In vivo evaluation of white matter integrity and anterograde transport in visual system after excitotoxic retinal injury with multimodal MRI and OCT

Leon C. Ho, Bo Wang, Ian P. Conner, Yolandi van der Merwe, Richard A. Bilonick, Seong Gi Kim, Ed X. Wu, Ian A. Sigal, Gadi Wollstein, Joel S. Schuman, Kevin C. Chan

Research output: Contribution to journalArticlepeer-review


Purpose. Excitotoxicity has been linked to the pathogenesis of ocular diseases and injuries and may involve early degeneration of both anterior and posterior visual pathways. However, their spatiotemporal relationships remain unclear. We hypothesized that the effects of excitotoxic retinal injury (ERI) on the visual system can be revealed in vivo by diffusion tensor magnetic resonance imagining (DTI), manganese-enhanced magnetic resonance imagining (MRI), and optical coherence tomography (OCT). Methods. Diffusion tensor MRI was performed at 9.4 Tesla to monitor white matter integrity changes after unilateral N-methyl-D-aspartate (NMDA)-induced ERI in six Sprague-Dawley rats and six C57BL/6J mice. Additionally, four rats and four mice were intravitreally injected with saline to compare with NMDA-injected animals. Optical coherence tomography of the retina and manganese-enhanced MRI of anterograde transport were evaluated and correlated with DTI parameters. Results. In the rat optic nerve, the largest axial diffusivity decrease and radial diffusivity increase occurred within the first 3 and 7 days post ERI, respectively, suggestive of early axonal degeneration and delayed demyelination. The optic tract showed smaller directional diffusivity changes and weaker DTI correlations with retinal thickness compared with optic nerve, indicative of anterograde degeneration. The splenium of corpus callosum was also reorganized at 4 weeks post ERI. The DTI profiles appeared comparable between rat and mouse models. Furthermore, the NMDA-injured visual pathway showed reduced anterograde manganese transport, which correlated with diffusivity changes along but not perpendicular to optic nerve. Conclusions. Diffusion tensor MRI, manganese-enhanced MRI, and OCT provided an in vivo model system for characterizing the spatiotemporal changes in white matter integrity, the eye–brain relationships and structural–physiological relationships in the visual system after ERI.

Original languageEnglish (US)
Pages (from-to)3788-3800
Number of pages13
JournalInvestigative Ophthalmology and Visual Science
Issue number6
StatePublished - 2015


  • Corpus callosum
  • Glutamate excitotoxicity
  • Magnetic resonance imaging
  • Optic neuropathy
  • Optical coherence tomography

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience


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