Longitudinal Profiles of Intraocular Pressure, Ocular Morphology and Visual Pathway Integrity in DBA/2J and C57BL/6J Mice

Abstract

 

Purpose

 

Although elevated intraocular pressure (IOP) and age are major risk factors for glaucoma, their effects on glaucoma pathogenesis are incompletely understood. This study evaluated longitudinally the IOP, ocular anatomy and structural integrity of the visual pathway in the DBA/2J (D2) mouse model of chronic glaucoma with an aim to probe the onset of glaucomatous changes and their progression. Age-matched C57BL/6J (B6) mice were assessed as a control.

 

Methods

 

Thirteen D2 and 6 B6 mice underwent anatomical T2-weighted imaging of the eye and diffusion tensor imaging (DTI) of the brain at 5, 7, 9 and 12 months old (mos, n=4 for B6 at 9 and 12 mos) with a 9.4 Tesla MRI scanner. The IOP of each eye was measured every 1-2 months using the TonoLab rebound tonometer. Visuomotor behavior was quantified at 12 mos using the OptoMotry virtual-reality optokinetic system.

 

Results

 

The IOP of D2 mice began to increase at 8-9 mos, peaked at 10 mos and remained significantly higher than baseline thereafter (Fig. 1a). A small but significant IOP increase was also observed in B6 mice at 9 mos onward. For ocular morphology (Fig. 1b), all 3 dimensions measured [anterior chamber depth (ACD), vitreous body depth (VBD) and axial length (AL)] began to increase in D2 at 9 mos. ACD and AL continued to increase at 12 mos. For visual pathway integrity (Fig. 2), DTI-derived parametric changes [fractional anisotropy (FA), axial diffusivity (λ_//) and radial diffusivity (λ_┴)] began at 9 mos in the optic nerve of D2 and progressed further at 12 mos. Smaller DTI changes were observed in the optic tract of D2 at 9 and 12 mos. A small but significant λ_// decrease was also observed in the optic nerve of B6 at 9 and 12 mos. Note also the lower FA and higher λ_┴ in the optic nerve and optic tract of D2 than B6 at 5 and 7 mos. For visuomotor behavior, the visual acuity of D2 (0.035±0.060 cycle/degree) was significantly worse than that of B6 (0.380±0.026 cycle/degree) at 12 mos (p<0.001).

 

Conclusions

 

The ocular dimensions and visual pathway integrity in D2 mice began to change at the onset of IOP increase at 8-9 mos and progressed further at 12 mos, resulting in deterioration in visuomotor function compared to B6 mice of the same age. The constant DTI differences in the visual pathway between D2 and B6 before IOP elevation might reflect early pathophysiological events that affected water diffusion such as gliosis.