Journal
AGING-US
Volume 12, Issue 10, Pages 9031-9040Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/aging.103164
Keywords
Citicoline; age-related macular degeneration (AMD); neuroprotection; RPE; mitochondria
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Funding
- Arnold and Mabel Beckman Foundation
- Discovery Eye Foundation
- Polly and Michael Smith
- Edith and Roy Carver
- Iris and B. Gerald Cantor Foundation
- Unrestricted Departmental Grant from Research to Prevent Blindness
- NEI [R01 EY0127363]
- UCI School of Medicine
- Institute for Clinical and Translational Science (ICTS) at University of California Irvine
- 2017 Genentech/ARVO AMD Translational Research Fellowship
- 2016 RPB pilot research grant
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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.
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