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Yolandi van der Merwe, Leon Ho, Xiao-Ling Yang, Michael Steketee, Ian Conner, Seong-Gi Kim, Gadi Wollstein, Joel S Schuman, Kevin C Chan; Acute intraocular pressure elevation compromises optic nerve integrity and visuomotor behavior without apparent change in axonal transport. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):649.
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© ARVO (1962-2015); The Authors (2016-present)
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.
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.
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.
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.
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