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Role of Citicoline in an in vitro AMD model.

ABSTRACT: Citicoline is the exogenous form of the nootropic, Cytidine 5'-diphosphate-choline that exerts its neuroprotective effects in the brain as well as in the eye. The current study characterized the cytoprotective effects of purified Citicoline in transmitochondrial AMD (Age-related Macular Degeneration) RPE cybrid cells which carry diseased mitochondria from clinically characterized AMD patients. The effects of Citicoline were examined via flow cytometry analysis of AnnexinV/ PI-stained cells, IncuCyte live-cell imaging analysis to quantify cells undergoing caspase-3/7-mediated apoptosis, analyses of gene expression profiles of apoptosis, hypoxia, and angiogenesis markers, and measurement of ROS levels and cell viability. Our results demonstrated that Citicoline when added exogenously alleviates apoptotic effects as evidenced by diminished AnnexinV/PI and Caspase-3/7 staining, downregulation of apoptosis genes, enhanced cell viability, and reduced oxidative stress in AMD RPE cybrid cells. In conclusion, our study identified Citicoline as a protector in AMD RPE cybrid cells in vitro. However, further studies are required to establish the merit of Citicoline as a cytoprotective molecule in AMD and to decipher the molecular underpinnings of its mechanism of action in AMD.

SUBMITTER: Nashine S

PROVIDER: S-EPMC7288938 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Role of Citicoline in an <i>in vitro</i> AMD model.

Nashine Sonali S Kenney M Cristina MC

Aging 20200529 10

Citicoline is the exogenous form of the nootropic, Cytidine 5'-diphosphate-choline that exerts its neuroprotective effects in the brain as well as in the eye. The current study characterized the cytoprotective effects of purified Citicoline in transmitochondrial AMD (Age-related Macular Degeneration) RPE cybrid cells which carry diseased mitochondria from clinically characterized AMD patients. The effects of Citicoline were examined via flow cytometry analysis of AnnexinV/ PI-stained cells, Incu ...[more]

PMID: 32470946

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Project description:PURPOSE:To evaluate the presence and concentration of citicoline and its metabolites (choline, cytidine and uridine) in the vitreous body in human eyes after topical application of an ophthalmic solution of citicoline 2%, in vivo. METHODS:Twenty-one subjects affected by epiretinal membrane with surgical indication for pars-plana vitrectomy underwent treatment with 1 drop 3 times/day of a solution of citicoline 2%, 0.2% high molecular weight hyaluronic acid and 0.01% benzalkonium chloride (OMK1, Omikron Italia s.r.l., Rome, Italy) 14 days before surgery and 2 hours prior to surgery. Five additional patients served as controls and received an OMK1 vehicle solution without citicoline. The vitreous samples were taken at the beginning of the pars-plana vitrectomy and analyzed for qualitative/quantitative determination of vitreous concentration of citicoline and its metabolites by means of high performance liquid chromatography. RESULTS:The overall mean concentration of citicoline in patients treated with citicoline 2% solution was 406.72 ± 52.99 ?g/mL, while the mean concentration of choline, cytidine and uridine was 180.88 ± 41.49 ?g/mL, 44.45 ± 10.19 ?g/mL and 330.41 ± 75.8 ?g/mL, respectively. The concentration of citicoline in phakic eyes (n = 13, 366.61 ± 129.61 ?g/mL) was lower compared to that found in pseudophakic eyes (n = 8, 435.89 ± 131.42 ?g/mL) and the difference was not statistically significant. The concentration of citicoline in the control eyes was 45.66 ± 26.36 ?g/mL, while the concentration of choline, cytidine and uridine were 17.21 ± 9.93 ?g/mL, 6.24 ± 3.6 ?g/mL and 172.80 ± 99.76 ?g/mL, respectively. CONCLUSION:Citicoline can reach the human vitreous in high concentration when administered in ophthalmic solution. This evidence contributes to the build-up of the pyramid of the evidences required for determining the role of citicoline administered in ophthalmic formulation in retinal and optic nerve neurodegenerative diseases.

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Role of Citicoline in an in vitro AMD model.

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Role of Citicoline in an <i>in vitro</i> AMD model.

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