September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Age-related changes in anterograde transport, axonal integrity and visuomotor function in DBA/2J and C57BL/6J mice
Author Affiliations & Notes
  • Xiaoling Yang
    NeuroImaging Laboratory, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
    UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Yolandi van der Merwe
    NeuroImaging Laboratory, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
    Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Leon C Ho
    NeuroImaging Laboratory, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
    Department of Electrical and Electronic Engineering, University of Hong Kong, Hong Kong, China
  • Ian P Conner
    UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
    Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Kira L Lathrop
    UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Gadi Wollstein
    UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
    Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Joel S Schuman
    UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
    Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Kevin C Chan
    NeuroImaging Laboratory, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
    UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Science Research Center, Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
  • Footnotes
    Commercial Relationships   Xiaoling Yang, None; Yolandi van der Merwe, None; Leon Ho, None; Ian Conner, None; Kira Lathrop, None; Gadi Wollstein, None; Joel Schuman, Zeiss Inc. (P); Kevin Chan, None
  • Footnotes
    Support  National Institutes of Health P30-EY008098 and UL1-TR000005 (Bethesda, Maryland); BrightFocus Foundation G2013077 (Clarksburg, Maryland), Alcon Research Institute Young Investigator Grant (Fort Worth, Texas); Eye and Ear Foundation (Pittsburgh, Pennsylvania); and Research to Prevent Blindness (New York, New York).
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 5144. doi:
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    • Get Citation

      Xiaoling Yang, Yolandi van der Merwe, Leon C Ho, Ian P Conner, Kira L Lathrop, Gadi Wollstein, Joel S Schuman, Kevin C Chan; Age-related changes in anterograde transport, axonal integrity and visuomotor function in DBA/2J and C57BL/6J mice. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5144.

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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 the IOP, visuomotor function, anterograde transport and axonal integrity of the visual system at different ages 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 : Four separate groups of D2 and B6 female mice underwent IOP and optokinetic assessments at the age of 5 (D2/B6, n=6/5), 7 (n=6/5), 9 (n=6/5) and 12 (n=13/4) months old (mos) using the TonoLab tonometer and OptoMotry system. Manganese(Mn)-enhanced MRI (MEMRI) of anterograde transport was then performed to a subset of mice (n=2-6 per age per D2/B6 group) in a 9.4-Tesla scanner at 8 hours after binocular intravitreal MnCl2 injection, and the remaining mice were sacrificed for immunohistochemistry of prechiasmatic optic nerve (ON) integrity.

Results : The IOP of D2 mice increased significantly at 9 mos and progressed further at 12 mos, whereas no apparent IOP difference was found in B6 mice across age (Fig. 1a). Visual acuity of D2 mice continued to worsen from 5 to 9 mos, whereas B6 mice performed better in optokinetics than D2 mice at each age (Fig. 1b). For MEMRI, Mn enhanced to similar extents along D2 and B6 visual pathways at 5 and 7 mos (white arrows in Fig. 1c). Reduced Mn enhancement began in the superior colliculus of D2 mice at 9 mos, and progressed further together with the ON and lateral geniculate nucleus at 12 mos (Fig. 1d); Neurofilament expression gradually decreased in ON of D2 mice from 5 to 12 mos, whereas pan-microglia and Tau expressions gradually increased in ON of D2 mice (Fig. 2). The axonal integrity in B6 mice appeared relatively comparable across age (Fig. 2).

Conclusions : Anterograde Mn transport along the visual pathway in D2 mice began to be disrupted at the onset of IOP increase at 9 mos and progressed further at 12 mos together with further IOP increase, neurofilament loss and elevated pan-microglia and Tau protein levels. Visual acuity in D2 mice appeared to deteriorate earlier than IOP increase and Mn transport disruption and was worse than B6 mice at every age, which suggested additional factors, such as gliosis, are contributing to the visuomotor deficits in D2 mice.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

 

 

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