Citicoline Oral Solution in Glaucoma: Is There a Role in Slowing Disease Progression?

Ottobelli, Laura; Manni, Gianluca; Centofanti, Marco; Iester, Michele; Allevena, F; Rossetti, Luca

doi:10.1159/000350496

Cited by 69 publications

(71 citation statements)

References 30 publications

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“…In summary, one drop (5 µL) of liposomal citicoline (2%) or vehicle (5 µL of 0.9% sodium chloride) were administered twice daily for 14 days. This protocol was similarto previously reports by our group in db/db mice [11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30]. On day 15, the animals’ eyes were instilled with a drop of citicoline or vehicle approximately one hour prior to necropsy.…”

Section: Methodssupporting

confidence: 54%

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Effects of Liposomal Formulation of Citicoline in Experimental Diabetes-Induced Retinal Neurodegeneration

Bogdanov

Sampedro

Solà-Adell

et al. 2018

IJMS

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Diabetic retinopathy (DR) has been classically considered a microcirculatory disease of the retina. However, there is growing evidence to suggest that retinal neurodegeneration is also an early event in the pathogenesis of DR. Citicoline has been successfully used as a neuroprotective agent in the treatment of glaucoma but their effects on DR remain to be elucidated. On this basis, the main aim of the present study was to evaluate the effect of topical administration of citicoline in liposomal formulation on retinal neurodegeneration in db/db mouse and to investigate the underlying mechanisms of action. The treatment (citicoline or vehicle) was topically administered twice daily for 15 days. Retinal analyses were performed in vivo by electroretinography and ex vivo by using Western blot and immunofluorescence measurements. We found that the liposomal formulation of citicoline prevented glial activation and neural apoptosis in the diabetic retina. The main mechanism implicated in these beneficial effects were the inhibition of the downregulation of synaptophysin and its anti-inflammatory properties by means of preventing the upregulation of NF-κB and TNF-α (Tumor Necrosis Factor α) induced by diabetes. Overall, these results suggest that topical administration of citicoline in liposomal formulation could be considered as a new strategy for treating the early stages of DR.

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Section: Methodssupporting

confidence: 54%

“…Citicoline, by either injectable, oral or eye drop administration, has been used as a neuroprotective agent in the treatment of glaucoma [18,19,20,21,22]. However, the effect on DR has been barely analyzed and the underlying mechanism remains to be elucidated [23].…”

Section: Introductionmentioning

confidence: 99%

Effects of Liposomal Formulation of Citicoline in Experimental Diabetes-Induced Retinal Neurodegeneration

Bogdanov

Sampedro

Solà-Adell

et al. 2018

IJMS

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“…The choline deficiency could also be found in NAION patients, causing a deficiency of LysoPCs as products of choline; however, no significant differences of this molecule between patients and controls were found. Treatment with a precursor of choline, such as citicoline, has been used to improve consciousness levels in cerebral trauma and visual acuity in amblyopic patients (Fresina et al 2008) as well as to induce an improvement of the retinal and the visual pathway function in patients with glaucoma (Ottobelli et al 2013), although there are some controversial studies with regard to its efficiency (Davalos et al 2012;Parisi et al 2008).…”

Section: Metabolites As Potential Naion Biomarkersmentioning

confidence: 99%

Metabolomics in non-arteritic anterior ischemic optic neuropathy patients by liquid chromatography–quadrupole time-of-flight mass spectrometry

et al. 2014

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Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION) is a rare ischemic disease that affects the optic nerve. Pathophysiology and mechanism of ischemia of NAION remain uncertain, so the aim of this work is to establish the first metabolic fingerprinting of patients with NAION to discover possible new biomarkers. Twenty-four patients, aged 39-85 years, diagnosed with NAION, after a sudden loss of vision, were recruited for the study. Plasma samples of patients and controls were fingerprinted with liquid chromatography coupled to quadrupole time-offlight by electrospray ionization, and obtained data were filtered, aligned and statistically analysed to identify new biomarkers. The identity of compounds that were found to be significant in class separation was later confirmed by obtaining the characteristic MS/MS spectra and online databases. In general, biochemical and metabolic profiles between patients and controls did not show profound differences, but NAION patients presented disturbances in the phospholipid composition which lead to reduced plasma values of LysoPCs. Altered levels of other metabolites, such as L-Palmitoylcarnitine, have been detected and could be considered as potential biomarkers.

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“…In glaucoma patients, oral or intramuscular administration of citicoline was associated with an improved retinal and visual pathway functions [4–6]. Moreover, in patients with progressive glaucoma, oral citicoline was recently found to slow down glaucomatous rates of progression [7]. …”

Section: Introductionmentioning

confidence: 99%

Neuroprotective Effects of Citicoline in in Vitro Models of Retinal Neurodegeneration

Matteucci

Varano

Gaddini

et al. 2014

IJMS

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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.

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Citicoline Oral Solution in Glaucoma: Is There a Role in Slowing Disease Progression?

Cited by 69 publications

References 30 publications

Effects of Liposomal Formulation of Citicoline in Experimental Diabetes-Induced Retinal Neurodegeneration

Effects of Liposomal Formulation of Citicoline in Experimental Diabetes-Induced Retinal Neurodegeneration

Metabolomics in non-arteritic anterior ischemic optic neuropathy patients by liquid chromatography–quadrupole time-of-flight mass spectrometry

Neuroprotective Effects of Citicoline in in Vitro Models of Retinal Neurodegeneration

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