Citicoline Modulates Glaucomatous Neurodegeneration Through Intraocular Pressure-Independent Control.

Autor: van der Merwe Y; UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, University of Pittsburgh, Pittsburgh, PA, USA.; Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA, USA., Murphy MC; UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, University of Pittsburgh, Pittsburgh, PA, USA.; Department of Radiology, Mayo Clinic, Rochester, MN, USA., Sims JR; Department of Ophthalmology, NYU Grossman School of Medicine, NYU Langone Health, New York University, New York, NY, USA., Faiq MA; Department of Ophthalmology, NYU Grossman School of Medicine, NYU Langone Health, New York University, New York, NY, USA., Yang XL; UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, University of Pittsburgh, Pittsburgh, PA, USA., Ho LC; UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, University of Pittsburgh, Pittsburgh, PA, USA., Conner IP; UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, University of Pittsburgh, Pittsburgh, PA, USA.; Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA, USA., Yu Y; Pleryon Therapeutics Limited, Shenzhen, China., Leung CK; University Eye Center, Hong Kong Eye Hospital, Hong Kong, China.; Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, China., Wollstein G; Department of Ophthalmology, NYU Grossman School of Medicine, NYU Langone Health, New York University, New York, NY, USA.; Center for Neural Science, College of Arts and Science, New York University, New York, NY, USA., Schuman JS; Department of Ophthalmology, NYU Grossman School of Medicine, NYU Langone Health, New York University, New York, NY, USA.; Center for Neural Science, College of Arts and Science, New York University, New York, NY, USA.; Neuroscience Institute, NYU Grossman School of Medicine, NYU Langone Health, New York University, New York, NY, USA., Chan KC; UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, University of Pittsburgh, Pittsburgh, PA, USA. chuenwing.chan@fulbrightmail.org.; Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA, USA. chuenwing.chan@fulbrightmail.org.; Department of Ophthalmology, NYU Grossman School of Medicine, NYU Langone Health, New York University, New York, NY, USA. chuenwing.chan@fulbrightmail.org.; Center for Neural Science, College of Arts and Science, New York University, New York, NY, USA. chuenwing.chan@fulbrightmail.org.; Department of Radiology, NYU Grossman School of Medicine, NYU Langone Health, New York University, New York, NY, USA. chuenwing.chan@fulbrightmail.org.; Neuroscience Institute, NYU Grossman School of Medicine, NYU Langone Health, New York University, New York, NY, USA. chuenwing.chan@fulbrightmail.org.
Jazyk: angličtina
Zdroj: Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics [Neurotherapeutics] 2021 Apr; Vol. 18 (2), pp. 1339-1359. Date of Electronic Publication: 2021 Apr 13.
DOI: 10.1007/s13311-021-01033-6
Abstrakt: Glaucoma is a neurodegenerative disease that causes progressive, irreversible vision loss. Currently, intraocular pressure (IOP) is the only modifiable risk factor for glaucoma. However, glaucomatous degeneration may continue despite adequate IOP control. Therefore, there exists a need for treatment that protects the visual system, independent of IOP. This study sought, first, to longitudinally examine the neurobehavioral effects of different magnitudes and durations of IOP elevation using multi-parametric magnetic resonance imaging (MRI), optokinetics and histology; and, second, to evaluate the effects of oral citicoline treatment as a neurotherapeutic in experimental glaucoma. Eighty-two adult Long Evans rats were divided into six groups: acute (mild or severe) IOP elevation, chronic (citicoline-treated or untreated) IOP elevation, and sham (acute or chronic) controls. We found that increasing magnitudes and durations of IOP elevation differentially altered structural and functional brain connectivity and visuomotor behavior, as indicated by decreases in fractional anisotropy in diffusion tensor MRI, magnetization transfer ratios in magnetization transfer MRI, T1-weighted MRI enhancement of anterograde manganese transport, resting-state functional connectivity, visual acuity, and neurofilament and myelin staining along the visual pathway. Furthermore, 3 weeks of oral citicoline treatment in the setting of chronic IOP elevation significantly reduced visual brain integrity loss and visual acuity decline without altering IOP. Such effects sustained after treatment was discontinued for another 3 weeks. These results not only illuminate the close interplay between eye, brain, and behavior in glaucomatous neurodegeneration, but also support a role for citicoline in protecting neural tissues and visual function in glaucoma beyond IOP control.
(© 2021. The American Society for Experimental NeuroTherapeutics, Inc.)
Databáze: MEDLINE
Externí odkaz: