June 2020
Volume 61, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2020
Choline metabolism in the visual cortex following chronic intraocular pressure elevation and oral citicoline treatment
Author Affiliations & Notes
  • Jeffrey Ryan Sims
    Department of Ophthalmology, New York University School of Medicine, NYU Langone Health, New York, New York, United States
  • Yolandi van der Merwe
    UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Matthew C. Murphy
    Department of Radiology, Mayo Clinic, Rochester, Minnesota, United States
  • Xiaoling Yang
    UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Leon C. Ho
    UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Ian P Conner
    UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Yu Yu
    Pleryon Therapeutics Ltd., Shenzhen, China
  • Christopher Kai-Shun Leung
    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
  • Gadi Wollstein
    Department of Ophthalmology, New York University School of Medicine, NYU Langone Health, New York, New York, United States
  • Joel S Schuman
    Department of Ophthalmology, New York University School of Medicine, NYU Langone Health, New York, New York, United States
    Department of Biomedical Engineering, NYU Tandon School of Engineering, Brooklyn, New York, United States
  • Kevin C Chan
    Department of Ophthalmology, New York University School of Medicine, NYU Langone Health, New York, New York, United States
    Department of Radiology, New York University School of Medicine, NYU Langone Health, New York, New York, United States
  • Footnotes
    Commercial Relationships   Jeffrey Sims, None; Yolandi van der Merwe, None; Matthew Murphy, None; Xiaoling Yang, None; Leon Ho, None; Ian Conner, None; Yu Yu, Pleryon Therapeutics Limited (P); Christopher Leung, None; Gadi Wollstein, None; Joel Schuman, Zeiss, Inc (P); Kevin Chan, None
  • Footnotes
    Support  This work was supported in part by the National Institutes of Health R01-EY028125 (Bethesda, Maryland); BrightFocus Foundation G2013077. G2016030 and G20190103 (Clarksburg, Maryland); Research to Prevent Blindness/Stavros Niarchos Foundation International Research Collaborators Award (New York, New York); and an Unrestricted Grant from Research to Prevent Blindness to NYU Langone Health Department of Ophthalmology.
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 648. doi:
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    • Get Citation

      Jeffrey Ryan Sims, Yolandi van der Merwe, Matthew C. Murphy, Xiaoling Yang, Leon C. Ho, Ian P Conner, Yu Yu, Christopher Kai-Shun Leung, Gadi Wollstein, Joel S Schuman, Kevin C Chan; Choline metabolism in the visual cortex following chronic intraocular pressure elevation and oral citicoline treatment. Invest. Ophthalmol. Vis. Sci. 2020;61(7):648.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Recent studies suggest that glaucoma involves trans-neuronal changes in choline metabolism in the brain’s visual system. In addition, citicoline has been suggested as a potential therapeutic for neurodegenerative diseases including glaucoma, yet the underlying mechanisms remain unclear. Here, we use proton magnetic resonance spectroscopy (1H-MRS) and optokinetics to examine the effects of chronic intraocular pressure (IOP) elevation and oral citicoline treatment on brain metabolism and visual function in a novel rat model of experimental glaucoma.

Methods : Twenty-three adult Long Evans rats were divided into 3 groups. In Group 1 (n=6) and Group 2 (n=7), the right eye was intracamerally injected with an optically clear crosslinking hydrogel for chronic IOP elevation; Group 2 also received daily oral citicoline dosing for 7 days prior to hydrogel injection, and every 48 hours for 14 days post-injection. The sham group (Group 3, n=7) received an intracameral injection of buffer solution only. IOP and visual acuity (VA) were measured longitudinally using a TonoLab rebound tonometer and the OptoMotry virtual reality system, respectively. 1H-MRS was acquired over the left and right visual cortices at 5 weeks post-injection using a 9.4T MRI scanner.

Results : VA of the left, uninjured eyes remained constant over the experimental period, whereas VA of citicoline-treated right eyes appeared to deteriorate more slowly than untreated right eyes after similar levels of chronic IOP elevation (Fig 1). The left visual cortex projecting from the right, hydrogel-injected eye without citicoline treatment showed a reduced choline level compared to the contralateral right visual cortex projecting from the left, uninjured eye. Interestingly, a higher choline level was found in the left visual cortex of citicoline-treated rats compared to untreated rats (Fig 2). No apparent metabolic change was observed in the sham group.

Conclusions : Chronic IOP elevation by intracameral hydrogel injection significantly decreased visual acuity and choline-containing compounds in the visual cortex, whereas oral administration of citicoline ameliorated these effects. Our findings suggest that oral citicoline treatment may possess neuroprotective effects on the visual cortex by replenishing choline contents during glaucomatous degeneration, and 1H-MRS may help in monitoring such metabolic changes in the brain.

This is a 2020 ARVO Annual Meeting abstract.

 

 

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