Citicoline in Ophthalmological Neurodegenerative Disease: A Comprehensive Review

Oddone, Francesco; Rossetti, Luca; Parravano, Mariacristina; Sbardella, Diego; Coletta, Massimo; Ziccardi, Lucia; Roberti, Gloria; Carnevale, Carmela; Romano, Dario; Manni, Gianluca; Parisi, Vincenzo

doi:10.3390/ph14030281

Cited by 19 publications

(21 citation statements)

References 119 publications

(80 reference statements)

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“…The treatment with LG saves a significant portion of these RGCs, and this is particularly relevant in peripheral retina, where LG treatment results in virtually complete rescue of the RGCs. According to these observations, both preclinical and clinical studies have reported RGC loss and PERG defects in glaucomatous retinas, which were protected by antioxidant treatments obtained with nutritional supplements ( Parisi et al, 2014 ; Cammalleri et al, 2020 ; Himori et al, 2021 ; Oddone et al, 2021 ).…”

Section: Discussionmentioning

confidence: 94%

The Potential of Lisosan G as a Possible Treatment for Glaucoma

et al. 2021

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Lisosan G (LG), a fermented powder obtained from whole grains, is a nutritional supplement containing a variety of metabolites with documented antioxidant properties. We have recently demonstrated that orally administered LG protects diabetic rodent retinas from oxidative stress, inflammation, apoptosis, blood-retinal barrier disruption, and functional damage. Here, we investigated whether LG may exert protective effects in a model of glaucoma and measured the amounts of selected LG components that reach the retina after oral LG administration. Six-month-old DBA/2J mice were given an aqueous LG solution in place of drinking water for 2 mo. During the 2 mo of treatment with LG, the intraocular pressure (IOP) was monitored and the retinal ganglion cell (RGC) functional activity was recorded with pattern-electroretinography (PERG). At the end of the 2-mo period, the expression of oxidative stress and inflammatory markers was measured with qPCR, and RGC survival or macroglial activation were assessed with immunofluorescence. Alternatively, LG was administered by gavage and the concentrations of four of the main LG components (nicotinamide, gallic acid, 4-hydroxybenzoic acid, and quercetin) were measured in the retinas in the following 24 h using mass spectrometry. LG treatment in DBA/2J mice did not influence IOP, but it affected RGC function since PERG amplitude was increased and PERG latency was decreased with respect to untreated DBA/2J mice. This improvement of RGC function was concomitant with a significant decrease of both oxidative stress and inflammation marker expression, of RGC loss, and of macroglial activation. All four LG metabolites were found in the retina, although with different proportions with respect to the amount in the dose of administered LG, and with different temporal profiles in the 24 h following administration. These findings are consistent with neuroenhancing and neuroprotective effects of LG in glaucoma that are likely to derive from its powerful antioxidant properties. The co-occurrence of different metabolites in LG may provide an added value to their beneficial effects and indicate LG as a basis for the potential treatment of a variety of retinal pathologies.

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Section: Discussionmentioning

confidence: 94%

The Potential of Lisosan G as a Possible Treatment for Glaucoma

et al. 2021

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“…The effects of citicoline in diabetes appeared to be directed to a multitude of mechanisms, including glutamate excitotoxicity and oxidative stress modulation, increasing neurotrophin levels, improving the release of the neurotransmitters, enhancing the axonal transport and neuron homeostasis, promoting mitochondrial function, and modulating insulin signaling. Citicoline is involved in the sphingomyelin biosynthesis favoring the plasma membrane stabilization in the RGC axons [86,87].…”

Section: Topical Citicolinementioning

confidence: 99%

Understanding Neurodegeneration from a Clinical and Therapeutic Perspective in Early Diabetic Retinopathy

2022

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Recent evidence indicates that neurodegeneration is a critical element of diabetic retinopathy (DR) pathogenesis. The neuronal cells’ apoptosis contributes to microvascular impairment and blood–retinal barrier breakdown. Therefore, neurodegeneration represents an early intervention target to slow and prevent the development of microvascular alterations visible on clinical examination. Multimodal imaging features and functional assessment can permit the identification of neuronal damage in a subclinical stage before the recognition of DR signs. Clinical features of neurodegeneration are crucial in identifying patients at high risk of developing a vascular impairment and, thus, serve as outcome measures to understand the efficacy of supplementation. The optimal approach for targeting neurodegeneration contemplates the use of topical compounds that possibly act on different elements of the pathogenic cascade. To date, clinical trials available on humans tested three different topical agents, including brimonidine, somatostatin, and citicoline, with promising results.

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“…Cytidine 5′-diphosphocholine, better known as Citicoline, already finds its therapeutic use in systemic neurodegenerations, such as AD, PD and ischemia. In fact, citicoline, since its chemical structure resembles a precursor of phosphatidylcholine, has several action mechanisms, including phospholipid homeostasis, redox homeostasis, mitochondrial dynamics, cholinergic and dopaminergic neurotransmission [ 204 , 205 , 206 ]. Therefore, given the similarities between the neurodegeneration pattern of glaucoma and other neurodegenerative diseases (e.g., AD), citicoline has become increasingly used also in glaucoma studies showing its ability to stabilize the plasma membrane of RGC axons and to counteract glutamate excitotoxicity [ 207 ], as well as to control oxidative stress.…”

Section: Neuroprotectionmentioning

confidence: 99%

Risk Factors for Retinal Ganglion Cell Distress in Glaucoma and Neuroprotective Potential Intervention

Vernazza

Oddone

Tirendi

et al. 2021

IJMS

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Retinal ganglion cells (RGCs) are a population of neurons of the central nervous system (CNS) extending with their soma to the inner retina and with their axons to the optic nerve. Glaucoma represents a group of neurodegenerative diseases where the slow progressive death of RGCs results in a permanent loss of vision. To date, although Intra Ocular Pressure (IOP) is considered the main therapeutic target, the precise mechanisms by which RGCs die in glaucoma have not yet been clarified. In fact, Primary Open Angle Glaucoma (POAG), which is the most common glaucoma form, also occurs without elevated IOP. This present review provides a summary of some pathological conditions, i.e., axonal transport blockade, glutamate excitotoxicity and changes in pro-inflammatory cytokines along the RGC projection, all involved in the glaucoma cascade. Moreover, neuro-protective therapeutic approaches, which aim to improve RGC degeneration, have also been taken into consideration.

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Citicoline in Ophthalmological Neurodegenerative Disease: A Comprehensive Review

Cited by 19 publications

References 119 publications

The Potential of Lisosan G as a Possible Treatment for Glaucoma

The Potential of Lisosan G as a Possible Treatment for Glaucoma

Understanding Neurodegeneration from a Clinical and Therapeutic Perspective in Early Diabetic Retinopathy

Risk Factors for Retinal Ganglion Cell Distress in Glaucoma and Neuroprotective Potential Intervention

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