June 2015
Volume 56, Issue 7
Free
ARVO Annual Meeting Abstract  |   June 2015
Longitudinal Profiles of Intraocular Pressure, Ocular Morphology and Visual Pathway Integrity in DBA/2J and C57BL/6J Mice
Author Affiliations & Notes
  • Xiaoling Yang
    Neuroimaging Laboratory, University of Pittsburgh, Pittsburgh, PA
    UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, PA
  • Leon Ho
    Neuroimaging Laboratory, University of Pittsburgh, Pittsburgh, PA
    Department of Electrical and Electronic Engineering, The University of Hong Kong, Hong Kong, China
  • Yolandi van der Merwe
    Neuroimaging Laboratory, University of Pittsburgh, Pittsburgh, PA
    Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA
  • Ian Conner
    UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, PA
    Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA
  • Seong-Gi Kim
    Neuroimaging Laboratory, University of Pittsburgh, Pittsburgh, PA
    Center for Neuroscience Imaging Research, Institute for Basic Science, Departments of Biomedical Engineering and Biological Sciences, Sungkyunkwan University, Suwon, Korea (the Republic of)
  • Gadi Wollstein
    UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, PA
    Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA
  • Joel S Schuman
    UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, PA
    Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA
  • Kevin C Chan
    Neuroimaging Laboratory, University of Pittsburgh, Pittsburgh, PA
    UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, School of Medicine, University of Pittsburgh, Pittsburgh, PA
  • Footnotes
    Commercial Relationships Xiaoling Yang, None; Leon Ho, None; Yolandi van der Merwe, None; Ian Conner, None; Seong-Gi Kim, None; Gadi Wollstein, None; Joel Schuman, Zeiss, Inc. (P); Kevin Chan, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2015, Vol.56, 3984. doi:
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    • Get Citation

      Xiaoling Yang, Leon Ho, Yolandi van der Merwe, Ian Conner, Seong-Gi Kim, Gadi Wollstein, Joel S Schuman, Kevin C Chan; Longitudinal Profiles of Intraocular Pressure, Ocular Morphology and Visual Pathway Integrity in DBA/2J and C57BL/6J Mice. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3984.

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

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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.  

 

 
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