July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Citicoline ameliorates the effect of elevated intraocular pressure on functional connectivity in the visual pathway
Author Affiliations & Notes
  • Kevin C Chan
    NYU Langone Eye Center, Department of Ophthalmology, NYU School of Medicine, New York University, New York, New York, United States
    Department of Radiology, NYU School of Medicine, New York University, New York, New York, United States
  • Yolandi van der Merwe
    Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
    Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Matthew C. Murphy
    Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
    Department of Radiology, Mayo Clinic, Rochester, Minnesota, United States
  • Leon C. Ho
    Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Xiaoling Yang
    Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Yu Yu
    Department of Chemical and Biological Engineering, Hong Kong University of Science and Technology, Hong Kong, Hong Kong
  • Ying Chau
    Department of Chemical and Biological Engineering, Hong Kong University of Science and Technology, Hong Kong, Hong Kong
  • Christopher Kai-Shun Leung
    Hong Kong Eye Hospital, University Eye Center, Hong Kong, Hong Kong
    Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Hong Kong, Hong Kong
  • Gadi Wollstein
    NYU Langone Eye Center, Department of Ophthalmology, NYU School of Medicine, New York University, New York, New York, United States
  • Joel S Schuman
    NYU Langone Eye Center, Department of Ophthalmology, NYU School of Medicine, New York University, New York, New York, United States
  • Footnotes
    Commercial Relationships   Kevin Chan, None; Yolandi van der Merwe, None; Matthew Murphy, None; Leon Ho, None; Xiaoling Yang, None; Yu Yu, None; Ying Chau, None; Christopher Leung, None; Gadi Wollstein, None; Joel Schuman, Zeiss, Inc (P)
  • Footnotes
    Support  This work was supported in part by the National Institutes of Health R01-EY028125 (Bethesda, Maryland), and BrightFocus Foundation G2013077 and G2016030 (Clarksburg, Maryland).
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 6115. doi:
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      Kevin C Chan, Yolandi van der Merwe, Matthew C. Murphy, Leon C. Ho, Xiaoling Yang, Yu Yu, Ying Chau, Christopher Kai-Shun Leung, Gadi Wollstein, Joel S Schuman; Citicoline ameliorates the effect of elevated intraocular pressure on functional connectivity in the visual pathway. Invest. Ophthalmol. Vis. Sci. 2018;59(9):6115.

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

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Abstract

Purpose : Currently, lowering intraocular pressure (IOP) is the only clinically proven way to treat glaucoma. However, glaucomatous neurodegeneration may still continue after IOP is reduced. Recent studies suggest that citicoline may improve visual outcomes in glaucoma patients, yet its underlying mechanisms remain poorly understood. Here we examined the effects of IOP elevation on visuomotor response and brain functional connectivity (FC) with and without citicoline treatment.

Methods : Eighty-two Long Evans rats were divided into 6 groups and received acute or chronic IOP elevation to the right eye. Acute IOP elevation was induced by anterior chamber perfusion for 60min at 15mmHg (sham, n=10), 40mmHg (mild, n=12) or 130mmHg (severe, n=12). Chronic IOP elevation was induced by intracameral injection of an optically clear crosslinking hydrogel. A subset of animals (treated, n=19) received daily oral citicoline treatment (500mg/kg) for 7 days prior to, and every 48 hours for 14 days after gel injection, while another 19 rats were not treated orally (untreated). Ten rats received intracameral injection of buffer solution as sham control. IOP and visual acuity (VA) were measured by tonometry and optokinetics, respectively, for 5 weeks. Resting-state FC MRI was acquired at 9.4 Tesla covering the visual brain nuclei at 5 weeks after IOP elevation induction.

Results : Hydrogel injection significantly increased IOP for 5 weeks, with no difference between citicoline-treated (25.8±0.4mmHg) and untreated (26.4±0.5mmHg) groups (p>0.05). Severe acute IOP elevation resulted in lower VA [0.21±0.03cycles/degree (c/d)] than mild acute IOP elevation (0.38±0.03c/d) at week 5 (p<0.05), whereas VA of the citicoline-treated chronic group (0.31±0.01c/d) was higher than the untreated group (0.26±0.01c/d) (p<0.05). Larger magnitude of acute IOP elevation caused larger FC differences in subcortical visual nuclei (Fig. 1). In the chronic IOP elevation groups, untreated animals showed significantly decreased cortico-collicular, cortico-geniculate and subcortical FC, while citicoline treatment appeared to preserve or improve such FC (Fig. 2).

Conclusions : Increasing magnitude and duration of IOP elevation caused differential effects on visuomotor behavior and functional brain integrity, whereas citicoline ameliorated the effects. These findings merit further investigation into treating glaucoma beyond lowering IOP.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

 

 

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