July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
Non-invasive Detection of Visual Pathway Abnormalities in Genetic Experimental Models of Glaucoma Using Diffusion Tensor MRI
Author Affiliations & Notes
  • Max Colbert
    Ophthalmology, New York University School of Medicine, New York, New York, United States
  • Yolandi van der Merwe
    Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Leon C. Ho
    Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Gillian J McLellan
    Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, Madison, Wisconsin, United States
    McPherson Eye Research Institute, University of Wisconsin-Madison, Madison, Wisconsin, United States
  • Samuel A. Hurley
    Department of Radiology, University of Wisconsin-Madison, Madison, Wisconsin, United States
  • John H Fingert
    Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, Iowa, United States
  • Carlos Parra
    Ophthalmology, New York University School of Medicine, New York, New York, United States
  • Muneeb A. Faiq
    Ophthalmology, New York University School of Medicine, New York, New York, United States
  • Gadi Wollstein
    Ophthalmology, New York University School of Medicine, New York, New York, United States
  • Joel Schuman
    Ophthalmology, New York University School of Medicine, New York, New York, United States
  • Kevin C Chan
    Ophthalmology, New York University School of Medicine, New York, New York, United States
    Department of Radiology, New York University School of Medicine, New York, New York, United States
  • Footnotes
    Commercial Relationships   Max Colbert, None; Yolandi van der Merwe, None; Leon Ho, None; Gillian McLellan, None; Samuel Hurley, None; John Fingert, None; Carlos Parra, None; Muneeb Faiq, None; Gadi Wollstein, None; Joel Schuman, Zeiss, Inc. (P); Kevin Chan, None
  • Footnotes
    Support  NIH Grants RO1EY028125, K08EY018609, P30EY0016665, UL1TR000427; BrightFocus Foundation G2013077 and G2016030; Research to Prevent Blindness/Stavros Niarchos Foundation International Research Collaborators Award; and unrestricted funds to the Department of Ophthalmology and Visual Science, University of Wisconsin-Madison from Research to Prevent Blindness.
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 4823. doi:https://doi.org/
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      Max Colbert, Yolandi van der Merwe, Leon C. Ho, Gillian J McLellan, Samuel A. Hurley, John H Fingert, Carlos Parra, Muneeb A. Faiq, Gadi Wollstein, Joel Schuman, Kevin C Chan; Non-invasive Detection of Visual Pathway Abnormalities in Genetic Experimental Models of Glaucoma Using Diffusion Tensor MRI. Invest. Ophthalmol. Vis. Sci. 2019;60(9):4823. doi: https://doi.org/.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose : Although recent studies in humans and animal models suggest the involvement of the brain's visual system in glaucoma, its extents across different etiopathogeneses are not completely understood. In this study, we used non-invasive diffusion tensor MRI (DTI) to evaluate the visual pathway in 3 genetic animal models of glaucoma.

Methods : Three genetically determined glaucoma models and their controls were employed: (1) LTBP2 feline model of primary congenital glaucoma (n=3) and age-matched normal cats (n=3) at 2-4 years old; (2) DBA/2J mouse model of hereditary pigmentary glaucoma (n=8) and its genetically-matched DBA/2J-Gpnmb+ control strain (n=7) at 7, 9 and 12 months old; and (3) TBK1 transgenic mouse model of normal tension glaucoma (n=4) and its wild-type littermates (n=4) at about 20 months old. Cat DTI was performed using a 3-Tesla GE MRI scanner, whereas mouse DTI was performed using a 9.4-Tesla Agilent MRI scanner. DTI parameters including fractional anisotropy (FA), axial diffusivity (λ//) and radial diffusivity (λ) were evaluated along the optic nerves, optic tracts and/or internal capsules, and compared between groups using ANOVA and post-hoc multiple comparisons correction tests.

Results : LTBP2 mutant cats with glaucoma had significantly lower FA and higher λ in the optic tracts when compared to the normotensive, age-matched controls, while λ// exhibited no difference (Figure 1). When compared to the normotensive DBA/2J-Gpnmb+ controls, the DBA/2J mice exhibited significantly lower FA and λ//, and higher λ along the visual pathway (Figure 2) in concurrence with increasing intraocular pressure (IOP) at 7-12 months old. No apparent DTI difference was observed between transgenic TBK1 mice and wild-type littermates along the visual pathway (not shown).

Conclusions : While LTBP2 cats and DBA/2J mice are characterized by significant IOP elevation and retinal ganglion cell (RGC) loss, TBK1 mice have been found to exhibit no apparent IOP change and less RGC loss even in older ages. The current DTI results suggest that animals with LTBP2 mutation or DBA/2J melanosomal protein mutation had compromised structural integrity in the central visual pathway. Future studies will examine the relationships between IOP, RGC loss, visual pathway integrity, and their functional relevance in different forms and stages of glaucoma.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

 

 

×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×