Neuroprotective Effects of Citicoline in in Vitro Models of Retinal Neurodegeneration

Abstract

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.

Management of Glaucoma As a Neurodegenerative Disease

“…It is also thought to play a role in increasing the metabolism of cerebral structures via facilitating the biosynthesis of phospholipids in neuronal membranes [54], and inhibiting phospholipid degradation [53]. In vitro studies have previously reported data supporting Citicoline's protective effects against apoptosis, and reducing synaptic loss in retinal cell cultures [55,56]. Due to these features, Citicoline has been shown to have a neuroprotective effect in conditions such as stroke [57,58] and PD [59].…”

Cytidine 5′-Diphosphocholine (Citicoline): Evidence for a Neuroprotective Role in Glaucoma

“…Specifically, in rodent retinal cultures and animal models of glaucoma, citicoline induced antiapoptotic effects in mitochondrial-dependent cell death, increased retinal levels of dopamine, counteracted retinal nerve fibers layer thinning, and promoted neurite regeneration (reviewed in Parisi et al, 2018 [52]). Furthermore, in vitro studies in retinal cells suggest that citicoline might have neuroprotective activity by blocking the excitotoxicity cascade leading to glutamate-mediated cell death [74,75] and decreasing both proapoptotic effects and synapse loss [76].…”

Efficacy of Neuroprotective Support of the Patients With Diabetes Mellitus During Panretinal Laser Photocoagulation

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