Abstract
Cytidine 5’-diphosphocholine has been widely studied in systemic neurodegenerative diseases, like Alzheimer’s disease, Parkinson’s disease, and brain ischemia. The rationale for the use of citicoline in ophthalmological neurodegenerative diseases, including glaucoma, anterior ischemic optic neuropathy, and diabetic retinopathy, is founded on its multifactorial mechanism of action and the involvement in several metabolic pathways, including phospholipid homeostasis, mitochondrial dynamics, as well as cholinergic and dopaminergic transmission, all being involved in the complexity of the visual transmission. This narrative review is aimed at reporting both pre-clinical data regarding the involvement of citicoline in such metabolic pathways (including new insights about its role in the intracellular proteostasis through an interaction with the proteasome) and its effects on clinical psychophysical, electrophysiological, and morphological outcomes following its use in ophthalmological neurodegenerative diseases (including the results of the most recent prospective randomized clinical trials).
Highlights
Published: 20 March 2021Retinal ganglion cells (RGCs) bodies reside in the ganglion cell layer of the inner retina and their axons run above them in the retinal nerve fiber layer to constitute the optic nerve, which brings visual input to the cerebral structure [1].RGCs may be affected in several pathologies of the visual system, like glaucoma, optic neuritis, and diabetic retinopathy.Open Angle Glaucoma (OAG) is characterized by a loss of all RGCs compartments: somata, axons, and dendrites
Preclinical data will be discussed in this review as the rationale for the use of citicoline in human pathologies involving RGCs and clinical studies that validated the effect of citicoline in ophthalmological neurodegenerative diseases, like OAG, anterior ischemic optic neuropathy (AION), and diabetic retinopathy (DR)
The rationale for the use of citicoline in ophthalmological neurodegenerative diseases is founded on its multifactorial mechanism of action and the involvement in several metabolic pathways including phospholipid homeostasis, mitochondrial dynamics as well as cholinergic and dopaminergic transmission, as reported in several pre-clinical studies
Summary
Retinal ganglion cells (RGCs) bodies reside in the ganglion cell layer of the inner retina and their axons run above them in the retinal nerve fiber layer to constitute the optic nerve, which brings visual input to the cerebral structure [1]. In diabetic retinopathy (DR), neurodegeneration is the primary event, and it may precede the development of the characteristic microvascular complications [7] The targets of this neurodegenerative process are the RGCs and amacrine cells with consequent structural thinning of retinal neuronal and axonal layers at macula [8]. Citicoline stimulates the biosynthesis of sphingomyelin, a key lipidic metabolite that contributes to the stabilization of plasma membrane of RGC axons This property further helps the cells to inhibit the release of free fatty acids and it confers additional protection toward redox imbalance, through improved scavenging properties, and to-ward the release of neuroinflammation modulators [15]. Citicoline prevents ischemia-induced tissue accumulation of free fatty acids and reduces infarct volume and brain edema, resulting in an antiapoptotic effect that is related to mitochondrial dependent cell death mechanism [22,23]. Preclinical data will be discussed in this review as the rationale for the use of citicoline in human pathologies involving RGCs and clinical studies (reporting psychophysical, morphological, and electrophysiological evidences) that validated the effect of citicoline in ophthalmological neurodegenerative diseases, like OAG, AION, and DR
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