Citicoline preserves optic nerve integrity and visuomotor function following chronic intraocular pressure elevation

Abstract

Purpose : Although lowering of intraocular pressure (IOP) is the only clinically proven glaucoma intervention in afflicted individuals, glaucomatous neurodegeneration and visual impairment may continue to progress in some patients following this treatment. Recent studies suggest the potential of citicoline, an intermediate in the generation of phosphatidylcholine from choline, to improve visual outcome in glaucoma patients, but its neuroprotective roles remain unclear. Here we examined the effects of oral citicoline treatment on white matter integrity and visuomotor response in a chronic IOP elevation animal model.

Methods : Twenty-five Long Evans rats were intracamerally injected in the right eye with an optically clear cross-linking hydrogel consisting of 6% vinysulfonated hyaluronic acid (HA) and 6% thiolated HA that obstructed aqueous outflow. Eleven of the rats received daily citicoline treatment (500mg/kg) via oral gavaging for 7 days prior to, and every 48 hours for 14 days after hydrogel injection. IOP and visual acuity (VA) were measured with a TonoLab tonometer and OptoMotry virtual reality system respectively before and for 5 weeks after hydrogel injection. Diffusion tensor imaging was performed using a 9.4 Tesla MRI scanner to measure white matter integrity indicated by fractional anisotropy (FA) in the prechiasmatic optic nerve (ON) at 5 weeks following hydrogel injection.

Results : Hydrogel injection significantly elevated IOP in the right eye for 5 weeks, with no pressure difference between citicoline treated and untreated animals (Fig. 1a). VA of left eye remained unchanged over time, whereas VA of right eye deteriorated starting at day 7, and was significantly worse in untreated animals compared to citicoline treated animals (Fig. 1b). The decrease in FA in the ON was significantly smaller for citicoline treated animals compared to untreated animals (Fig. 2a & 2b). In addition, FA in right ON was positively correlated with VA in right eye for all animals (Fig. 2c).

Conclusions : Chronic IOP elevation for up to 5 weeks caused significant changes in the visuomotor behavior and white matter integrity in the prechiasmatic optic nerve, whereas citicoline treatment ameliorated the effects. Our results appeared consistent with recent literature that suggests citicoline can act upon impaired white matter and improve functional outcomes in neurodegenerative diseases.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.