Acute intraocular pressure elevation compromises optic nerve integrity and visuomotor behavior without apparent change in axonal transport

Abstract

 

Purpose

 

Ocular hypertension is often present in glaucoma and retinal ischemia, however the pathophysiological events associated with different extents of intraocular (IOP) elevation are not fully understood. Here we used MRI and optokinetics to longitudinally monitor the optic nerve integrity and visuomotor behavior after acute IOP elevation to two levels.

 

Methods

 

Sixteen Long Evans rats received unilateral IOP elevation in the right eye at 40mmHg (mild; n=9) or 90mmHg (severe; n=7) for 60 min via physiological saline anterior chamber perfusion. The left eye was untreated and served as an internal control. Diffusion tensor MRI (DTI) was performed at day 3, and week 1, 2 and 5 using a 9.4 Tesla scanner. Visuomotor behavior was quantified at week 1, 2 and 5 with an OptoMotry virtual-reality optokinetic system. After DTI at week 5, manganese-enhanced MRI was performed before and 8 hours after bilateral intravitreal MnCl₂ injection. DTI-derived parameters [fractional anisotropy (FA), axial diffusivity (λ_//) and radial diffusivity (λ_┴)] and Mn enhancement were measured in the prechiasmatic optic nerve, compared bilaterally and correlated with visuomotor function.

 

Results

 

After mild and severe IOP elevation, DTI at day 3 to week 5 showed significantly lower FA in the right optic nerve by 5%-10% and 8%-12% respectively compared to the uninjured left optic nerve (Fig. 1). Significantly higher λ_┴ was also found in the right optic nerve by 12%-16% and 16%-31% respectively at day 3 to week 5 after mild and severe IOP elevation. For visuomotor behavior, severe IOP elevation led to significantly worse visual acuity (VA) deterioration than mild IOP elevation throughout the experimental period. Significant positive and negative correlations were also observed between VA and FA and between VA and λ_┴ in the optic nerve respectively throughout the experimental period. No significant difference in λ_// or Mn enhancement was observed between bilateral optic nerves.

 

Conclusions

 

Acute IOP elevation at 40 and 90mmHg for 60 min led to significant changes in FA and λ_┴ in the optic nerve at day 3 to week 5. λ_// or Mn anterograde transport did not differ between injured and uninjured optic nerves, suggestive of relatively preserved axonal integrity over time. The longitudinal structural integrity, as reflected by changes in FA and λ_┴, corresponded with changes in visuomotor function.