could be considered a very promising molecule for neuroprotective strategies in those pathologies (i.e. Glaucoma) in which morpho-functional changes of RGCc occurs.

Keywords: Retinal ganglion cells; citicoline; glaucoma; ischemic optic neuropathy; neurodegeneration; neuroprotection; pattern electroretinogram..

Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

References

    1. Sadun A.A., Glaser J.S. 1999. Anatomy of the visual sensory system.
    1. Carelli V., Ross-Cisneros F.N., Sadun A.A. Mitochondrial dysfunction as a cause of optic neuropathies. Prog. Retin. Eye Res. 2004;23(1):53–89. [. 10.003]. [PMID: 14766317].
    1. Newman N.J. Optic neuropathy. Neurology. 1996;46(2):315–322. []. [PMID: 8614487].
    1. Carelli V., Barboni P., Sadun A.A. 2006.
    1. Carelli V., La Morgia C., Iommarini L., Carroccia R., Mattiazzi M., Sangiorgi S., Farnè’ S., Maresca A., Foscarini B., Lanzi L., Amadori M., Bellan M., Valentino M.L. Mitochondrial optic neuropathies: how two genomes may kill the same cell type? Biosci. Rep. 2007;27(1-3):173–184. [ s10540-007-9045-0]. [PMID: 17479363].
    1. Yu W.M. C.Y.; Chinnery, P.F.; Griffiths, P.G. Optic neuropathies--importance of spatial distribution of mitochondria as well as function. Med. Hypotheses. 2005;65(6):1038–1042. [http://dx.doi. org/10.1016/j.mehy.2004.10.021]. [PMID: 16098682].
    1. Leber T. Uber hereditare und congenital-angelegte Sehnervenleiden. Arch. Ophthalmol. 1871;17:249–291.
    1. Wallace D.C., Singh G., Lott M.T., Hodge J.A., Schurr T.G., Lezza A.M., Elsas L.J., II, Nikoskelainen E.K. Mitochondrial DNA mutation associated with Leber’s hereditary optic neuropathy. Science. 1988;242(4884):1427–1430. [. 1126/science.3201231]. [PMID: 3201231].
    1. Kjer P. Infantile optic atrophy with dominant mode of inheritance: a clinical and genetic study of 19 Danish families. Acta Ophthalmol. Suppl. 1959;164(Suppl. 54):1–147. [PMID: 13660776].
    1. Alexander C., Votruba M., Pesch U.E.A., Thiselton D.L., Mayer S., Moore A., Rodriguez M., Kellner U., Leo-Kottler B., Auburger G., Bhattacharya S.S., Wissinger B. OPA1, encoding a dynamin-related GTPase, is mutated in autosomal dominant optic atrophy linked to chromosome 3q28. Nat. Genet. 2000;26(2):211–215. []. [PMID: 11017080].
    1. Delettre C., Lenaers G., Griffoin J-M., Gigarel N., Lorenzo C., Belenguer P., Pelloquin L., Grosgeorge J., Turc-Carel C., Perret E., Astarie-Dequeker C., Lasquellec L., Arnaud B., Ducommun B., Kaplan J., Hamel C.P. Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy. Nat. Genet. 2000;26(2):207–210. [. 1038/79936]. [PMID: 11017079].
    1. Yu-Wai-Man P., Griffiths P.G., Brown D.T., Howell N., Turnbull D.M., Chinnery P.F. The epidemiology of Leber hereditary optic neuropathy in the North East of England. Am. J. Hum. Genet. 2003;72(2):333–339. []. [PMID: 12518276].
    1. Yu-Wai-Man P., Griffiths P.G., Hudson G., Chinnery P.F. Inherited mitochondrial optic neuropathies. J. Med. Genet. 2009;46(3):145–158. []. [PMID: 19001017].
    1. Lüdtke H., Kriegbaum C., Leo-Kottler B., Wilhelm H. Pupillary light reflexes in patients with Leber’s hereditary optic neuropathy. Graefes Arch. Clin. Exp. Ophthalmol. 1999;237(3):207–211. []. [PMID: 10090583].
    1. Bose S., Dhillon N., Ross-Cisneros F.N., Carelli V. Relative post-mortem sparing of afferent pupil fibers in a patient with 3460 Leber’s hereditary optic neuropathy. Graefes Arch. Clin. Exp. Ophthalmol. 2005;243(11):1175–1179. [ s00417-005-0023-6]. [PMID: 16003516].
    1. Sadun A.A., Kashima Y., Wurdeman A.E., Dao J., Heller K., Sherman J. Morphological findings in the visual system in a case of Leber’s hereditary optic neuropathy. Clin. Neurosci. 1994;2:165–172.
    1. Sadun A.A., Win P.H., Ross-Cisneros F.N., Walker S.O., Carelli V. Leber’s hereditary optic neuropathy differentially affects smaller axons in the optic nerve. Trans. Am. Ophthalmol. Soc. 2000;98:223–232. [PMID: 11190025].
    1. Ziccardi L., Sadun F., De Negri A.M., Barboni P., Savini G., Borrelli E., La Morgia C., Carelli V., Parisi V. Retinal function and neural conduction along the visual pathways in affected and unaffected carriers with Leber’s hereditary optic neuropathy. Invest. Ophthalmol. Vis. Sci. 2013;54(10):6893–6901. [http://dx.doi. org/10.1167/iovs.13-12894]. [PMID: 24071953].
    1. Ziccardi L., Parisi V., Giannini D., Sadun F., De Negri A.M., Barboni P., La Morgia C., Sadun A.A., Carelli V. Multifocal VEP provide electrophysiological evidence of predominant dysfunction of the optic nerve fibers derived from the central retina in Leber’s hereditary optic neuropathy. Graefes Arch. Clin. Exp. Ophthalmol. 2015;253(9):1591–1600. [ s00417-015-2979-1]. [PMID: 25773998].
    1. Delettre C., Lenaers G., Pelloquin L., Belenguer P., Hamel C.P. OPA1 (Kjer type) dominant optic atrophy: a novel mitochondrial disease. Mol. Genet. Metab. 2002;75(2):97–107. [http://dx.doi. org/10.1006/mgme.2001.3278]. [PMID: 11855928].
    1. Cohn A.C., Toomes C., Hewitt A.W., Kearns L.S., Inglehearn C.F., Craig J.E., Mackey D.A. The natural history of OPA1-related autosomal dominant optic atrophy. Br. J. Ophthalmol. 2008;92(10):1333–1336. [. 134726]. [PMID: 18653586].
    1. Votruba M., Thiselton D., Bhattacharya S.S. Optic disc morphology of patients with OPA1 autosomal dominant optic atrophy. Br. J. Ophthalmol. 2003;87(1):48–53. [ bjo.87.1.48]. [PMID: 12488262].
    1. Kjer P., Jensen O.A., Klinken L. Histopathology of eye, optic nerve and brain in a case of dominant optic atrophy. Acta Ophthalmol. (Copenh.) 1983;61(2):300–312. [ j.1755-3768.1983.tb01424.x]. [PMID: 6880639].
    1. Quigley H.A. Glaucoma. Lancet. 2011;377(9774):1367–1377. [http:// ]. [PMID: 21453963].
    1. Quigley H.A., Nickells R.W., Kerrigan L.A., Pease M.E., Thibault D.J., Zack D.J. Retinal ganglion cell death in experimental glaucoma and after axotomy occurs by apoptosis. Invest. Ophthalmol. Vis. Sci. 1995;36(5):774–786. [PMID: 7706025].
    1. Gupta N., Ang L.C., Noël de Tilly L., Bidaisee L., Yücel Y.H. Human glaucoma and neural degeneration in intracranial optic nerve, lateral geniculate nucleus, and visual cortex. Br. J. Ophthalmol. 2006;90(6):674–678. []. [PMID: 16464969].
    1. Leske M.C., Heijl A., Hyman L., Bengtsson B., Dong L., Yang Z. Predictors of long-term progression in the early manifest glaucoma trial. Ophthalmology. 2007;114(11):1965–1972. [http://dx. ]. [PMID: 17628686].
    1. The Advanced Glaucoma Intervention Study (AGIS) 7. The relationship between control of intraocular pressure and visual field deterioration. Am. J. Ophthalmol. 2000;130(4):429–440. [http://dx. ]. [PMID: 11024415].
    1. Anderson D.R., Drance S.M., Schulzer M. Comparison of glaucomatous progression between untreated patients with normal-tension glaucoma and patients with therapeutically reduced intraocular pressures. Am. J. Ophthalmol. 1998;126(4):487–497. [http:// ]. [PMID: 9780093].
    1. Li H.Y., Ruan Y.W., Ren C.R., Cui Q., So K.F. Mechanisms of secondary degeneration after partial optic nerve transection. Neural Regen. Res. 2014;9(6):565–574. []. [PMID: 25206855].
    1. Kerrigan-Baumrind L.A., Quigley H.A., Pease M.E., Kerrigan D.F., Mitchell R.S. Number of ganglion cells in glaucoma eyes compared with threshold visual field tests in the same persons. Invest. Ophthalmol. Vis. Sci. 2000;41(3):741–748. [PMID: 10711689].
    1. Anderson D.R., Hendrickson A. Effect of intraocular pressure on rapid axoplasmic transport in monkey optic nerve. Invest. Ophthalmol. 1974;13(10):771–783. [PMID: 4137635].
    1. Yamamoto T., Kitazawa Y. Vascular pathogenesis of normal-tension glaucoma: a possible pathogenetic factor, other than intraocular pressure, of glaucomatous optic neuropathy. Prog. Retin. Eye Res. 1998;17(1):127–143. []. [PMID: 9537793].
    1. Flammer J. The vascular concept of glaucoma. Surv. Ophthalmol. 1994;38(Suppl.):S3–S6. [ 90041-8]. [PMID: 7940146].
    1. Deng S., Wang M., Yan Z., Tian Z., Chen H., Yang X., Zhuo Y. Autophagy in retinal ganglion cells in a rhesus monkey chronic hypertensive glaucoma model. PLoS One. 2013;8(10):e77100. []. [PMID: 24143204].
    1. Kleesattel D., Crish S.D.I.D., Inman D.M., Crish S.D., Inman D.M., Kleesattel D. Decreased energy capacity and increased autophagic activity in optic nerve axons with defective anterograde transport. Invest. Ophthalmol. Vis. Sci. 2015;56(13):8215–8227. []. [PMID: 26720474].
    1. Kroemer G., Mariño G., Levine B. Autophagy and the integrated stress response. Mol. Cell. 2010;40(2):280–293. [http://dx.doi. org/10.1016/j.molcel.2010.09.023]. [PMID: 20965422].
    1. Nixon R.A. The role of autophagy in neurodegenerative disease. Nat. Med. 2013;19(8):983–997. [. 3232]. [PMID: 23921753].
    1. Guo L., Salt T.E., Luong V., Wood N., Cheung W., Maass A., Ferrari G., Russo-Marie F., Sillito A.M., Cheetham M.E.
    2. Moss S.E., Fitzke F.W., Cordeiro M.F. Targeting amyloid-beta in glaucoma treatment. Proc. Natl. Acad. Sci. USA. 2007;104(33):13444–13449. []. [PMID: 17684098].
    1. Jonas J.B., Wang N., Yang D., Ritch R., Panda-Jonas S. Facts and myths of cerebrospinal fluid pressure for the physiology of the eye. Prog. Retin. Eye Res. 2015;46:67–83. [. 1016/j.preteyeres.2015.01.002]. [PMID: 25619727].
    1. Jonas J.B., Berenshtein E., Holbach L. Anatomic relationship between lamina cribrosa, intraocular space, and cerebrospinal fluid space. Invest. Ophthalmol. Vis. Sci. 2003;44(12):5189–5195. []. [PMID: 14638716].
    1. Wostyn P., Van Dam D., Audenaert K., Killer H.E., De Deyn P.P., De Groot V. A new glaucoma hypothesis: a role of glymphatic system dysfunction. Fluids Barriers CNS. 2015;12:16. []. [PMID: 26118970].
    1. Hayreh S.S. Ischemic optic neuropathy. Prog. Retin. Eye Res. 2009;28(1):34–62. [. 11.002]. [PMID: 19063989].
    1. Bernstein S.L., Guo Y., Kelman S.E., Flower R.W., Johnson M.A. Functional and cellular responses in a novel rodent model of anterior ischemic optic neuropathy. Invest. Ophthalmol. Vis. Sci. 2003;44(10):4153–4162. []. [PMID: 14507856].
    1. Parisi V., Coppola G., Ziccardi L., Gallinaro G., Falsini B. Cytidine-5′-diphosphocholine (Citicoline): a pilot study in patients with non-arteritic ischaemic optic neuropathy. Eur. J. Neurol. 2008;15(5):465–474. [. 02099.x]. [PMID: 18325025].
    1. Barber A.J., Gardner T.W., Abcouwer S.F. The significance of vascular and neural apoptosis to the pathology of diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 2011;52(2):1156–1163. [http:// ]. [PMID: 21357409].
    1. Barber A.J., Lieth E., Khin S.A., Antonetti D.A., Buchanan A.G., Gardner T.W. Neural apoptosis in the retina during experimental and human diabetes. Early onset and effect of insulin. J. Clin. Invest. 1998;102(4):783–791. [ JCI2425]. [PMID: 9710447].
    1. Aizu Y., Oyanagi K., Hu J., Nakagawa H. Degeneration of retinal neuronal processes and pigment epithelium in the early stage of the streptozotocin-diabetic rats. Neuropathology. 2002;22(3):161–170. []. [PMID: 12416555].
    1. van Dijk H.W., Verbraak F.D., Kok P.H., Garvin M.K., Sonka M., Lee K., Devries J.H., Michels R.P., van Velthoven M.E., Schlingemann R.O., Abràmoff M.D. Decreased retinal ganglion cell layer thickness in patients with type 1 diabetes. Invest. Ophthalmol. Vis. Sci. 2010;51(7):3660–3665. [. 1167/iovs.09-5041]. [PMID: 20130282].
    1. van Dijk H.W., Verbraak F.D., Kok P.H., Stehouwer M., Garvin M.K., Sonka M., DeVries J.H., Schlingemann R.O., Abràmoff M.D. Early neurodegeneration in the retina of type 2 diabetic patients. Invest. Ophthalmol. Vis. Sci. 2012;53(6):2715–2719. []. [PMID: 22427582].
    1. van Dijk H.W., Kok P.H., Garvin M., Sonka M., Devries J.H., Michels R.P., van Velthoven M.E., Schlingemann R.O., Verbraak F.D., Abràmoff M.D. Selective loss of inner retinal layer thickness in type 1 diabetic patients with minimal diabetic retinopathy. Invest. Ophthalmol. Vis. Sci. 2009;50(7):3404–3409. []. [PMID: 19151397].
    1. Vujosevic S., Midena E. Retinal layers changes in human preclinical and early clinical diabetic retinopathy support early retinal neuronal and Müller cells alterations. J. Diabetes Res. 2013;2013:905058. []. [PMID: 23841106].
    1. Araszkiewicz A., Zozulińska-Ziółkiewicz D., Meller M., Bernardczyk-Meller J., Piłaciński S., Rogowicz-Frontczak A., Naskręt D., Wierusz-Wysocka B. Neurodegeneration of the retina in type 1 diabetic patients. Pol. Arch. Med. Wewn. 2012;122(10):464–470. []. [PMID: 22910230].
    1. Demir M., Oba E., Sensoz H., Ozdal E. Retinal nerve fiber layer and ganglion cell complex thickness in patients with type 2 diabetes mellitus. Indian J. Ophthalmol. 2014;62(6):719–720. []. [PMID: 25005202].
    1. Park H.Y., Kim I.T., Park C.K. Early diabetic changes in the nerve fibre layer at the macula detected by spectral domain optical coherence tomography. Br. J. Ophthalmol. 2011;95(9):1223–1228. []. [PMID: 21216799].
    1. Ng D.S., Chiang P.P., Tan G., Cheung C.G., Cheng C.Y., Cheung C.Y., Wong T.Y., Lamoureux E.L., Ikram M.K. Retinal ganglion cell neuronal damage in diabetes and diabetic retinopathy. Clin. Experiment. Ophthalmol. 2016;44(4):243–250. [http://dx. ]. [PMID: 26872562].
    1. Parisi V., Uccioli L., Monticone G., Parisi L., Manni G., Ippoliti D., Menzinger G., Bucci M.G. Electrophysiological assessment of visual function in IDDM patients. Electroencephalogr. Clin. Neurophysiol. 1997;104(2):171–179. [ 10.1016/S0168-5597(97)96606-5]. [PMID: 9146484].
    1. Parisi V., Uccioli L. Visual electrophysiological responses in persons with type 1 diabetes. Diabetes Metab. Res. Rev. 2001;17(1):12–18. []. [PMID: 11241887].
    1. Parisi V., Uccioli L., Parisi L., Colacino G., Manni G., Menzinger G., Bucci M.G. Neural conduction in visual pathways in newly-diagnosed IDDM patients. Electroencephalogr. Clin. Neurophysiol. 1998;108(5):490–496. [ S0168-5597(98)00026-4]. [PMID: 9780019].
    1. Uccioli L., Parisi V., Monticone G., Parisi L., Durola L., Pernini C., Neuschuler R., Bucci M.G., Menzinger G. Electrophysiological assessment of visual function in newly-diagnosed IDDM patients. Diabetologia. 1995;38(7):804–808. [. 1007/s001250050356]. [PMID: 7556982].
    1. Petzold A., de Boer J.F., Schippling S., Vermersch P., Kardon R., Green A., Calabresi P.A., Polman C. Optical coherence tomography in multiple sclerosis: a systematic review and meta-analysis. Lancet Neurol. 2010;9(9):921–932. [ 10.1016/S1474-4422(10)70168-X]. [PMID: 20723847].
    1. Johnson H., Cowey A. Transneuronal retrograde degeneration of retinal ganglion cells following restricted lesions of striate cortex in the monkey. Exp. Brain Res. 2000;132(2):269–275. [http://dx. ]. [PMID: 10853951].
    1. Weller R.E., Kaas J.H. Parameters affecting the loss of ganglion cells of the retina following ablations of striate cortex in primates. Vis. Neurosci. 1989;3(4):327–349. [ S0952523800005514]. [PMID: 2487111].
    1. Cowey A., Alexander I., Stoerig P. Transneuronal retrograde degeneration of retinal ganglion cells and optic tract in hemianopic monkeys and humans. Brain. 2011;134(Pt 7):2149–2157. []. [PMID: 21705429].
    1. Gabilondo I., Martínez-Lapiscina E.H., Martínez-Heras E., Fraga-Pumar E., Llufriu S., Ortiz S., Bullich S., Sepulveda M., Falcon C., Berenguer J., Saiz A., Sanchez-Dalmau B., Villoslada P. Trans-synaptic axonal degeneration in the visual pathway in multiple sclerosis. Ann. Neurol. 2014;75(1):98–107. []. [PMID: 24114885].
    1. Sriram P., Wang C., Yiannikas C., Garrick R., Barnett M., Parratt J., Graham S.L., Arvind H., Klistorner A. Relationship between optical coherence tomography and electrophysiology of the visual pathway in non-optic neuritis eyes of multiple sclerosis patients. PLoS One. 2014;9(8):e102546. [. 1371/journal.pone.0102546]. [PMID: 25166273].
    1. Stefano E., Cupini L.M., Rizzo P., Pierelli F., Rizzo P.A. Simultaneous recording of pattern electroretinogram (PERG) and visual evoked potential (VEP) in multiple sclerosis. Acta Neurol. Belg. 1991;91(1):20–28. [PMID: 2028736].
    1. Parisi V., Manni G., Spadaro M., Colacino G., Restuccia R., Marchi S., Bucci M.G., Pierelli F. Correlation between morphological and functional retinal impairment in multiple sclerosis patients. Invest. Ophthalmol. Vis. Sci. 1999;40(11):2520–2527. [PMID: 10509645].
    1. Hinton D.R., Sadun A.A., Blanks J.C., Miller C.A. Optic-nerve degeneration in Alzheimer’s disease. N. Engl. J. Med. 1986;315(8):485–487. []. [PMID: 3736630].
    1. Blanks J.C., Torigoe Y., Hinton D.R., Blanks R.H. Retinal pathology in Alzheimer’s disease. I. Ganglion cell loss in foveal/ parafoveal retina. Neurobiol. Aging. 1996;17(3):377–384. [http:// ]. [PMID: 8725899].
    1. Kergoat H., Kergoat M.J., Justino L., Chertkow H., Robillard A., Bergman H. An evaluation of the retinal nerve fiber layer thickness by scanning laser polarimetry in individuals with dementia of the Alzheimer type. Acta Ophthalmol. Scand. 2001;79(2):187–191. [. x]. [PMID: 11284761].
    1. Danesh-Meyer H.V., Birch H., Ku J.Y., Carroll S., Gamble G. Reduction of optic nerve fibers in patients with Alzheimer disease identified by laser imaging. Neurology. 2006;67(10):1852–1854. []. [PMID: 17130422].
    1. Berisha F., Feke G.T., Trempe C.L., McMeel J.W., Schepens C.L. Retinal abnormalities in early Alzheimer’s disease. Invest. Ophthalmol. Vis. Sci. 2007;48(5):2285–2289. [ 10.1167/iovs.06-1029]. [PMID: 17460292].
    1. Lu Y., Li Z., Zhang X., Ming B., Jia J., Wang R., Ma D. Retinal nerve fiber layer structure abnormalities in early Alzheimer’s disease: evidence in optical coherence tomography. Neurosci. Lett. 2010;480(1):69–72. [. 006]. [PMID: 20609426].
    1. Kesler A., Vakhapova V., Korczyn A.D., Naftaliev E., Neudorfer M. Retinal thickness in patients with mild cognitive impairment and Alzheimer’s disease. Clin. Neurol. Neurosurg. 2011;113(7):523–526. []. [PMID: 21454010].
    1. Kirbas S., Turkyilmaz K., Anlar O., Tufekci A., Durmus M. Retinal nerve fiber layer thickness in patients with Alzheimer disease. J. Neuroophthalmol. 2013;33(1):58–61. [ 10.1097/WNO.0b013e318267fd5f]. [PMID: 22918296].
    1. Parisi V., Restuccia R., Fattapposta F., Mina C., Bucci M.G., Pierelli F. Morphological and functional retinal impairment in Alzheimer’s disease patients. Clin. Neurophysiol. 2001;112(10):1860–1867. []. [PMID: 11595144].
    1. Cheung C.Y., Ong Y.T., Hilal S., Ikram M.K., Low S., Ong Y.L., Venketasubramanian N., Yap P., Seow D., Chen C.L., Wong T.Y. Retinal ganglion cell analysis using high-definition optical coherence tomography in patients with mild cognitive impairment and Alzheimer’s disease. J. Alzheimers Dis. 2015;45(1):45–56. [PMID: 25428254].
    1. Parisi V. Correlation between morphological and functional retinal impairment in patients affected by ocular hypertension, glaucoma, demyelinating optic neuritis and Alzheimer’s disease. Semin. Ophthalmol. 2003;18(2):50–57. [PMID: 14566623].
    1. Harwerth R.S., Carter-Dawson L., Shen F., Smith E.L., III, Crawford M.L. Ganglion cell losses underlying visual field defects from experimental glaucoma. Invest. Ophthalmol. Vis. Sci. 1999;40(10):2242–2250. [PMID: 10476789].
    1. Harwerth R.S., Wheat J.L., Fredette M.J., Anderson D.R. Linking structure and function in glaucoma. Prog. Retin. Eye Res. 2010;29(4):249–271. [. 02.001]. [PMID: 20226873].
    1. Quigley H.A., Dunkelberger G.R., Green W.R. Retinal ganglion cell atrophy correlated with automated perimetry in human eyes with glaucoma. Am. J. Ophthalmol. 1989;107(5):453–464. [http:// ]. [PMID: 2712129].
    1. Harwerth R.S., Quigley H.A. Visual field defects and retinal ganglion cell losses in patients with glaucoma. Arch. Ophthalmol. 2006;124(6):853–859. [. 6.853]. [PMID: 16769839].
    1. Mafei L., Fiorentini A. Electroretinographic responses to alternating gratings before and after section of the optic nerve. Science. 1981;211(4485):953–955. [. 7466369]. [PMID: 7466369].
    1. Parisi V. Neural conduction in the visual pathways in ocular hypertension and glaucoma. Graefes Arch. Clin. Exp. Ophthalmol. 1997;235(3):136–142. []. [PMID: 9085108].
    1. Parisi V., Pernini C., Guinetti C., Neuschuler R., Bucci M.G. Electrophysiological assessment of visual pathways in glaucoma. Eur. J. Ophthalmol. 1997;7(3):229–235. [. 1177/112067219700700305]. [PMID: 9352275].
    1. Parisi V. Impaired visual function in glaucoma. Clin. Neurophysiol. 2001;112(2):351–358. []. [PMID: 11165541].
    1. Parisi V., Miglior S., Manni G., Centofanti M., Bucci M.G. Clinical ability of pattern electroretinograms and visual evoked potentials in detecting visual dysfunction in ocular hypertension and glaucoma. Ophthalmology. 2006;113(2):216–228. [http://dx.doi. org/10.1016/j.ophtha.2005.10.044]. [PMID: 16406535].
    1. Porciatti V. Electrophysiological assessment of retinal ganglion cell function. Exp. Eye Res. 2015;141:164–170. [ 10.1016/j.exer.2015.05.008]. [PMID: 25998495].
    1. Fortune B., Hardin C., Reynaud J., Cull G., Yang H., Wang L., Burgoyne C.F. Comparing optic nerve head rim width, rim area, and peripapillary retinal nerve fiber layer thickness to axon count in experimental glaucoma. Invest. Ophthalmol. Vis. Sci. 2016;57(9):404–OCT412. []. [PMID: 27409499].
    1. Cull G.A., Reynaud J., Wang L., Cioffi G.A., Burgoyne C.F., Fortune B. Relationship between orbital optic nerve axon counts and retinal nerve fiber layer thickness measured by spectral domain optical coherence tomography. Invest. Ophthalmol. Vis. Sci. 2012;53(12):7766–7773. []. [PMID: 23125332].
    1. Barboni P., Savini G., Valentino M.L., Montagna P., Cortelli P., De Negri A.M., Sadun F., Bianchi S., Longanesi L., Zanini M., de Vivo A., Carelli V. Retinal nerve fiber layer evaluation by optical coherence tomography in Leber’s hereditary optic neuropathy. Ophthalmology. 2005;112(1):120–126. [. 1016/j.ophtha.2004.06.034]. [PMID: 15629831].
    1. Savini G., Zanini M., Carelli V., Sadun A.A., Ross-Cisneros F.N., Barboni P. Correlation between retinal nerve fibre layer thickness and optic nerve head size: an optical coherence tomography study. Br. J. Ophthalmol. 2005;89(4):489–492. [http://dx. ]. [PMID: 15774930].
    1. Curcio C.A., Allen K.A. Topography of ganglion cells in human retina. J. Comp. Neurol. 1990;300(1):5–25. [. 1002/cne.903000103]. [PMID: 2229487].
    1. You Y., Gupta V.K., Li J.C., Klistorner A., Graham S.L. Optic neuropathies: characteristic features and mechanisms of retinal ganglion cell loss. Rev. Neurosci. 2013;24(3):301–321. []. [PMID: 23612594].
    1. Chang E.E., Goldberg J.L. Glaucoma 2.0: neuroprotection, neuroregeneration, neuroenhancement. Ophthalmology. 2012;119(5):979–986. []. [PMID: 22349567].
    1. Kimura A., Namekata K., Guo X., Harada C., Harada T. Neuroprotection, Growth Factors and BDNF-TrkB Signalling in Retinal Degeneration. Int. J. Mol. Sci. 2016;17(9):17. [ 10.3390/ijms17091584]. [PMID: 27657046].
    1. Miguel-Hidalgo J.J., Alvarez X.A., Cacabelos R., Quack G. Neuroprotection by memantine against neurodegeneration induced by beta-amyloid(1-40). Brain Res. 2002;958(1):210–221. [http:// ]. [PMID: 12468047].
    1. Ritch R. Potential role for Ginkgo biloba extract in the treatment of glaucoma. Med. Hypotheses. 2000;54(2):221–235. [http://dx. ]. [PMID: 10790757].
    1. Stout A.K., Raphael H.M., Kanterewicz B.I., Klann E., Reynolds I.J. Glutamate-induced neuron death requires mitochondrial calcium uptake. Nat. Neurosci. 1998;1(5):366–373. [http://dx.doi. org/10.1038/1577]. [PMID: 10196525].
    1. Crish S.D., Calkins D.J. Neurodegeneration in glaucoma: progression and calcium-dependent intracellular mechanisms. Neuroscience. 2011;176:1–11. [. 2010.12.036]. [PMID: 21187126].
    1. Doozandeh A., Yazdani S. Neuroprotection in Glaucoma. J. Ophthalmic Vis. Res. 2016;11(2):209–220. [. 4103/2008-322X.183923]. [PMID: 27413504].
    1. Kalapesi F.B., Coroneo M.T., Hill M.A. Human ganglion cells express the alpha-2 adrenergic receptor: relevance to neuroprotection. Br. J. Ophthalmol. 2005;89(6):758–763. [ 10.1136/bjo.2004.053025]. [PMID: 15923515].
    1. Park S.H., Kim J.H., Kim Y.H., Park C.K. Expression of neuronal nitric oxide synthase in the retina of a rat model of chronic glaucoma. Vision Res. 2007;47(21):2732–2740. [http://dx.doi. org/10.1016/j.visres.2007.07.011]. [PMID: 17825345].
    1. Dahlmann-Noor A., Vijay S., Jayaram H., Limb A., Khaw P.T. Current approaches and future prospects for stem cell rescue and regeneration of the retina and optic nerve. Can. J. Ophthalmol. 2010;45(4):333–341. []. [PMID: 20648090].
    1. Rejdak R., Toczołowski J., Solski J., Duma D., Grieb P. Citicoline treatment increases retinal dopamine content in rabbits. Ophthalmic Res. 2002;34(3):146–149. [ 000063658]. [PMID: 12097797].
    1. Schuettauf F., Rejdak R., Thaler S., Bolz S., Lehaci C., Mankowska A., Zarnowski T., Junemann A., Zagorski Z., Zrenner E., Grieb P. Citicoline and lithium rescue retinal ganglion cells following partial optic nerve crush in the rat. Exp. Eye Res. 2006;83(5):1128–1134. [. 021]. [PMID: 16876158].
    1. Park C.H., Kim Y.S., Noh H.S., Cheon E.W., Yang Y.A., Yoo J.M., Choi W.S., Cho G.J. Neuroprotective effect of citicoline against KA-induced neurotoxicity in the rat retina. Exp. Eye Res. 2005;81(3):350–358. [. 007]. [PMID: 16129102].
    1. Oshitari T., Fujimoto N., Adachi-Usami E. Citicoline has a protective effect on damaged retinal ganglion cells in mouse culture retina. Neuroreport. 2002;13(16):2109–2111. [ 10.1097/00001756-200211150-00023]. [PMID: 12438935].
    1. Oshitari T., Yoshida-Hata N., Yamamoto S. Effect of neurotrophic factors on neuronal apoptosis and neurite regeneration in cultured rat retinas exposed to high glucose. Brain Res. 2010;1346:43–51. []. [PMID: 20573599].
    1. 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(4):6286–6297. [ 15046286]. [PMID: 24736780].
    1. Zerbini G., Bandello F., Lattanzio R., Gabellini D., Zucchiatti I., Spinello A., Capuano V., Preziosa C., Maestroni S. In vivo evaluation of retinal and choroidal structure in a mouse model of long-lasting diabetes. Effect of topical treatment with citicoline. J. Ocul. Dis. Ther. 2015;3:1–8. [].
    1. Secades J.J. Citicoline: pharmacological and clinical review, 2010 update. Rev. Neurol. 2011;52(Suppl. 2):S1–S62. [PMID: 21432836].
    1. Citicoline. Monograph. Altern. Med. Rev. 2008;13(1):50–57. [PMID: 18377103].
    1. Grau T., Romero A., Sacristán A., Ortiz J.A. CDP-choline: acute toxicity study. Arzneimittelforschung. 1983;33(7A):1033–1034. [PMID: 6684459].
    1. Schauss A.G., Somfai-Relle S., Financsek I., Glavits R., Parent S.C., Endres J.R., Varga T., Szücs Z., Clewell A. Single- and repeated-dose oral toxicity studies of citicoline free-base (choline cytidine 5′-pyrophosphate) in Sprague-Dawley rats. Int. J. Toxicol. 2009;28(6):479–487. []. [PMID: 19966140].
    1. Grieb P. Neuroprotective properties of citicoline: facts, doubts and unresolved issues. CNS Drugs. 2014;28(3):185–193. [http://dx.doi. org/10.1007/s40263-014-0144-8]. [PMID: 24504829].
    1. Fagone P., Jackowski S. Phosphatidylcholine and the CDP-choline cycle. Biochim. Biophys. Acta. 2013;1831(3):523–532. []. [PMID: 23010477].
    1. Kennedy E.P. Metabolism of lipides. Annu. Rev. Biochem. 1957;26:119–148. []. [PMID: 13488391].
    1. Rao A.M., Hatcher J.F., Dempsey R.J. Does CDP-choline modulate phospholipase activities after transient forebrain ischemia? Brain Res. 2001;893(1-2):268–272. [ S0006-8993(00)03280-7]. [PMID: 11223016].
    1. Adibhatla R.M., Hatcher J.F. Citicoline mechanisms and clinical efficacy in cerebral ischemia. J. Neurosci. Res. 2002;70(2):133–139. []. [PMID: 12271462].
    1. McMurray W.C., Magee W.L. Phospholipid metabolism. Annu. Rev. Biochem. 1972;41(10):129–160. [ annurev.bi.41.070172.001021]. [PMID: 4570957].
    1. Martinet M., Fonlupt P., Pacheco H. Effects of cytidine-5′ diphosphocholine on norepinephrine, dopamine and serotonin synthesis in various regions of the rat brain. Arch. Int. Pharmacodyn. Ther. 1979;239(1):52–61. [PMID: 485720].
    1. Agut J., Ortiz J.A., Wurtman R.J. Cytidine (5′)diphosphocholine modulates dopamine K(+)-evoked release in striatum measured by microdialysis. Ann. N. Y. Acad. Sci. 2000;920:332–335. [http:// ]. [PMID: 11193174].
    1. Petkov V.D., Stancheva S.L., Tocuschieva L., Petkov V.V. Changes in brain biogenic monoamines induced by the nootropic drugs adafenoxate and meclofenoxate and by citicholine (experiments on rats). Gen. Pharmacol. 1990;21(1):71–75. [http://dx.doi. org/10.1016/0306-3623(90)90598-G]. [PMID: 2105261].
    1. Osborne N.N., Nesselhut T. Adrenaline: occurrence in the bovine retina. Neurosci. Lett. 1983;39(1):33–36. [. 1016/0304-3940(83)90161-1]. [PMID: 6633936].
    1. Hadjiconstantinou M., Cohen J., Neff N.H. Epinephrine: a potential neurotransmitter in retina. J. Neurochem. 1983;41(5):1440–1444. []. [PMID: 6619876].
    1. Hurtado O., Moro M.A., Cárdenas A., Sánchez V., Fernández-Tomé P., Leza J.C., Lorenzo P., Secades J.J., Lozano R., Dávalos A., Castillo J., Lizasoain I. Neuroprotection afforded by prior citicoline administration in experimental brain ischemia: effects on glutamate transport. Neurobiol. Dis. 2005;18(2):336–345. []. [PMID: 15686962].
    1. Alvarez X.A., Sampedro C., Lozano R., Cacabelos R. Citicoline protects hippocampal neurons against apoptosis induced by brain beta-amyloid deposits plus cerebral hypoperfusion in rats. Methods Find. Exp. Clin. Pharmacol. 1999;21(8):535–540. [http://dx. ]. [PMID: 10599052].
    1. Skripuletz T., Manzel A., Gropengießer K., Schäfer N., Gudi V., Singh V., Salinas Tejedor L., Jörg S., Hammer A., Voss E., Vulinovic F., Degen D., Wolf R., Lee D.H., Pul R., Moharregh-Khiabani D., Baumgärtner W., Gold R., Linker R.A., Stangel M. Pivotal role of choline metabolites in remyelination. Brain. 2015;138(Pt 2):398–413. []. [PMID: 25524711].
    1. Fioravanti M., Yanagi M. Cytidinediphosphocholine (CDP-choline) for cognitive and behavioural disturbances associated with chronic cerebral disorders in the elderly. Cochrane Database Syst. Rev. 2005;18(2):CD000269. [PMID: 15846601].
    1. Parisi V., Manni G., Colacino G., Bucci M.G. Cytidine-5′-diphosphocholine (citicoline) improves retinal and cortical responses in patients with glaucoma. Ophthalmology. 1999;106(6):1126–1134. []. [PMID: 10366081].
    1. Parisi V. Electrophysiological assessment of glaucomatous visual dysfunction during treatment with cytidine-5′-diphosphocholine (citicoline): a study of 8 years of follow-up. Doc. Ophthalmol. 2005;110(1):91–102. []. [PMID: 16249960].
    1. Virno M., Pecori-Giraldi J., Liguori A., De Gregorio F. The protective effect of citicoline on the progression of the perimetric defects in glaucomatous patients (perimetric study with a 10-year follow-up). Acta Ophthalmol. Scand. Suppl. 2000;232(232):56–57. []. [PMID: 11235540].
    1. Parisi V., Coppola G., Centofanti M., Oddone F., Angrisani A.M., Ziccardi L., Ricci B., Quaranta L., Manni G. Evidence of the neuroprotective role of citicoline in glaucoma patients. 2008.
    1. Agut J., Font E., Sacristán A., Ortiz J.A. Bioavailability of methyl-14C CDP-choline by oral route. Arzneimittelforschung. 1983;33(7A):1045–1047. [PMID: 6684463].
    1. Roda A., Fini A., Grigolo B., Scapini G. Routes of administration and serum levels of [Methyl-14C]-Cytidine-Diphosphocholine. Curr. Ther. Res. Clin. Exp. 1983;34:1049–1053.
    1. Ottobelli L., Manni G.L., Centofanti M., Iester M., Allevena F., Rossetti L. Citicoline oral solution in glaucoma: is there a role in slowing disease progression? Ophthalmologica. 2013;229(4):219–226. []. [PMID: 23615390].
    1. Morreale Bubella R., Carità S., Morreale Bubella D. Neuroprotezione del paziente con glaucoma cronico ad angolo aperto: ruolo della citicolina in soluzione orale. Ottica Fisiopatologica. 2011;16:171–177.
    1. Roberti G., Tanga L., Parisi V., Sampalmieri M., Centofanti M., Manni G. A preliminary study of the neuroprotective role of citicoline eye drops in glaucomatous optic neuropathy. Indian J. Ophthalmol. 2014;62(5):549–553. []. [PMID: 24881599].
    1. Parisi V., Centofanti M., Ziccardi L., Tanga L., Michelessi M., Roberti G., Manni G. Treatment with citicoline eye drops enhances retinal function and neural conduction along the visual pathways in open angle glaucoma. Graefes Arch. Clin. Exp. Ophthalmol. 2015;253(8):1327–1340. [ s00417-015-3044-9]. [PMID: 26004075].

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