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Article: Citicoline Modulates Glaucomatous Neurodegeneration Through Intraocular Pressure-Independent Control

TitleCiticoline Modulates Glaucomatous Neurodegeneration Through Intraocular Pressure-Independent Control
Authors
KeywordsCiticoline
Intraocular pressure
Magnetic resonance imaging
Optokinetics
Visual system
Glaucoma
Issue Date2021
PublisherSpringer New York LLC. The Journal's web site is located at https://www.springer.com/journal/13311
Citation
Neurotherapeutics, 2021, v. 18 n. 2, p. 1339-1359 How to Cite?
AbstractGlaucoma 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.
Persistent Identifierhttp://hdl.handle.net/10722/306633
ISSN
2021 Impact Factor: 6.088
2020 SCImago Journal Rankings: 2.496
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorvan der Merwe, Y-
dc.contributor.authorMurphy, MC-
dc.contributor.authorSims, JR-
dc.contributor.authorFaiq, MA-
dc.contributor.authorYang, XL-
dc.contributor.authorHo, LC-
dc.contributor.authorConner, IP-
dc.contributor.authorYu, Y-
dc.contributor.authorLeung, CK-
dc.contributor.authorWollstein, G-
dc.contributor.authorSchuman, JS-
dc.contributor.authorChan, KC-
dc.date.accessioned2021-10-22T07:37:24Z-
dc.date.available2021-10-22T07:37:24Z-
dc.date.issued2021-
dc.identifier.citationNeurotherapeutics, 2021, v. 18 n. 2, p. 1339-1359-
dc.identifier.issn1933-7213-
dc.identifier.urihttp://hdl.handle.net/10722/306633-
dc.description.abstractGlaucoma 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.-
dc.languageeng-
dc.publisherSpringer New York LLC. The Journal's web site is located at https://www.springer.com/journal/13311-
dc.relation.ispartofNeurotherapeutics-
dc.rightsThis is a post-peer-review, pre-copyedit version of an article published in [insert journal title]. The final authenticated version is available online at: https://doi.org/[insert DOI]-
dc.subjectCiticoline-
dc.subjectIntraocular pressure-
dc.subjectMagnetic resonance imaging-
dc.subjectOptokinetics-
dc.subjectVisual system-
dc.subjectGlaucoma-
dc.titleCiticoline Modulates Glaucomatous Neurodegeneration Through Intraocular Pressure-Independent Control-
dc.typeArticle-
dc.identifier.emailLeung, CK: cleung21@hku.hk-
dc.identifier.authorityLeung, CK=rp02798-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1007/s13311-021-01033-6-
dc.identifier.pmid33846961-
dc.identifier.pmcidPMC8423893-
dc.identifier.scopuseid_2-s2.0-85104404100-
dc.identifier.hkuros328568-
dc.identifier.volume18-
dc.identifier.issue2-
dc.identifier.spage1339-
dc.identifier.epage1359-
dc.identifier.isiWOS:000639643500001-
dc.publisher.placeUnited States-

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