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Abnormal metal levels in the primary visual pathway of the DBA/2J mouse model of glaucoma

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Abstract

The purpose of this study was to determine metal ion levels in central visual system structures of the DBA/2J mouse model of glaucoma. We used inductively coupled plasma mass spectrometry (ICP-MS) to measure levels of iron (Fe), copper (Cu), zinc (Zn), magnesium (Mg), manganese (Mn), and calcium (Ca) in the retina and retinal projection of 5-month (pre-glaucomatous) and 10-month (glaucomatous) old DBA/2J mice and age-matched C57BL/6J controls. We used microbeam X-ray fluorescence (μ-XRF) spectrometry to determine the spatial distribution of Fe, Zn, and Cu in the superior colliculus (SC), which is the major retinal target in rodents and one of the earliest sites of pathology in the DBA/2J mouse. Our ICP-MS experiments showed that glaucomatous DBA/2J had lower retinal Fe concentrations than pre-glaucomatous DBA/2J and age-matched C57BL/6J mice. Pre-glaucomatous DBA/2J retina had greater Mg, Ca, and Zn concentrations than glaucomatous DBA/2J and greater Mg and Ca than age-matched controls. Retinal Mn levels were significantly deficient in glaucomatous DBA/2J mice compared to aged-matched C57BL/6J and pre-glaucomatous DBA/2J mice. Regardless of age, the SC of C57BL/6J mice contained greater Fe, Mg, Mn, and Zn concentrations than the SC of DBA/2J mice. Greater Fe concentrations were measured by μ-XRF in both the superficial and deep SC of C57BL/6J mice than in DBA/2J mice. For the first time, we show direct measurement of metal concentrations in central visual system structures affected in glaucoma and present evidence for strain-related differences in metal content that may be specific to glaucomatous pathology.

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Acknowledgments

The acknowledgment can be added as follows “The authors would like to acknowledge Dr. Raul Barrea of Sector 18 (BIOCAT beamline) beamline support, Andrew Crawford for help with MatLab programming, and Kevin O’Neill for help with processing XRF images. The authors also thank Dr. Ted Huston for assistance with the ICP-MS samples. Use of the Advanced Photon Source, an Office of Science User Facility operated for the U.S. Department of Energy (DOE) Office of Science by Argonne National Laboratory, was supported by the U.S. DOE under Contract No. DE-AC02-06CH11357. This project was supported by Grants (9 P41 GM103622-18) from the National Institute of General Medical Sciences of the National Institutes of Health.

Funding

This work was supported by the following funding sources: The Ruth K. Broad Biomedical Foundation and the 2013 Research Fund (Project Number 1.130068.01) of UNIST (Ulsan National Institute of Science and Technology) (to M.H.L.). EY022358 from the National Eye Institute (to S.D.C.) NSF Graduate Research Fellowship (to A.S.D.).

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Author notes

  1. Cornelis J. van der Schyf

    Present address: Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, Graduate School, Idaho State University, Pocatello, ID, USA

Authors and Affiliations

  1. Department of Chemistry, University of Michigan, Ann Arbor, MI, 48109-1055, USA

    Alaina S. DeToma, Aniruddha Deb, Joseph J. Braymer, James E. Penner-Hahn & Mi Hee Lim

  2. Department of Pharmaceutical Sciences, Northeast Ohio Medical University (NEOMED), Rootstown, OH, USA

    Christine M. Dengler-Crish, Cornelis J. van der Schyf & Samuel D. Crish

  3. Michigan Memorial Phoenix Energy Institute, Ann Arbor, MI, USA

    Aniruddha Deb

  4. Biophysics, University of Michigan, Ann Arbor, MI, 48109-1055, USA

    James E. Penner-Hahn

  5. Life Sciences Institute, University of Michigan, Ann Arbor, MI, 48109-2216, USA

    Mi Hee Lim

  6. Department of Chemistry, Ulsan National Institute of Science and Technology (UNIST), Ulsan, 689-798, Korea

    Mi Hee Lim

Authors
  1. Alaina S. DeToma
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  2. Christine M. Dengler-Crish
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Correspondence to Mi Hee Lim or Samuel D. Crish.

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DeToma, A.S., Dengler-Crish, C.M., Deb, A. et al. Abnormal metal levels in the primary visual pathway of the DBA/2J mouse model of glaucoma. Biometals 27, 1291–1301 (2014). https://doi.org/10.1007/s10534-014-9790-z

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  • DOI: https://doi.org/10.1007/s10534-014-9790-z

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